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Adiponectin
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Shinji Kihara – One of the best experts on this subject based on the ideXlab platform.
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effect of Adiponectin on murine colitis induced by dextran sulfate sodium
Gastroenterology, 2006Co-Authors: Tamao Nishihara, Kazuya Oshima, Morihiro Matsuda, Shinji Kihara, Tohru Funahashi, Hiroshi Araki, Iichiro ShimomuraAbstract:Background & Aims: Adiponectin, an adipose tissue–derived hormone, exhibits anti-inflammatory properties and has various biological functions, such as increasing insulin sensitivity, reducing hypertension, and suppressing atherosclerosis, liver fibrfibrosis, and tumor growth. The aim of the present study was to determine the effect of Adiponectin on intestinal inflammation. Methods: We investigated the effect of Adiponectin on dextran sulfate sodium (DSS)-induced colitis by using Adiponectin-knockout (APN-KO) mice and an adenovirus-mediated Adiponectin expression system. We also examined the contribution of Adiponectin deficiency to trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the effect of Adiponectin on intestinal epithelial cells. Results: After administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe colitis compared with wild-type mice. The messenger RNA expression levels of chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO mice compared with wild-type mice, accompanied by increased cellular infiinfiltration, including macrophages. Adenovirus-mediated supplementation of Adiponectin significantly attenuated the severity of colitis, but there were no differences in the severity of TNBS-induced colitis between the 2 groups. Adiponectin receptors were expressed in intestinal epithelial cells, and Adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in intestinal epithelial cells. Conclusions: Adiponectin is protective against DSS-induced murine colitis, probably due to the inhibition of chemokine production in intestinal epithelial cells and the following inflammatory responses, including infiltration of macrophages and release of proinflammatory cytokines.
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Adiponectin protects against myocardial ischemia reperfusion injury through ampk and cox 2 dependent mechanisms
Nature Medicine, 2005Co-Authors: Rei Shibata, Shinji Kihara, Kaori Sato, David R Pimentel, Yukihiro Takemura, Koji Ohashi, Tohru Funahashi, Noriyuki Ouchi, Kenneth WalshAbstract:Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infainfarction. Here, we examine the role of Adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in Adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrnecrosis factor (TNF)-α expression compared with wild-type mice. Administration of Adiponectin diminished infarct size, apoptosis and TNF-α production in both APN-KO and wild-type mice. In cultured cardiac cells, Adiponectin inhibited apoptosis and TNF-α production. Dominant negative AMP-activated protproteinase (AMPK) reversed the inhibitory effects of Adiponectin on apoptosis but had no effect on the suppressive effect of Adiponectin on TNF-α production. Adiponectin induced cyclooxygenase (COX)-2–dependent synthesis of prostaglandin E2 in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of Adiponectin on TNF-α production and infarct size. These data suggest that Adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2–dependent mechanisms.
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selective suppression of endothelial cell apoptosis by the high molecular weight form of Adiponectin
Circulation Research, 2004Co-Authors: Hideki Kobayashi, Shinji Kihara, Masahiro Kumada, Kenneth Walsh, Tohru Funahashi, Noriyuki Ouchi, Yuki Abe, Yuji MatsuzawaAbstract:Adiponectin is an adipocyte-derived, antiatherogenic protein that is present in serum as three isoforms. Total Adiponectin levels are decreased in obese or diabetic humans or animal models. This study was designed to elucidate the relative isoform distribution of Adiponectin in human disease states and identify the active form of Adiponectin toward vascular endothelial cells. The percentage of high molecular weight form (HMW) per total Adiponectin was significantly lower in patients with coronary arteartery disease than control subjects, whereas the hexamer form was similar and the trimer form was significantly higher. During weight reduction in obese subjects, the HMW form increased and the trimer and hexamer forms decreased. Recombinant Adiponectin dose-dependently suppressed apoptosis and caspase-3 activity in human umbilical vein endothelial cells (HUVECs). Transduction with dominant-negative AMP-activated protproteinase (AMPK) abolished the suppressive effect of Adiponectin on HUVECs. Gel filtfiltration chromatography was used to separate the Adiponectin isoforms, and the antiapoptotic effect toward HUVECs was only observed with the HMW form. These data suggest that HMW Adiponectin specifically confers the vascular-protective activities of this adipocytokine. The full text of this article is available online at http://circres.ahajournals.org.
Changhua Wang – One of the best experts on this subject based on the ideXlab platform.
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Heat shock protein 60 (HSP60) modulates Adiponectin signaling by stabilizing Adiponectin receptor.
Cell communication and signaling : CCS, 2020Co-Authors: Deling Zhang, Hua Liu, Yemin Zhang, Yuyang Zheng, Zhongyuan Wen, Changhua WangAbstract:Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with Adiponectin receptors. Its abundance was positively associated with Adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of Adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of Adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with Adiponectin receptors and mediated Adiponectin signaling through stabilizing Adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which Adiponectin exerts its action. Video abstract.
