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Adiponectin

Adiponectin is an adipokine, a 244-amino acid protein hormone (approximately 30 kDa in its monomeric form) primarily secreted by white adipose tissue, that regulates energy homeostasis by enhancing insulin sensitivity, promoting fatty acid oxidation, and exerting anti-inflammatory, anti-apoptotic, and anti-fibrotic effects across multiple organs including the liver, skeletal muscle, and vasculature.^[1] Discovered in 1995 through subtractive cloning of adipocyte-specific cDNAs by four independent research groups—including Philipp E. Scherer and colleagues, who identified it as a novel collagen-like serum protein akin to complement factor C1q—it was initially termed ACRP30, apM1, GBP28, or AdipoQ before being unified as adiponectin in 1999. Encoded by the ADIPOQ gene on human chromosome 3q27, a locus associated with type 2 diabetes susceptibility, adiponectin circulates in plasma at concentrations of 5–30 μg/mL in healthy adults, with levels exhibiting circadian rhythmicity (with a diurnal rhythm featuring a nocturnal decline) and sexual dimorphism (higher in females).^[2]^[3]^[4] Structurally, adiponectin comprises four distinct domains: an N-terminal signal peptide for secretion, a hypervariable region, a collagen-like domain facilitating multimerization, and a C-terminal globular domain homologous to C1q.^[1] Post-translational modifications, including disulfide bond formation and glycosylation, enable its assembly into bioactive oligomers—low-molecular-weight (LMW) trimers (~90 kDa), medium-molecular-weight (MMW) hexamers (~180 kDa), and high-molecular-weight (HMW) multimers (up to 630 kDa or larger)—with the HMW form demonstrating the highest potency in insulin-sensitizing and anti-diabetic activities.^[2] Its signaling is primarily transduced via two seven-transmembrane receptors, AdipoR1 (predominant in skeletal muscle, with high affinity for the globular isoform) and AdipoR2 (abundant in liver, preferring full-length multimers), which activate AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-alpha (PPAR-α), and other pathways to modulate glucose uptake, lipid catabolism, and inflammation; a third receptor, T-cadherin, binds HMW forms and contributes to cardioprotective effects in endothelial cells.^[1] In pathophysiology, adiponectin levels are inversely correlated with adiposity and metabolic dysfunction, being markedly reduced in obesity, insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, atherosclerosis, and certain malignancies such as breast and colorectal cancers, where it acts as a tumor suppressor by inhibiting cell proliferation and angiogenesis.^[2]^[3] Conversely, elevated levels are observed in conditions like cachexia or during caloric restriction, and hypoadiponectinemia serves as a biomarker for cardiovascular risk, with therapeutic interventions—such as thiazolidinedione drugs, exercise, or Mediterranean diets—increasing circulating adiponectin to mitigate these disorders.^[1] Ongoing research explores adiponectin mimetics and receptor agonists as potential treatments for metabolic syndrome and age-related diseases, given its preservation of metabolic fitness in centenarians.^[3]

Molecular Structure and Biochemistry

Protein Composition

Adiponectin is synthesized as a 244-amino-acid polypeptide precursor in adipocytes.^[5] This monomer features an N-terminal signal peptide spanning residues 1–22, which directs the protein to the secretory pathway and is cleaved upon export; a short variable region from residues 23–40; a central collagen-like domain encompassing residues 40–110 that enables triple helix formation; and a C-terminal globular domain from residues 110–244, structurally similar to the complement protein C1q.^[6]^[7] The mature monomer has an approximate molecular weight of 30 kDa and exhibits sequence homology to collagens VIII and X in its collagenous region, as well as to members of the tumor necrosis factor (TNF) family through its C1q-like globular domain.^[8] Post-translational modifications are critical to its stability and function, including hydroxylation and glycosylation at four conserved lysine residues (68, 71, 80, and 104) within the collagen-like domain, where lysine hydroxylation precedes the attachment of glucosylgalactosyl moieties.^[9]^[7] In human plasma, adiponectin circulates at concentrations typically ranging from 5 to 30 μg/mL, primarily existing in multimeric forms rather than as free monomers.^[10]

Oligomerization and Secretion

Adiponectin is synthesized as monomers that rapidly assemble into oligomeric complexes within the endoplasmic reticulum (ER) of adipocytes. The basic structural unit is the low-molecular-weight (LMW) trimer, formed through non-covalent interactions primarily involving the collagen-like domain, which adopts a triple-helical conformation similar to collagen fibers. These trimers can further associate to form medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) oligomers, typically comprising 12 to 18 monomers. The assembly into MMW and HMW forms is critically dependent on disulfide bonds, particularly those linking cysteine residues at position 36 (Cys36) in the N-terminal variable region of adjacent monomers or trimers. These covalent linkages stabilize the higher-order structures, while non-covalent interactions in the globular C-terminal domain and collagenous regions contribute to overall multimer stability. Disruption of these disulfide bonds, such as through Cys36 mutation, prevents hexamer and HMW formation, resulting in predominantly LMW trimers.^[11] Among the oligomeric forms, the HMW complex is the most biologically active, exerting potent insulin-sensitizing effects in peripheral tissues such as liver and skeletal muscle. Studies have shown that HMW adiponectin levels correlate more strongly with improved insulin sensitivity and reduced risk of type 2 diabetes compared to total adiponectin or other multimers, highlighting its superior efficacy in metabolic regulation. The formation of HMW oligomers requires not only disulfide bonding but also proper folding and quality control in the ER, where disulfide isomerase activity facilitates bond rearrangement to achieve the correct configuration. This process involves enzymes like protein disulfide isomerase (PDI) family members, which catalyze the formation, breakage, and reshuffling of disulfide bridges to promote stable multimerization.^[11]^[7] Secretion of adiponectin multimers occurs primarily from white adipose tissue (WAT), where mature adipocytes serve as the major source, accounting for over 90% of circulating levels. Lower levels of expression and secretion have been observed in brown adipose tissue (BAT) and the placenta, though these contribute minimally to systemic pools. The process is tightly regulated in the early secretory pathway, involving ER-to-Golgi transport and quality control mechanisms that ensure only properly assembled multimers are exported. A key regulator is the ER chaperone ERp44, a member of the PDI family, which binds to Cys36 in nascent adiponectin trimers via mixed disulfide bonds, retaining immature forms in the ER or cis-Golgi to prevent premature secretion. This retention is pH-dependent: at the neutral pH of the ER (approximately 7.2), ERp44 avidly binds substrates, while acidification in the cis-Golgi (pH around 6.7) promotes release, allowing mature HMW oligomers to proceed through the secretory pathway. Additionally, ERp44's isomerase activity aids in disulfide bond editing, facilitating the transition from LMW/MMW to HMW forms. Other factors, such as the oxidase Ero1α, can antagonize ERp44 retention by promoting disulfide transfer, thereby enhancing HMW secretion under physiological conditions.^[12]^[13]^[14]

