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Nature Communications Oct 2023Adiponectin is a secretory protein, primarily produced in adipocytes. However, low but detectable expression of adiponectin can be observed in cell types beyond...
Adiponectin is a secretory protein, primarily produced in adipocytes. However, low but detectable expression of adiponectin can be observed in cell types beyond adipocytes, particularly in kidney tubular cells, but its local renal role is unknown. We assessed the impact of renal adiponectin by utilizing male inducible kidney tubular cell-specific adiponectin overexpression or knockout mice. Kidney-specific adiponectin overexpression induces a doubling of phosphoenolpyruvate carboxylase expression and enhanced pyruvate-mediated glucose production, tricarboxylic acid cycle intermediates and an upregulation of fatty acid oxidation (FAO). Inhibition of FAO reduces the adiponectin-induced enhancement of glucose production, highlighting the role of FAO in the induction of renal gluconeogenesis. In contrast, mice lacking adiponectin in the kidney exhibit enhanced glucose tolerance, lower utilization and greater accumulation of lipid species. Hence, renal adiponectin is an inducer of gluconeogenesis by driving enhanced local FAO and further underlines the important systemic contribution of renal gluconeogenesis.
Topics: Animals; Male; Mice; Adiponectin; Gluconeogenesis; Glucose; Kidney; Liver; Mice, Knockout; Pyruvic Acid
PubMed: 37848446
DOI: 10.1038/s41467-023-42188-4 -
Biochimie Oct 2012Adiponectin has been receiving a great deal of attention due to its potential therapeutic use for metabolic and cardiovascular disorders. Adiponectin expression levels... (Review)
Review
Adiponectin has been receiving a great deal of attention due to its potential therapeutic use for metabolic and cardiovascular disorders. Adiponectin expression levels and multimerization are down-regulated in obesity and up-regulated by insulin sensitizers such as thiazolidinediones (TZDs), metformin, sulfonylurea and resveratrol (RSV). The precise mechanisms underlying adiponectin up- and down-regulation remain largely unknown, but recent studies indicate that the cellular and plasma levels of adiponectin could be regulated at both transcriptional and post-transcriptional levels. At the post-translational level, TZDs and resveratrol promote adiponectin levels and multimerization via up-regulation of disulfide-bond-A oxidoreductase-like protein (DsbA-L). Adiponectin levels are also stimulated by FOXO1 and AMP-activated protein kinase (AMPK), and are suppressed by PKA or silencing mediator of retinoid and thyroid hormone receptors (SMRT). Since multimerization is important not only for adiponectin function but also for stability, increasing adiponectin multimerization has become a promising drug target for the treatment of metabolic diseases and other related disorders.
Topics: Adiponectin; Animals; Down-Regulation; Humans; PPAR gamma; Protein Multimerization; Small Molecule Libraries; Up-Regulation
PubMed: 22342903
DOI: 10.1016/j.biochi.2012.01.008 -
Nutricion Hospitalaria Jun 2016Adiponectin, an adipocyte derived peptide, has anti-inflammatory and antiatherogenic effects, and improves insulin sensitivity. However, little is known about dietary...
INTRODUCTION
Adiponectin, an adipocyte derived peptide, has anti-inflammatory and antiatherogenic effects, and improves insulin sensitivity. However, little is known about dietary predictors and their interactions with lifestyle on adiponectin concentrations, in apparently healthy young adults.
OBJECTIVE
To evaluate the associations between plasma concentrations of adiponectin with dietary components and lifestyle in apparently healthy young adults.
METHODS
Anthropometric and body composition, systolic and diastolic blood pressure, diet and lifestyle data of 157 healthy young adults, aged 18 and 35, were collected and analyzed. Blood samples were collected after fasting for 12 hours to determine adiponectin concentrations. Dietary and anthropometric indexes were calculated and analyzed.
RESULTS
Adiponectin concentrations were significantly higher for women compared to men; and there was an indirect and significant correlation between adiponectin concentrations with BMI. There was a significant association between adiponectin concentrations with the healthy eating index, calories, lipids, proteins, fibers, riboflavin, and phosphorus, among others; and a tendency with carbohydrates and niacin. In multiple linear regression analysis, fiber and riboflavin (r2 = 0.0928; p = 0.0013) and carbohydrates and phosphorus were associated with the concentrations of adiponectin. The association with carbohydrates and phosphorus suffered interaction with gender (r2 = 0.2400; p < 0.0001), as well as the association with phosphorus also suffered interaction with physical activity (r2 = 0.1275; p = 0.0003).
CONCLUSION
Plasma concentrations of adiponectin, in healthy young adults, seem to be modulated by components of diet depending on gender and physical activity.
Topics: Adiponectin; Adolescent; Adult; Body Composition; Feeding Behavior; Female; Humans; Life Style; Male; Sex Characteristics; Young Adult
PubMed: 27513491
DOI: 10.20960/nh.264 -
The Journal of Endocrinology Aug 2022Adiponectin is a cytokine secreted from adipocytes and regulates metabolism. Although serum adiponectin levels show diurnal variations, it is not clear if the effects of...