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Heat shock protein 60 (HSP60) modulates Adiponectin signaling by stabilizing Adiponectin receptor
, 2020Co-Authors: Deling Zhang, Hua Liu, Yemin Zhang, Yuyang Zheng, Zhongyuan Wen, Changhua WangAbstract:Abstract Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with Adiponectin receptors. Its abundance was positively associated with Adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of Adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of Adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with Adiponectin receptors and mediated Adiponectin signaling through stabilizing Adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which Adiponectin exerts its action.
Christos S Mantzoros – One of the best experts on this subject based on the ideXlab platform.
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the role of Adiponectin in cancer a review of current evidence
Endocrine Reviews, 2012Co-Authors: Maria Dalamaga, Kalliope N Diakopoulos, Christos S MantzorosAbstract:Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD)butalsowithvarioustypesofmalignancies.Adiponectin,themostabundantproteinsecretedbyadipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties.CirculatingAdiponectinlevels,whicharedeterminedpredominantlybygeneticfactors,diet,physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, Adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express Adiponectin receptors, and Adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of Adiponectin. Studies in both animals and humans have investigated Adiponectin and Adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of Adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either Adiponectin per se or medications that increase Adiponectin levels or up-regulate signaling pathways downstream of Adiponectin may prove to be useful anticancer agents. This review presents the role of Adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between Adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies. (Endocrine Reviews 33: 547–594, 2012)
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Adiponectin in insulin resistance lessons from translational research
The American Journal of Clinical Nutrition, 2010Co-Authors: Florencia Ziemke, Christos S MantzorosAbstract:Adiponectin is an adipose tissue-secreted endogenous insulin sensitizer, which plays a key role as a mediator of peroxisome proliferator-activated receptor gamma action. Adiponectin alters glucose metabolism and insulin sensitivity, exhibits antiinflammatory and antiatherogenic properties, and has been linked to several malignancies. Circulating concentrations of Adiponectin are determined primarily by genetic factors, nutrition, exercise, and abdominal adiposity. Adiponectin concentrations are lower in subjects with obesity, metabolic syndrome, and cardiovascular disease. Adiponectin knockout mice manifest glucose intolerance, insulin resistance, and hyperlipidemia and tend to develop malignancies especially when on high-fat diets. Animal studies have also shown beneficial effects of Adiponectin in rodents in vivo. Circulating concentrations of Adiponectin are lower in patients with diabetes, cardiovascular disease, and several malignancies. Studies to date provide promising results for the diagnostic and therapeutic role of Adiponectin in obesity, insulin resistance, diabetes, cardiovascular disease, and obesity-associated malignancies.
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serum Adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans cross sectional and interventional studies
The Journal of Clinical Endocrinology and Metabolism, 2003Co-Authors: Alina Gavrila, Jean L Chan, Nikos Yiannakouris, Meropi D Kontogianni, Lisa C Miller, Christine Orlova, Christos S MantzorosAbstract:Adiponectin is an adipocyte-secreted protein that circulates in high concentrations in the serum and acts to increase insulin sensitivity. Previous studies have shown that serum Adiponectin is inversely associated with fat mass and insulin resistance in humans and that acute fasting decreases adipose tissue Adiponectin mRNA expression in rodents. Whether acute energy deprdeprivation, body fat distribution, or serum hormone levels are associated with circulating Adiponectin in humans remains largely unknown. To identify predictors of serum Adiponectin levels, we evaluated the association of Adiponectin with several anthropometric, metabolic, and hormonal variables in a cross-sectional study of 121 women without a known history of diabetes. We also performed interventional studies to assess whether fasting for 48 h and/or leptin administration regulates serum Adiponectin in healthy men and women. Our cross-sectional study shows that, in addition to overall obesity, central fat distribution is an independent negative predictor of serum Adiponectin and suggests that Adiponectin may represent a link between central obesity and insulin resistance. In addition, estradiol is negatively and independently associated with Adiponectin, whereas there is no association between serum Adiponectin and leptin, cortisol, or free testosterone levels. Our interventional studies demonstrate that neither fasting for 48 h, resulting in a low leptin state, nor leptin administration at physiological or pharmacological doses alters serum Adiponectin levels. Further studies are needed to fully elucidate the physiology of Adiponectin in humans and its role in the pathogenesis of insulin-resistant states.
Iichiro Shimomura – One of the best experts on this subject based on the ideXlab platform.
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Pathophysiological significance of Adiponectin.