Discovery and Genetics

Historical Identification

Adiponectin was first identified through independent cloning efforts in the mid-1990s as an adipose tissue-specific protein. In 1995, Scherer et al. cloned the mouse homolog, naming it Acrp30 (adipocyte complement-related protein of 30 kDa), based on its structural similarity to complement factor C1q and its exclusive expression in adipocytes.^[15] The following year, multiple groups reported the human cDNA: Maeda et al. described it as apM1 (adipose most abundant gene transcript 1), the most prevalent transcript in human adipose tissue; Hu et al. termed it AdipoQ; and Nakano et al. identified it as GBP28 (gelatin-binding protein of 28 kDa) after purifying it from human plasma via gelatin affinity chromatography.^[16]^[17] These early reports highlighted its collagen-like domain and secretion from adipocytes but did not yet elucidate its physiological role. In 1999, Arita et al. first used the name "adiponectin" and reported its paradoxical decrease in obesity, highlighting its potential metabolic role.^[18] Initial characterization revealed adiponectin as a circulating hormone with potential metabolic significance. In 2001, three independent studies demonstrated its insulin-sensitizing and anti-diabetic properties: Fruebis et al. showed that a globular fragment of adiponectin enhanced fatty acid oxidation and reduced body weight in mice; Berg et al. reported improved insulin action in liver and muscle; and Combs et al. observed dose-dependent effects on glucose uptake in adipocytes. By 2002, Maeda et al. generated adiponectin knockout mice, confirming its role in suppressing diabetes and atherosclerosis.^[19] Genome-wide linkage studies further linked adiponectin to metabolic disease susceptibility. In 2000, Vionnet et al. identified a type 2 diabetes susceptibility locus on chromosome 3q27 through a scan of French families.^[20] Subsequent association studies in 2002–2004 pinpointed the ADIPOQ gene (encoding adiponectin) within this locus, with variants correlating to lower plasma levels and increased risk of type 2 diabetes in Japanese and Pima Indian populations. These findings established adiponectin's genetic relevance early in its history.

Gene Localization and Regulation

The ADIPOQ gene, which encodes adiponectin, is located on the long arm of human chromosome 3 at the q27.3 locus.^[21] It spans approximately 16 kb of genomic DNA and consists of three exons, with two introns separating the coding regions.^[22] The promoter region of ADIPOQ contains specific response elements that facilitate binding of key transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding proteins (C/EBP), and sterol regulatory element-binding protein (SREBP).^[23] These elements enable coordinated regulation of gene expression in response to metabolic signals.^[24] Transcriptional regulation of ADIPOQ is tightly controlled by both positive and negative modulators. Upregulation occurs through activation by thiazolidinediones (TZDs), which are PPARγ agonists that enhance promoter activity and increase adiponectin expression in adipocytes.^[24] Similarly, caloric restriction promotes ADIPOQ transcription, leading to elevated adiponectin levels in adipose tissue and circulation, as observed in rodent models and human studies.^[25] In contrast, downregulation is mediated by proinflammatory and stress-related factors prevalent in obesity; tumor necrosis factor-alpha (TNF-α) suppresses ADIPOQ expression by inhibiting adipogenic transcription factors such as PPARγ and C/EBP.^[26] Glucocorticoids exert a similar inhibitory effect through suppression of these same regulators, while hypoxia in expanded adipose tissue reduces promoter activity via hypoxia-inducible factor-1 pathways.^[27] Certain single nucleotide polymorphisms (SNPs) in the ADIPOQ gene influence its expression and circulating adiponectin levels, contributing to metabolic disease susceptibility. The rs2241766 (T>G) variant in exon 2 is associated with altered plasma adiponectin concentrations and increased risk for conditions like type 2 diabetes and metabolic syndrome, particularly in certain ethnic populations.^[22] Likewise, the rs1501299 (G>T) polymorphism in intron 2 correlates with lower adiponectin levels and heightened metabolic risk, with the T allele showing stronger associations in obesity-related traits.^[28] These SNPs likely affect mRNA stability or transcription efficiency, though their precise mechanisms require further elucidation.^[29] ADIPOQ expression is predominantly restricted to adipose tissue, where it accounts for over 95% of total transcript levels, reflecting its role as an adipocyte-specific hormone.^[30] Low-level expression has been detected in other tissues, including liver and skeletal muscle, but these contribute minimally to systemic adiponectin production compared to adipocytes.^[31] This tissue specificity is maintained by the promoter's reliance on adipogenic factors like PPARγ and C/EBP, which are highly active in differentiated fat cells.^[23]

Physiological Functions

Glucose and Lipid Metabolism

Adiponectin enhances insulin sensitivity primarily by activating AMP-activated protein kinase (AMPK) in the liver and skeletal muscle, which promotes glucose uptake and utilization. In skeletal muscle, this activation leads to the translocation of glucose transporter 4 (GLUT4) to the cell membrane, facilitating increased glucose uptake independent of insulin stimulation. In the liver, adiponectin-mediated AMPK activation suppresses gluconeogenesis by inhibiting key enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), thereby reducing hepatic glucose output and contributing to lower blood glucose levels. Regarding lipid metabolism, adiponectin promotes fatty acid oxidation in skeletal muscle and liver through the sequential activation of AMPK, p38 mitogen-activated protein kinase (MAPK), and peroxisome proliferator-activated receptor alpha (PPARα), which upregulates carnitine palmitoyltransferase-1 (CPT-1) expression and activity. This pathway enhances the transport of fatty acids into mitochondria for β-oxidation, increasing energy expenditure from lipids. Additionally, AMPK activation by adiponectin leads to phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), reducing malonyl-CoA levels and thereby suppressing de novo lipogenesis while favoring fat catabolism. Adiponectin lowers circulating free fatty acids by inhibiting lipolysis in adipose tissue through AMPK activation, which suppresses hormone-sensitive lipase (HSL) activity, and by enhancing their oxidation in skeletal muscle and liver.^[32] It also promotes the clearance of circulating triglycerides by increasing lipoprotein lipase (LPL) activity, particularly in skeletal muscle.^[33]^[34] Animal models underscore these metabolic roles; adiponectin knockout mice exhibit exacerbated diet-induced insulin resistance, characterized by impaired glucose uptake and elevated hepatic glucose production upon high-fat feeding. Conversely, transgenic overexpression of adiponectin in mice protects against hyperglycemia and improves insulin sensitivity in models of diet-induced obesity, highlighting its essential function in maintaining carbohydrate and lipid homeostasis. These effects are mediated through adiponectin receptor signaling that activates AMPK, as detailed in receptor studies.