Adiponectin is a cytokine secreted from adipocytes and regulates metabolism. Although serum adiponectin levels show diurnal variations, it is not clear if the effects of adiponectin are time-dependent. Therefore, this study conducted locomotor activity analyses and various metabolic studies using the adiponectin knockout (APN (-/-)) and the APN (+/+) mice to understand whether adiponectin regulates the circadian rhythm of glucose and lipid metabolism. We observed that the adiponectin gene deficiency does not affect the rhythmicity of core circadian clock genes expression in several peripheral tissues. In contrast, the adiponectin gene deficiency alters the circadian rhythms of liver and serum lipid levels and results in the loss of the time dependency of very-low-density lipoprotein-triglyceride secretion from the liver. In addition, the whole-body glucose tolerance of the APN (-/-) mice was normal at CT10 but reduced at CT22, compared to the APN (+/+) mice. The decreased glucose tolerance at CT22 was associated with insulin hyposecretion in vivo. In contrast, the gluconeogenesis activity was higher in the APN (-/-) mice than in the APN (+/+) mice throughout the day. These results indicate that adiponectin regulates part of the circadian rhythm of metabolism in the liver.
Topics: Adiponectin; Animals; Circadian Clocks; Circadian Rhythm; Glucose; Lipid Metabolism; Liver; Metabolism, Inborn Errors; Mice
PubMed: 35662074
DOI: 10.1530/JOE-22-0006 -
Best Practice & Research. Clinical... Jan 2014Adiponectin, which exists in serum in three major complexes including trimer, hexamer, and the high molecular weight (HMW) form, has strong insulin sensitizing,... (Review)
Review
Adiponectin, which exists in serum in three major complexes including trimer, hexamer, and the high molecular weight (HMW) form, has strong insulin sensitizing, anti-inflammatory and anti-diabetic functions. Different adiponectin complexes exert tissue-specific biological functions and activate distinct signaling pathways. In this review, we summarize our current understanding on the mechanisms regulating adiponectin multimerization. We also describe the major target tissues in which distinct adiponectin multimers exert their functional roles. Finally, we discuss the potential involvement of endoplasmic reticulum stress and mitochondrial stress in diet-induced adiponectin downregulation and highlight the roles of Disulfide bond A oxidoreductase-like protein (DsbA-L) in the prevention of endoplasmic reticulum stress and promotion of adiponectin multimerization, stability, and function.
Topics: AMP-Activated Protein Kinases; Adiponectin; Animals; Central Nervous System; Endoplasmic Reticulum Stress; Glutathione Transferase; Humans; Liver; Mice; Muscle, Skeletal; Protein Multimerization; Protein Stability; Signal Transduction
PubMed: 24417943
DOI: 10.1016/j.beem.2013.06.003 -
Revista Da Associacao Medica Brasileira... 2015the conditions of obesity and overweight pose a major risk for a number of comorbidities, including clinical syndromes resulting from atherosclerotic disease. Recent... (Review)
Review
OBJECTIVES
the conditions of obesity and overweight pose a major risk for a number of comorbidities, including clinical syndromes resulting from atherosclerotic disease. Recent studies strongly indicate that adipose tissue is an active endocrine organ that secretes bioactive factors such as adipokines. Adiponectin appears to have a regulatory role in the mechanism of insulin resistance and in the development of atherosclerosis. This systematic review aims to evaluate the anti-atherogenic effects of adiponectin and its properties to improve and mimic metabolic and vascular actions of insulin and its influence on endothelial function.
METHODS
a qualitative, exploratory and literature review was performed in the PubMed, Portal Capes and Scielo databases using as key-words "adiponectin", "obesity", "insulin resistance", "anti-inflammatory", "therapeutic strategies" and "future prospects".
RESULTS
evidence suggests that adiponectin has anti-atherogenic properties with anti-inflammatory effects on the vascular wall. Moreover, it modifies the vascular intracellular signaling and has indirect antioxidant effects on the human myocardium. On the other hand, there are studies suggesting that increased levels of adiponectin are paradoxically associated with a worse prognosis in heart failure syndrome, although the mechanisms are not clear.
CONCLUSION
it is not clear whether adiponectin levels have any clinical significance for risk stratification in cardiovascular disease or if they simply reflect the activation of complex underlying mechanisms. Changes in lifestyle and some drug treatments for hypertension and coronary heart disease have shown significant effect to increase adiponectin levels, and simultaneously decrease in insulin resistance and endothelial dysfunction.