Medical molecular morphology, 2007Co-Authors: Makoto Nishida, Tohru Funahashi, Iichiro ShimomuraAbstract:Adipose tissue, which classically has been considered as an energy-storing organ, is now viewed as a massive source of bioactive substances such as leptin, tumor necrnecrosis factor (TNF)-α, and Adiponectin. Adiponectin was discovered to be the most abundant adipose-specific transcript. Its function had been unclear, but epidemiological and clinical studies have demonstrated that serum levels of Adiponectin are inversely associated with body weight, especially abdominal visceral fat accumulation. In addition, Adiponectin was inversely related to cardiovascular risk factors, such as insulin resistance, blood pressure, and low-density lipoprotein (LDL) cholesterol and triglyceride levels, and was positively related to high-density lipolipoprotein (HDL) cholesterol levels. Moreover, low Adiponectin concentration is associated with a high incidence of cardiovascular disease (CVD), diabetes, some kinds of cancer, and other various diseases. These associations suggest the clinical significance of Adiponectin, and a number of investigations are now being conducted to clarify the biological functions of Adiponectin. Recent studies have revealed that Adiponectin exhibits antiinflammatory, antiatherogenic, and antidiabetic properties. In addition, Adiponectin has been thought to be a key molecule in “metabolic syndrome,” which is an epidemiological target for preventing cardiovascular disease. Various functions of Adiponectin may possibly serve to prevent and treat obesity-related diseases and CVD. Furthermore, enhancement of Adiponectin secretion or action may become a promising therapeutic target.
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effect of Adiponectin on murine colitis induced by dextran sulfate sodium
Gastroenterology, 2006Co-Authors: Tamao Nishihara, Kazuya Oshima, Morihiro Matsuda, Shinji Kihara, Tohru Funahashi, Hiroshi Araki, Iichiro ShimomuraAbstract:Background & Aims: Adiponectin, an adipose tissue–derived hormone, exhibits anti-inflammatory properties and has various biological functions, such as increasing insulin sensitivity, reducing hypertension, and suppressing atherosclerosis, liver fibrosis, and tumor growth. The aim of the present study was to determine the effect of Adiponectin on intestinal inflammation. Methods: We investigated the effect of Adiponectin on dextran sulfate sodium (DSS)-induced colitis by using Adiponectin-knockout (APN-KO) mice and an adenovirus-mediated Adiponectin expression system. We also examined the contribution of Adiponectin deficiency to trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the effect of Adiponectin on intestinal epithelial cells. Results: After administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe colitis compared with wild-type mice. The messenger RNA expression levels of chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO mice compared with wild-type mice, accompanied by increased cellular infiltration, including macrophages. Adenovirus-mediated supplementation of Adiponectin significantly attenuated the severity of colitis, but there were no differences in the severity of TNBS-induced colitis between the 2 groups. Adiponectin receptors were expressed in intestinal epithelial cells, and Adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in intestinal epithelial cells. Conclusions: Adiponectin is protective against DSS-induced murine colitis, probably due to the inhibition of chemokine production in intestinal epithelial cells and the following inflammatory responses, including infiltration of macrophages and release of proinflammatory cytokines.
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Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast
Biochemical and Biophysical Research Communications, 2005Co-Authors: Kazuya Oshima, Iichiro Shimomura, Akihide Nampei, Morihiro Matsuda, Masanori Iwaki, Atsunori Fukuhara, Jun Hashimoto, Hideki YoshikawaAbstract:Adiponectin, an adipose-derived hormone, exhibits various biological functions, such as increasing insulin sensitivity, protecting hypertension, and suppression of atherosclerosis, liver fibrfibrosis, and tumor growth. Here, we report the role of Adiponectin on bone metabolism. C57BL/6J mice were treated with adenovirus expressing lacZ or Adiponectin, and their bones were analyzed by three-dimensional microcomputed tomography. Adiponectin–adenovirus treatment increased trabecular bonebone mass, accompanied by decreased number of osteoclasts and levels of plasma NTx, a bone-resorption marker. In vitro studies showed that Adiponectin inhibited M-CSF- and RANKL-induced differentiation of mouse bone marrow macrophages and human CD14-positive mononuclear cells into osteoclasts and also suppressed the bone-resorption activity of osteoclasts. Furthermore, Adiponectin enhanced mRNA expression of alkaline phosphosphatase and mineralization activity of MC3T3-E1 osteoblasts. Our results indicate that Adiponectin exerts an activity to increase bone mass by suppressing osteoclastogenesis and by activating osteoblastogenesis, suggesting that Adiponectin manipulation could be therapeutically beneficial for patients with osteopenia.
Tohru Funahashi – One of the best experts on this subject based on the ideXlab platform.