Anti-Inflammatory and Vascular Effects

Adiponectin exerts potent anti-inflammatory effects primarily through its actions on macrophages, where it suppresses the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). This suppression occurs via inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway, which is a key regulator of inflammatory responses in immune cells.^[35]^[36] Additionally, adiponectin promotes the expression of anti-inflammatory cytokines like interleukin-10 (IL-10), thereby shifting the immune balance toward resolution of inflammation.^[37] These immunomodulatory properties are mediated in part through activation of AMP-activated protein kinase (AMPK), which overlaps with its metabolic roles but distinctly targets inflammatory cascades in macrophages.^[36] In the vascular system, adiponectin provides protective effects on the endothelium by reducing the expression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), which diminishes monocyte attachment and infiltration into the vessel wall.^[38] This anti-adhesive action helps prevent the initiation of inflammatory processes in the vasculature. Furthermore, adiponectin enhances nitric oxide (NO) production through activation of endothelial nitric oxide synthase (eNOS), promoting vasodilation and maintaining endothelial integrity.^[39] These mechanisms collectively contribute to the preservation of vascular homeostasis and reduced endothelial dysfunction. Adiponectin's anti-atherogenic effects are evident in its promotion of cholesterol efflux from macrophages, facilitating the removal of excess lipids and preventing foam cell formation in atherosclerotic lesions.^[40] It achieves this by upregulating ATP-binding cassette transporter A1 (ABCA1), a key mediator of reverse cholesterol transport. Additionally, adiponectin improves high-density lipoprotein (HDL) functionality, enhancing its capacity for cholesterol acceptance and transport, which further mitigates plaque development.^[41] Beyond inflammation and atherosclerosis, adiponectin supports wound healing and tissue repair by reducing ceramide levels through stimulation of ceramidase activity associated with its receptors, AdipoR1 and AdipoR2.^[42] This ceramide-lowering effect inhibits apoptosis in endothelial cells, preserving cellular viability during injury and promoting regenerative processes.^[43] Overall, these actions position adiponectin as a multifaceted protector of vascular and tissue integrity.^[44]

Receptors and Signaling

Receptor Types and Tissue Distribution

AdipoR1 and AdipoR2 are the principal receptors for adiponectin, identified through expression cloning in mammalian cells. Both are integral membrane proteins featuring seven transmembrane domains, but they differ from G-protein-coupled receptors in their topology, with an amino-terminal cytoplasmic domain and a carboxy-terminal extracellular domain.^[45]^[8] AdipoR1 exhibits high affinity for globular adiponectin, a proteolytic fragment of the full-length protein, while AdipoR2 displays moderate affinity for both globular and full-length forms, with a preference for the latter. AdipoR1 is predominantly expressed in skeletal muscle, where it accounts for the majority of adiponectin binding, whereas AdipoR2 is primarily found in the liver.^[45]^[46]^[47] Beyond skeletal muscle and liver, AdipoR1 is also expressed at lower levels in the liver, brain, and endothelial cells, while AdipoR2 shows higher expression in hepatocytes compared to other hepatic cell types. AdipoR1 and AdipoR2 are constitutively expressed across various tissues, including adipose tissue, heart, and kidney, but their levels can vary with physiological conditions.^[48]^[49] Additional adiponectin-binding proteins function as receptors for specific oligomeric forms or in clearance mechanisms. T-cadherin, a glycosylphosphatidylinositol-anchored protein, selectively binds high-molecular-weight adiponectin multimers and is highly expressed in the heart and vascular endothelium. The calreticulin/CD91 complex, involving the chaperone calreticulin and low-density lipoprotein receptor-related protein 1 (CD91), mediates adiponectin-dependent uptake of apoptotic cells and is involved in its clearance, primarily in macrophages.^[50]^[51]^[52] The genes encoding AdipoR1 (ADIPOR1) and AdipoR2 (ADIPOR2) are located on human chromosomes 1q32.1 and 12p13.33, respectively. Their expression is upregulated by exercise training, which increases AdipoR1 and AdipoR2 mRNA levels in skeletal muscle and peripheral blood mononuclear cells. In the liver, fibrates such as fenofibrate can enhance AdipoR2 expression in hepatocytes.^[53]^[54]^[55]^[56]

Intracellular Pathways

Upon binding to its receptors AdipoR1 and AdipoR2, adiponectin recruits the adaptor protein APPL1, which facilitates the activation of AMP-activated protein kinase (AMPK) through upstream kinases such as liver kinase B1 (LKB1) and Ca²⁺/calmodulin-dependent protein kinase kinase β (CaMKKβ).^[57]^[58] This recruitment promotes the cytosolic translocation of LKB1, enabling its phosphorylation and subsequent AMPK activation, particularly in muscle and liver cells.^[57] In parallel, Ca²⁺ influx triggered by adiponectin enhances CaMKKβ activity, leading to LKB1 phosphorylation at Ser431 and further amplification of the AMPK pathway.^[58] Activated AMPK by adiponectin signaling stimulates peroxisome proliferator-activated receptor α (PPARα) and sirtuin 1 (SIRT1) pathways, promoting fatty acid oxidation and mitochondrial biogenesis in metabolically active tissues.^[59] Specifically, SIRT1 deacetylates and activates PPARα, enhancing expression of genes involved in β-oxidation, while also cooperating with PGC-1α to drive mitochondrial function.^[59] Additionally, adiponectin inhibits c-Jun N-terminal kinase (JNK) and inhibitor of κB kinase β (IKKβ) activation, thereby suppressing pro-inflammatory and pro-apoptotic signals to confer cytoprotective effects.^[60] Adiponectin also reduces intracellular ceramide levels by stimulating ceramidase activity intrinsic to AdipoR1 and AdipoR2, which hydrolyzes ceramides into sphingosine and fatty acids, thereby alleviating lipid-induced insulin resistance.^[42] This ceramidase activation lowers ceramide accumulation in cells exposed to saturated fatty acids, improving insulin sensitivity without altering ceramide synthesis rates.^[42] Beyond these canonical routes, adiponectin engages non-canonical pathways, including mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling to promote cell proliferation in contexts such as neural stem cells and osteoblasts.^[61]^[62] Furthermore, APPL1 serves as a mediator for crosstalk between adiponectin and insulin signaling, enhancing insulin receptor substrate-1 phosphorylation and amplifying insulin's metabolic actions in skeletal muscle.^[63]