Topics: Adiponectin; Adipose Tissue; Cardiovascular Diseases; Female; Humans; Insulin Resistance; Life Style; Male; Obesity; Receptors, Adiponectin; Risk Factors
PubMed: 25909213
DOI: 10.1590/1806-9282.61.01.072 -
The Journal of Clinical Investigation Jul 2006Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by... (Review)
Review
Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic metabolic actions of adiponectin, have been cloned and are downregulated in obesity-linked insulin resistance. Upregulation of adiponectin is a partial cause of the insulin-sensitizing and antidiabetic actions of thiazolidinediones. Therefore, adiponectin and adiponectin receptors represent potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance. This Review describes the pathophysiology of adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.
Topics: Adiponectin; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Metabolic Syndrome; Polymorphism, Single Nucleotide; Receptors, Adiponectin; Receptors, Cell Surface
PubMed: 16823476
DOI: 10.1172/JCI29126 -
Best Practice & Research. Clinical... Jan 2014Obesity is linked to increased cancer risk. Pathological expansion of adipose tissue impacts adipocyte function and secretion of hormonal factors regulating tissue... (Review)
Review
Obesity is linked to increased cancer risk. Pathological expansion of adipose tissue impacts adipocyte function and secretion of hormonal factors regulating tissue homeostasis and metabolism. Adiponectin is an adipocyte-secreted, circulating hormone with pleiotropic functions in lipid and glucose metabolism, and beneficial roles in cardiovascular functions and inflammation. In obesity, decreased Adiponectin plasma levels correlate with tumor development and progression. The association of Adiponectin with potential tumor-limiting functions has raised significant interest in exploring this adipokine as a target for cancer-diagnostic and therapeutic applications. Recent studies, however, also implicate Adiponectin in supporting malignancy. This review highlights the evidence that links Adiponectin signaling to either cancer-protective or cancer-supporting functions. In this context, we discuss Adiponectin interactions with its receptors and associated signaling pathways. Despite significant advances in understanding Adiponectin functions and signaling mechanisms, its role in cancer remains multifaceted and subject to controversy.
Topics: AMP-Activated Protein Kinases; Adiponectin; Adipose Tissue; Biomarkers, Tumor; Cadherins; Carcinogens; Enzyme Activation; Humans; Insulin; Neoplasms; Neovascularization, Pathologic; Receptors, Adiponectin; Signal Transduction; Tumor Suppressor Proteins; Wnt Signaling Pathway
PubMed: 24417946
DOI: 10.1016/j.beem.2013.11.005 -
Trends in Cardiovascular Medicine Nov 2014Adiponectin exerts both vasodilatory and insulin-sensitizing actions and its levels are decreased in insulin-resistant humans and animals. The mechanisms underlying... (Review)
Review
Adiponectin exerts both vasodilatory and insulin-sensitizing actions and its levels are decreased in insulin-resistant humans and animals. The mechanisms underlying adiponectin׳s insulin-sensitizing effect have been extensively investigated but remain largely unclear. Muscle microvasculature critically regulates muscle insulin action by modulating insulin delivery to the microvessels nurturing the muscle cells and the trans-endothelial insulin transport. We have recently reported that adiponectin exerts its insulin-sensitizing effect via recruiting muscle microvasculature, expanding the endothelial surface area, and increasing insulin delivery to and thus action in muscle. The current review focuses on the microvascular connection between the adiponectin and insulin cross talk.
Topics: Adiponectin; Blood Vessels; Humans; Insulin; Insulin Resistance; Receptor Cross-Talk
PubMed: 25220977
DOI: 10.1016/j.tcm.2014.08.001 -
Critical Care (London, England) Apr 2011Adiponectin is an adipokine first described just over a decade ago. Produced almost exclusively by adipocytes, adiponectin circulates in high concentrations in human... (Review)
Review
Adiponectin is an adipokine first described just over a decade ago. Produced almost exclusively by adipocytes, adiponectin circulates in high concentrations in human plasma. Research into this hormone has revealed it to have insulin-sensitizing, anti-inflammatory and cardioprotective roles. This review discusses the history, biology and physiological role of adiponectin and explores its role in disease, with specific focus on adiponectin in inflammation and sepsis. It appears that an inverse relationship exists between adiponectin and inflammatory cytokines. Low levels of adiponectin have been found in critically ill patients, although data are limited in human subjects at this stage. The role of adiponectin in systemic inflammation and critical illness is not well defined. Early data suggest that plasma levels of adiponectin are decreased in critical illness. Whether this is a result of the disease process itself or whether patients with lower levels of this hormone are more susceptible to developing a critical illness is not known. This observation of lower adiponectin levels then raises the possibility of therapeutic options to increase circulating adiponectin levels. The various options for modulation of serum adiponectin (recombinant adiponectin, thiazolidinediones) are discussed.
Topics: Adipocytes; Adiponectin; Amino Acid Sequence; Animals; Biomarkers; Critical Illness; Drug Delivery Systems; Humans; Inflammation Mediators; Molecular Sequence Data
PubMed: 21586104
DOI: 10.1186/cc10021