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Adiponectin, change in Adiponectin, and progression to diabetes in the diabetes prevention program
Diabetes, 2008Co-Authors: Kieren J. Mather, Tohru Funahashi, Yuji Matsuzawa, Sharon L. Edelstein, George A. Bray, Steven E. Kahn, Jill P. Crandall, Santica M. Marcovina, Barry J. Goldstein, Ronald N. GoldbergAbstract:OBJECTIVE— To determine whether baseline Adiponectin levels or intervention-associated change in Adiponectin levels were independently associated with progression to diabetes in the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS— Cox proportional hazards analysis was used to evaluate the contribution of Adiponectin and treatment-related change in Adiponectin to risk of progression to diabetes. RESULTS— Baseline Adiponectin was a strong independent predictor of incident diabetes in all treatment groups (hazard ratio per ∼3 μg/ml higher level; 0.61 in the lifestyle, 0.76 in the metformin, and the 0.79 in placebo groups; all P P = 0.13 comparing groups). Baseline differences in Adiponectin between sexes and race/ethnicity groups were not reflected in differences in diabetes risk. DPP interventions increased Adiponectin levels ([means ± SE] 0.83 ± 0.05 μg/ml in the lifestyle group, 0.23 ± 0.05 μg/ml in the metformin group, and 0.10 ± 0.05 μg/ml in the placebo group; P P P P = 0.18), and 0.89 in the placebo group; P = 0.02 per ∼1 μg/ml increase, P = 0.02 comparing groups). In the lifestyle group, adjusting for change in weight reduced, but did not remove, the effect of increased Adiponectin. CONCLUSIONS— Adiponectin is a powerful marker of diabetes risk in subjects at high risk for diabetes, even after adjustment for weight. An increase in Adiponectin in the lifestyle and placebo groups was associated with a reduction in diabetes risk. However, these changes in Adiponectin were comparatively small and less strongly related to diabetes outcome than baseline Adiponectin levels.
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Pathophysiological significance of Adiponectin.
Medical molecular morphology, 2007Co-Authors: Makoto Nishida, Tohru Funahashi, Iichiro ShimomuraAbstract:Adipose tissue, which classically has been considered as an energy-storing organ, is now viewed as a massive source of bioactive substances such as leptin, tumor necrosis factor (TNF)-α, and Adiponectin. Adiponectin was discovered to be the most abundant adipose-specific transcript. Its function had been unclear, but epidemiological and clinical studies have demonstrated that serum levels of Adiponectin are inversely associated with body weight, especially abdominal visceral fat accumulation. In addition, Adiponectin was inversely related to cardiovascular risk factors, such as insulin resistance, blood pressure, and low-density lipoprotein (LDL) cholesterol and triglyceride levels, and was positively related to high-density lipoprotein (HDL) cholesterol levels. Moreover, low Adiponectin concentration is associated with a high incidence of cardiovascular disease (CVD), diabetes, some kinds of cancer, and other various diseases. These associations suggest the clinical significance of Adiponectin, and a number of investigations are now being conducted to clarify the biological functions of Adiponectin. Recent studies have revealed that Adiponectin exhibits antiinflammatory, antiatherogenic, and antidiabetic properties. In addition, Adiponectin has been thought to be a key molecule in “metabolic syndrome,” which is an epidemiological target for preventing cardiovascular disease. Various functions of Adiponectin may possibly serve to prevent and treat obesity-related diseases and CVD. Furthermore, enhancement of Adiponectin secretion or action may become a promising therapeutic target.
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effect of Adiponectin on murine colitis induced by dextran sulfate sodium
Gastroenterology, 2006Co-Authors: Tamao Nishihara, Kazuya Oshima, Morihiro Matsuda, Shinji Kihara, Tohru Funahashi, Hiroshi Araki, Iichiro ShimomuraAbstract:Background & Aims: Adiponectin, an adipose tissue–derived hormone, exhibits anti-inflammatory properties and has various biological functions, such as increasing insulin sensitivity, reducing hypertension, and suppressing atherosclerosis, liver fibrosis, and tumor growth. The aim of the present study was to determine the effect of Adiponectin on intestinal inflammation. Methods: We investigated the effect of Adiponectin on dextran sulfate sodium (DSS)-induced colitis by using Adiponectin-knockout (APN-KO) mice and an adenovirus-mediated Adiponectin expression system. We also examined the contribution of Adiponectin deficiency to trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the effect of Adiponectin on intestinal epithelial cells. Results: After administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe colitis compared with wild-type mice. The messenger RNA expression levels of chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO mice compared with wild-type mice, accompanied by increased cellular infiltration, including macrophages. Adenovirus-mediated supplementation of Adiponectin significantly attenuated the severity of colitis, but there were no differences in the severity of TNBS-induced colitis between the 2 groups. Adiponectin receptors were expressed in intestinal epithelial cells, and Adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in intestinal epithelial cells. Conclusions: Adiponectin is protective against DSS-induced murine colitis, probably due to the inhibition of chemokine production in intestinal epithelial cells and the following inflammatory responses, including infiltration of macrophages and release of proinflammatory cytokines.