Clinical Relevance

Hypoadiponectinemia in Metabolic Disorders

Hypoadiponectinemia, characterized by circulating adiponectin levels below 5 μg/mL, is commonly observed in conditions such as obesity, type 2 diabetes, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). In obese individuals, low adiponectin concentrations are inversely correlated with body mass index and insulin resistance, with prevalence rates reaching up to 57% in men and 32% in women exhibiting metabolic syndrome features. This deficiency is particularly linked to visceral fat accumulation, which promotes insulin resistance and hepatic steatosis in NAFLD by impairing glucose and lipid metabolism regulation.^[64]^[65]^[66]^[67] The underlying mechanisms of hypoadiponectinemia involve adipose tissue dysfunction, where chronic inflammation suppresses ADIPOQ gene transcription. Pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), inhibit adiponectin expression at the transcriptional level in adipocytes, exacerbating metabolic dysregulation. Additionally, endoplasmic reticulum (ER) stress in obese adipose tissue impairs the proper folding and multimerization of adiponectin multimers, reducing its secretion and bioavailability, which further contributes to insulin resistance and lipid accumulation.^[68]^[69]^[70] Genetic factors also play a role, with variants like the +45T>G single nucleotide polymorphism (SNP) in the ADIPOQ gene associated with lower circulating adiponectin levels and heightened diabetes susceptibility. Carriers of the G allele exhibit reduced adiponectin concentrations and face an approximately 1.8-fold increased odds ratio for developing type 2 diabetes compared to those with the TT genotype. This SNP influences adiponectin production, amplifying risks in the context of visceral obesity and metabolic syndrome.^[71]^[72] Lifestyle and pharmacological interventions can elevate adiponectin levels, mitigating associated metabolic impairments. Weight loss through caloric restriction has been shown to increase plasma adiponectin by up to 75%, correlating with reduced insulin resistance as assessed by HOMA-IR. Similarly, thiazolidinedione (TZD) therapy, such as with troglitazone, raises adiponectin levels approximately 2-fold, improving glucose disposal rates and HOMA-IR in patients with type 2 diabetes.^[73]^[74]

Associations with Other Diseases

Adiponectin exhibits a protective role in cardiovascular disease (CVD), with low circulating levels serving as an independent predictor of atherosclerosis progression and incident heart failure. In prospective cohort studies, hypoadiponectinemia has been linked to a heightened risk of coronary events, where each standard deviation decrease in adiponectin concentration correlates with approximately a 20-30% increased relative risk of adverse outcomes, including a relative risk of about 1.4 for heart failure per 50% reduction in levels. This protective effect is mediated through adiponectin's suppression of endothelial inflammation and oxidative stress, thereby inhibiting plaque formation and vascular remodeling.^[75]^[76]^[77] Beyond CVD, adiponectin demonstrates associations with several non-metabolic conditions, particularly those involving inflammation and neurodegeneration. In rheumatoid arthritis (RA), higher adiponectin levels correlate with reduced disease activity and lower Sharp/van der Heijde scores for joint damage, attributed to its anti-inflammatory modulation of synovial cytokine production and inhibition of matrix metalloproteinases. Similarly, lower serum adiponectin in attention-deficit/hyperactivity disorder (ADHD) patients is inversely related to symptom severity, potentially via impaired hippocampal neurogenesis, as adiponectin signaling through AdipoR1 promotes neuronal proliferation and synaptic plasticity in preclinical models. During the COVID-19 pandemic, studies from 2021-2023 revealed an inverse correlation between adiponectin levels and disease severity, with reduced concentrations in patients experiencing acute respiratory failure and cytokine storms, suggesting adiponectin's role in mitigating hyperinflammation.^[78]^[79]^[80]^[81]^[82]^[83] Emerging research from 2024-2025 highlights adiponectin's involvement in aging and related pathologies. Activation of AdipoR1 by adiponectin or its agonists, such as AdipoRon, has been shown to enhance mitochondrial function and reduce age-associated inflammation in mouse models of retinal aging, promoting tissue-specific healthspan through AMPK-dependent pathways. In prediabetes, elevated adiponectin levels act protectively by improving insulin sensitivity and suppressing hepatic gluconeogenesis, potentially delaying progression to overt diabetes. For osteoporosis, adiponectin influences bone remodeling by inhibiting osteoclastogenesis and supporting osteoblast survival via AdipoR1 signaling, with recent studies indicating that receptor agonism mitigates age-related bone loss in diabetic models.^[84]^[85]^[86]^[87]^[88] Adiponectin's effects in cancer present a paradoxical profile, varying by tumor type and multimer form. High-molecular-weight multimers predominate in protective associations, where elevated total adiponectin levels reduce risk in breast and colorectal cancers by suppressing tumor cell proliferation through AMPK activation and anti-angiogenic effects. Conversely, in certain malignancies like endometrial or prostate cancer, lower adiponectin or specific low-molecular-weight forms may promote progression via enhanced inflammatory signaling or altered receptor affinity, underscoring the need for multimer-specific assessments in oncology.^[89]^[90]^[91]^[92]

Therapeutic Applications

Biomarker Utility

Adiponectin levels in plasma are commonly measured using enzyme-linked immunosorbent assay (ELISA) kits, which detect total adiponectin or specific multimers with high sensitivity (typically 0.01–0.4 ng/mL) and low coefficients of variation (intra-assay CV ~4–5%, inter-assay CV ~6–12%).^[93]^[94] Among the oligomeric forms, high-molecular-weight (HMW) adiponectin multimers are the most predictive of insulin sensitivity, outperforming total adiponectin as a marker of insulin resistance due to their predominant biological activity in metabolic regulation.^[95] Low HMW adiponectin levels, often below 4 μg/mL, indicate increased risk for metabolic disturbances, with cutoffs such as 2.75–4.2 μg/mL used to diagnose insulin resistance in clinical studies.^[96]^[97] As a prognostic biomarker, low circulating adiponectin forecasts the onset of type 2 diabetes (T2D), with baseline levels inversely associated with disease risk independent of obesity and inflammation; for instance, levels below 7.5 μg/mL total adiponectin yield an area under the curve (AUC) of 0.74 for T2D prediction, alongside odds ratios of 0.88 (95% CI: 0.80–0.96).^[93]^[98] It also monitors responses to lifestyle interventions, where increases in adiponectin (often 20–30% post-weight loss) correlate with improved insulin sensitivity and reduced inflammation, regardless of absolute weight change.^[99] Recent 2023 studies have integrated adiponectin ratios (e.g., growth differentiation factor-15/adiponectin) into metabolic syndrome scoring systems for enhanced detection, particularly in high-risk populations. In prediabetes screening, adiponectin demonstrates utility with AUC values around 0.80–0.87 for predicting progression to T2D, serving as an adjunct to standard glycemic assessments.^[100]^[101] Despite these applications, limitations include diurnal variations in HMW adiponectin (up to 20–30% day/night fluctuations), which may affect timing of measurements, and assay variability across commercial ELISA kits due to differences in antibody specificity for multimers.^[102]^[103] Adiponectin alone is not superior to HbA1c for T2D screening or monitoring, though combining it with HbA1c improves predictive AUC by ~0.06, highlighting its role as a complementary rather than standalone marker.^[104]^[105]

Drug Targets and Developments

Pharmacological strategies to modulate adiponectin signaling have focused on direct activation of its receptors, administration of recombinant forms, and indirect enhancement of endogenous levels. AdipoRon, a small-molecule agonist of adiponectin receptors AdipoR1 and AdipoR2, activates AMP-activated protein kinase (AMPK) and has demonstrated preclinical efficacy in improving insulin sensitivity and ameliorating type 2 diabetes in obese mouse models.^[106] Peptide mimetics such as ALY688, an adiponectin receptor agonist, have been evaluated in 2024 studies for target engagement, enabling non-invasive bioassays to monitor adiponectin signaling in peripheral tissues like blood samples from treated mice.^[107] Recombinant adiponectin formulations have been explored for therapeutic potential in metabolic disorders, though clinical advancement has been limited by pharmacokinetic challenges. Early-phase investigations, including preclinical and initial human studies prior to 2020, suggested improvements in insulin sensitivity for conditions like non-alcoholic fatty liver disease (NAFLD) and obesity, with reported enhancements of up to 20-30% in insulin-responsive tissues in animal models; however, no active Phase I/II trials were registered between 2022 and 2025 on ClinicalTrials.gov for these indications.^[108] Indirect approaches to elevate adiponectin levels include approved antidiabetic agents and emerging genetic interventions. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as exenatide and semaglutide, increase circulating adiponectin concentrations, with clinical studies showing significant elevations (e.g., up to 193% with combined exenatide and pioglitazone therapy) alongside improvements in glucose metabolism and reduced inflammation in type 2 diabetes patients.^[109] Similarly, sodium-glucose cotransporter 2 (SGLT2) inhibitors like dapagliflozin and empagliflozin boost plasma adiponectin levels, as evidenced by meta-analyses and randomized trials reporting increases associated with enhanced adipose tissue function and reduced leptin in obese individuals with diabetes.^[110] Gene therapy targeting the ADIPOQ promoter to upregulate adiponectin expression has shown promise in preclinical models of obesity and high-fat diet-induced insulin resistance, with recent 2025 reviews highlighting its potential as an innovative strategy for sustained elevation of adiponectin to counteract metabolic dysfunction.^[111]^[112] Key challenges in adiponectin-based therapies include its short plasma half-life of approximately 30-75 minutes following intravenous administration, primarily due to hepatic clearance, which complicates dosing and efficacy in clinical settings.^[113] In the 2025 obesity treatment landscape, combination therapies incorporating adiponectin-modulating agents with GLP-1 agonists like semaglutide are gaining attention; for instance, semaglutide monotherapy elevates adiponectin levels while promoting weight loss, suggesting synergistic potential in addressing hypoadiponectinemia without direct recombinant use.^[114]

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TNFα can inhibit adiponectin expression by suppressing the expression of adipogenic transcription factors including PPARγ, C/EBP, and SREBP, while IL-6 and IL- ...
[24]
Emerging Role of Adipose Tissue Hypoxia in Obesity and Insulin ...
The gene promoter activity of adiponectin was reduced by hypoxia and TNF-α (20, 21, 46). It remains to be investigated how the promoter was down-regulated by ...
[25]
Associations between polymorphisms of the ADIPOQ gene and ...
Feb 9, 2017 · In conclusion, the rs2241766 polymorphism was found to be associated with a significant increase in hypertension risk based on our analysis.
[26]
Association of rs2241766 and rs1501299 polymorphisms in the ...
The genotypes of the rs2241766 T/G and rs1501299 G/T polymorphism were significantly associated with serum APN levels in MetS patients. The ADIPOQ polymorphisms ...
[27]
AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity
Aug 22, 1995 · The expression of adipoQ is highly specific to adipose tissue in both mouse and rat. Expression of adipoQ is observed exclusively in mature fat ...<|control11|><|separator|>
[28]
ADIPOQ protein expression summary - The Human Protein Atlas
Gene name i. Official gene symbol, which is typically a short form of the gene name, according to HGNC. ADIPOQ (ACDC, ACRP30, adiponectin, apM1, GBP28).
[29]
Adiponectin Increases Fatty Acid Oxidation in Skeletal Muscle Cells ...
Treatment with adiponectin or ectopic expression of its receptors has been shown to increase AMPK phosphorylation and fatty acid oxidation in muscles, and this ...Missing: et | Show results with:et
[30]
Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines ...
Aug 23, 2021 · Adiponectin inhibits the production of TNF-α, IL-6 and chemokines by human lung macrophages. Hélène Salvator
[31]
Adiponectin Inhibits Pro-inflammatory Signaling in Human ... - NIH
Adiponectin, a vasculoprotective molecule with insulin-sensitizing and anti-atherogenic properties, suppresses pro-inflammatory gene expression in macrophages.
[32]
Harnessing adiponectin for sepsis: current knowledge, clinical ...
Jul 12, 2025 · Beyond immune regulation, adiponectin exerts protective vascular effects by decreasing endothelial expression of adhesion molecules such as ICAM ...Missing: seminal papers
[33]
Globular adiponectin counteracts VCAM-1-mediated monocyte ...
At the endothelial level, Ad stimulates nitric oxide (NO) production following activation of phosphatidylinositol 3-kinase (PI3K) and AMP-activated protein ...Missing: ICAM- attachment
[34]
Adiponectin resistance and vascular dysfunction in the ... - Nature
Aug 30, 2010 · Interestingly, APN exerts anti-inflammatory and anti-atherogenic properties via its ability to stimulate vascular endothelial NO production.Apn In Vascular Physiology... · Role Of Apn In Metabolic And... · Vascular Dysfunction In...Missing: seminal papers
[35]
Adiponectin prevents atherosclerosis by increasing cholesterol ...
Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages ... HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia.
[36]
The role of adiponectin in cholesterol efflux and HDL biogenesis ...
Adiponectin plays a key role in promoting ABCA1-dependent cholesterol efflux and in modulating HDL biogenesis via activation of the PPAR-γ/LXR-α signalling ...
[37]
The Pleiotropic Actions of Adiponectin are Initiated via Receptor ...
Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, adipoR1 and adipoR2, and enhances ceramide ...Adiponectin Lowers Ceramide... · Fig 1. Adiponectin Rapidly... · Fig 4. Adiponectin Alters...Missing: wound healing repair<|control11|><|separator|>
[38]
Adiponectin controls the apoptosis and the expression of tight ...
Oct 12, 2017 · One study showed that adiponectin prevents the inflammation of vascular endothelial cells by reducing the secretion of ROS. Considering ...Missing: wound healing repair
[39]
Adiponectin as a tissue regenerating hormone - PubMed Central - NIH
Adiponectin has insulin-sensitizing action and leads to down-regulation of hepatic gluconeogenesis and an increase of fatty acid oxidation. In addition, ...
[40]
Cloning of adiponectin receptors that mediate antidiabetic metabolic ...
Jun 12, 2003 · Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Toshimasa Yamauchi,; Junji Kamon,; Yusuke Ito ...
[41]
Adiponectin and adiponectin receptors in insulin resistance ... - JCI
Jul 3, 2006 · Thus, HMW adiponectin level may be the superior biomarker for insulin resistance, the metabolic syndrome, and type 2 diabetes. Cloning, function ...
[42]
Adiponectin Receptor - an overview | ScienceDirect Topics
AdipoR1 expression is highly abundant in skeletal muscle and serves as a high-affinity receptor for globular adiponectin, whereas AdipoR2 expression is highest ...
[43]
Divergent Roles for Adiponectin Receptor 1 (AdipoR1) and AdipoR2 ...
A distribution analysis was performed for AdipoR1 and AdipoR2 mRNA expression in vascular and metabolically important mouse tissues. AdipoR1 is abundant in ...
[44]
Adiponectin: Structure, Physiological Functions, Role in Diseases ...
A full-length adiponectin (~30 kDa) consists of a globular domain, a collagenous domain, a species-specific domain, and a signal peptide. Oligomerization ...Adiponectin: Structure... · 4. Adiponectin Functions In... · 5. Adiponectin And Diseases
[45]
Native adiponectin in serum binds to mammalian cells expressing T ...
Oct 24, 2019 · Adiponectin is a circulating factor that is secreted from adipocytes (Hu et al., 1996; Maeda et al., 1996; Nakano et al., 1996; Scherer et al., ...
[46]
Adiponectin/AdipoR Research and Its Implications for Lifestyle ... - NIH
Aug 14, 2019 · This review is intended to highlight some milestones in adipocyte research from the discovery of the insulin-sensitizing properties of adiponectin.Role Of Adipokines In... · Signal Transduction... · Adipor Agonists In...
[47]
C1q/TNF-Related Proteins, A Family of Novel Adipokines, Induce ...
Aug 11, 2011 · Two APN receptors, AdipoR1 and AdipoR2, have been cloned, and several putative cell surface molecules, including T-cadherin and calreticulin/ ...
[48]
Gene ResultADIPOR1 adiponectin receptor 1 [ (human)] - NCBI
Sep 13, 2025 · A pseudogene of this gene is located on chromosome 14. Multiple ... SNPs of both the adiponectin gene and its receptors AdipoR1 and AdipoR2 ...
[49]
Entry - *607946 - ADIPONECTIN RECEPTOR 2; ADIPOR2 - OMIM
Mapping. Yamauchi et al. (2003) stated that the human ADIPOR2 gene maps to chromosome 12p13. 31 and the mouse Adipor2 gene maps to chromosome 6F1.
[50]
[PDF] Effect of Exercise Training on Adiponectin Receptor Expression and ...
Exercise training for 4 weeks resulted in a significant improvement in the insulin resistance state, significant increase in expression of AdipoR1 and AdipoR2 ...<|control11|><|separator|>
[51]
Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin ...
Adiponectin receptors play a key role in steatosis and inflammation; however, very little is known about regulation of adiponectin receptors in liver.
[52]
Adiponectin Activates AMP-activated Protein Kinase in Muscle Cells ...
Here we show that in muscle cells adiponectin and metformin induce AMPK activation by promoting APPL1-dependent LKB1 cytosolic translocation.
[53]
Mechanisms of Adiponectin Action - NIH
Apr 10, 2019 · In vitro studies confirmed that AdipoRon increased the intracellular Ca2+ influx that activated the CaMKKβ/phosphorylated Ser431LKB1/ ...
[54]
Involvement of adiponectin-SIRT1-AMPK signaling in the protective ...
Two major adiponectin receptors (AdipoR1 and -R2) serve as transducers of adiponectin-mediated signaling, leading to increased fatty acid oxidation and reduced ...<|control11|><|separator|>
[55]
Adiponectin Inhibits NLRP3 Inflammasome Activation in ... - Frontiers
Furthermore, the results showed that the inhibitory effect of adiponectin on PA-mediated inflammasome activation was regulated by AMPK-JNK/ErK1/2-NFκB/ROS ...
[56]
Adiponectin Stimulates Proliferation of Adult Hippocampal Neural ...
Adiponectin stimulates proliferation of hippocampal neural stem/progenitor cells in vitro and activates the p38MAPK/GSK-3β/β-catenin signaling pathway.
[57]
Adiponectin and AMP kinase activator stimulate proliferation ...
Nov 29, 2007 · In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 ...
[58]
The Role of Leptin and Adiponectin in Obesity-Associated Cognitive ...
Activation of AdipoRs by adiponectin leads to the recruitment of the adaptor protein APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and ...Adipokines In Obesity And... · Adiponectin · Leptin<|control11|><|separator|>
[59]
Hypoadiponectinemia in Obesity: Association with Insulin Resistance
Hypoadiponectinemia has been demonstrated to be linked with insulin resistance [5], while increased adiponectin levels by supplementation of adiponectin ...
[60]
Hypoadiponectinemia | Hypertension
More frequently, low adiponectin levels arise from a positive energy balance and an expansion of visceral fat (secondary hypoadiponectinemia), which are related ...Missing: NAFLD | Show results with:NAFLD
[61]
Hypoadiponectinemia Is Strongly Associated with Metabolic ...
Results: The prevalence of hypoadiponectinemia (<4.0 µg/mL) was 57.4% in men and 32.4% in women. Serum adiponectin level was negatively correlated with body ...<|control11|><|separator|>
[62]
Plasma Adiponectin in Nonalcoholic Fatty Liver Is Related to ...
The results demonstrate that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the amount of hepatic fat ...
[63]
Adiponectin as an anti-inflammatory factor - PMC - NIH
Pro-inflammatory cytokines suppress adiponectin expression in adipocytes. TNF-α treatment suppresses adiponectin expression at the level of transcription in ...Adiponectin As An... · 2. Experimental Data · 3.3 Adiponectin And...
[64]
Effect of Endoplasmic Reticulum Stress on Inflammation and ...
The data suggest that ER stress modifies adiponectin secretion and induces inflammation in ADHAS cells.Missing: ERdj3 | Show results with:ERdj3
[65]
ER stress in adipocytes and insulin resistance
Sep 3, 2014 · This review demonstrates the existence of a strong association between adipocyte ER stress and IR that is complex and multifactorial.
[66]
The adiponectin gene is associated with adiponectin levels but not ...
Jan 18, 2006 · The common T-allele (88.5%) of SNP +45T>G and the common G-allele (70.5%) of SNP +276G>T were associated with significantly lower serum ...Missing: percentage | Show results with:percentage
[67]
An SNP in the Adiponectin Gene Is Associated with Decreased ...
Sep 6, 2012 · Carriers of the G allele at position 45 had higher odds ratio (OR) for IGT [OR, 1.65; 95% confidence interval (CI), 1.08 to 2.51; p = 0.020] ...
[68]
Effect of Marked Weight Loss on Adiponectin Gene Expression and ...
Sep 6, 2012 · Weight loss resulted in an ∼75% increase in total plasma adiponectin concentrations in our subjects. The change in circulating adiponectin was ...
[69]
The Effect of Thiazolidinediones on Plasma Adiponectin Levels in ...
Oct 1, 2002 · Our findings show that TZD treatment increased adiponectin levels in all subjects, including normal subjects in which no other effects of TZDs ...
[70]
Estimated Glomerular Filtration Rate and Incident Prediabetes Risk ...
Oct 11, 2025 · ... progression to prediabetes [HR 0.986 (95% CI 0.975-0.997)]. In other ... Adiponectin levels predict prediabetes risk: the Pathobiology ...
[71]
Cardioprotection by Adiponectin - PMC - NIH
In heart, adiponectin serves as a regulator of cardiac injury through modulation of anti-inflammatory and prosurvival reactions, and it also functions to ...Role Of Adiponectin In... · Adiponectin And Hypertrophic... · Adiponectin And Myocardial...
[72]
Association of serum adiponectin with risk for cardiovascular events ...
Lower levels of serum adiponectin were significantly associated with an increased risk for future non-fatal cardiovascular events in men with symptomatic PAD, ...
[73]
Adiponectin: a key adipocytokine in metabolic syndrome
Accumulating experimental evidence indicates that adiponectin possesses anti-atherogenic, anti-inflammatory and anti-diabetic properties.Missing: original | Show results with:original
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Adiponectin is negatively associated with disease activity and Sharp ...
Feb 8, 2022 · Increased adiponectin is negatively linked to the local inflammatory process in patients with rheumatoid arthritis. Cytokine 35(5), 247–252 ( ...
[75]
Adiponectin exerts a potent anti‐arthritic effect and insulin resistance ...
Jul 27, 2017 · Conclusions. Adiponectin might display anti-inflammatory effects. These results suggest that AD may be a potential immunosuppressant for the ...
[76]
Decreased serum levels of adiponectin in adult attention deficit ...
Apr 30, 2014 · This study shows that ADHD patients have decreased serum adiponectin levels, which are inversely correlated to psychiatric symptoms.
[77]
Fat cell-secreted adiponectin mediates physical exercise-induced ...
Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin. Proc Natl Acad Sci U S A ...Missing: ADHD | Show results with:ADHD
[78]
Reduced adiponectin levels in patients with COVID‐19 acute ... - NIH
Adiponectin levels were significantly lower in patients with COVID‐19 respiratory failure, even after adjustment for age, sex, BMI, and other covariates.Missing: 2022 2023<|control11|><|separator|>
[79]
Circulating adipokine levels and COVID-19 severity in hospitalized ...
Dec 12, 2022 · In severe COVID-19 patients, IL-6 levels positively correlated with the levels of Adiponectin, Visfatin, Resistin and negatively correlated ...Missing: inverse | Show results with:inverse
[80]
Heterochronic parabiosis uncovers AdipoR1 as a critical player in ...
Jul 16, 2025 · Mechanistically, AdipoR1-AMPK activation promoted mitochondrial function, contributing to the restoration of youthful cellular phenotypes.
[81]
(PDF) Adiponectin/adiponectin receptor in disease and aging
Aug 10, 2025 · Adiponectin has also recently been shown to regulate longevity signaling thus prolonging lifespan. Therefore, the strategy for activating ...
[82]
Therapeutic potential of adiponectin in prediabetes - PubMed Central
Jan 18, 2024 · Low adiponectin concentrations have been associated with elevated fasting glucose, increased insulin resistance, and impaired glucose tolerance, ...Missing: hazard | Show results with:hazard
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Therapeutic potential of adiponectin in prediabetes - Sage Journals
This review examines the therapeutic potential of adiponectin in managing prediabetes, elucidating on multiple aspects including its role in glucose and lipid ...Missing: hazard | Show results with:hazard
[84]
Aging alters the effect of adiponectin receptor signaling on bone ...
Oct 27, 2024 · Adiponectin receptor signaling represents a promising therapeutic target for age-related conditions such as osteoporosis and diabetes.Missing: prediabetes | Show results with:prediabetes
[85]
Aging alters the effect of adiponectin receptor signaling on bone ...
Adiponectin receptor signaling represents a promising therapeutic target for age‐related conditions such as osteoporosis and diabetes.2. Results · 2.1. Aged Mice Showed Lower... · 2.8. The Ar1‐wnt Pathway...
[86]
The Role of Adiponectin in Cancer: A Review of Current Evidence
APPL-1 also acts in the insulin-signaling pathway, playing a pivotal role in the cross talk between adiponectin/insulin-signaling pathways (105). Finally ...
[87]
Adiponectin, Obesity, and Cancer: Clash of the Bigwigs in Health ...
Increase in visceral fat mass lowers systemic adiponectin levels creating insulin resistance in the skeletal muscle while glucose signaling in response to food ...Adiponectin, Obesity, And... · 6. Adiponectin- And... · 8. Adiponectin Orchestrates...Missing: doubles | Show results with:doubles
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Role of Adiponectin and Its Receptors in Cancer
Dec 1, 2012 · Adiponectin and Cancer. Circulating plasma concentrations of APN are inversely related to increased risks of malignancy. Studies have shown ...Adiponectin And Cancer · Breast Cancer · Footnotes
[89]
Multifaceted roles of Adiponectin in cancer - PMC - PubMed Central
In obesity, decreased Adiponectin plasma levels correlate with tumor development and progression. The association of Adiponectin with potential tumor-limiting ...Roles Of Adiponectin In... · Adiponectin-Activated... · Ampk Activation By...<|control11|><|separator|>
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Clinical Applications of Adiponectin Measurements in Type 2 ...
Jul 5, 2018 · Adiponectin levels are associated with better glycemic control and could be a useful adjunct for screening for IR and T2DM. Therapeutic measures ...<|separator|>
[91]
Human Adiponectin ELISA Kit (BMS2032-2) - Invitrogen
6–10 day deliveryQuantify human Adiponectin in plasma, serum and supernatant. Sensitivity: 0.012 ng/mL. Hands-on time: 1 Hr. 20 Min. Assay Range: 0.23-15 ng/mL.
[92]
Total and high molecular weight adiponectin have similar utility for ...
Jun 23, 2010 · High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The ...
[93]
Measurement of the High–Molecular Weight Form of Adiponectin in ...
Jun 1, 2006 · There is a mounting body of evidence to suggest that adiponectin is an insulin-sensitizing hormone and that the plasma level of this hormone is ...
[94]
Total and high-molecular-weight adiponectin levels and prediction ...
Jun 4, 2018 · Total and high molecular weight adiponectin and ethnic-specific differences in adiposity and insulin resistance: a cross-sectional study.
[95]
Adiponectin Levels and Risk of Type 2 Diabetes - JAMA Network
Jul 8, 2009 · Higher adiponectin levels are associated with a lower risk of type 2 diabetes across diverse populations, consistent with a dose-response relationship.
[96]
Assessment of adiponectin and leptin as biomarkers of ... - PubMed
Conclusions: After lifestyle intervention, adiponectin increased regardless of changes in weight, whereas no consistent changes was observed in serum leptin.
[97]
Adiponectin, IGFBP-1 and -2 are independent predictors ... - PubMed
Jan 5, 2023 · Adiponectin, IGFBP-1 and -2 are independent predictors in forecasting prediabetes and type 2 diabetes ... AUC reached 0.87 for women and ...<|separator|>
[98]
Adiponectin levels predict prediabetes risk: the Pathobiology of ...
Mar 17, 2016 · Adiponectin levels correlated inversely with adiposity and glycemia, and positively with insulin sensitivity and high-density lipoprotein ...Research Design And Methods · Insulin Sensitivity And... · Adiponectin And Progression...
[99]
Day/night variations of high-molecular-weight adiponectin and ...
Aug 12, 2010 · Adiponectin and lipocalin-2 are adipocyte-derived plasma proteins that have been proposed to have opposite effects on insulin sensitivity.
[100]
Comparison of two techniques of adiponectin assay, ELISA and ...
Intra-assay coefficients of variability (CVs; n = 30) were 5.0% and 1.6%, and interassay CVs (n = 32) were 12.3% and 3.7% for IQC levels 2 and 3 ...
[101]
Plasma adiponectin levels and type 2 diabetes risk: a nested case ...
Jan 10, 2018 · In addition, a T2D score comprising adiponectin and other five biomarkers has shown better predictive utility (assessed by AUC) than HbA1c and ...
[102]
Association between adiponectin and newly diagnosed ... - BMJ Open
Adiponectin quartiles were negatively associated with diabetes indicators (FPG and HbA1c), obesity indicators (BMI, WC, HC and WHR), hypertension indicators ( ...
[103]
A small-molecule AdipoR agonist for type 2 diabetes and short life in ...
Nov 28, 2013 · Orally active small molecules that bind to and activate AdipoR1 and AdipoR2 could ameliorate obesity-related diseases such as type 2 diabetes.
[104]
Development of a non-invasive bioassay for adiponectin target ...
Oct 18, 2024 · This study aimed to identify peripheral biomarkers to monitor adiponectin actions using ALY688, an adiponectin receptor agonist peptide.
[105]
The fat-derived hormone adiponectin alleviates alcoholic and ... - JCI
Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant ...Missing: trials NAFLD
[106]
Effects of combined exenatide and pioglitazone therapy on hepatic ...
Combined pioglitazone and exenatide therapy was associated with a significantly greater increase in plasma adiponectin (Δ = 193%) and a significantly greater ...
[107]
Systematic Review and Meta-Analysis of Randomized ... - PubMed
Aug 13, 2019 · SGLT2 inhibitor treatment was associated with decreased circulating leptin levels and increased circulating adiponectin levels.
[108]
Adiponectin gene therapy ameliorates high-fat, high-sucrose diet ...
Sep 10, 2012 · Adiponectin gene therapy increases serum adiponectin levels in mice. To comprehensively evaluate the metabolic effects of adiponectin gene ...
[109]
Innovative gene therapy strategies for tackling obesity
Mar 31, 2025 · Studies have shown that adiponectin administration can lead to weight reduction, suggesting that adiponectin replacement therapy may be an ...
[110]
Adiponectin Does Not Cross the Blood-Brain Barrier but Modifies ...
Jan 1, 2006 · Clearance of adiponectin from blood. Half-life for clearance from blood was 43 min for nonglycosylated adiponectin and 32 min for glycosylated ...
[111]
Effect of Semaglutide Add-on to Metformin on Visceral Adiposity ...
May 20, 2025 · Adiponectin levels increased significantly post-semaglutide add-on therapy (p < 0.05). The greatest increase was observed in the obesity group ...