Adiponectin downregulates its own production and the expression of its AdipoR2 receptor in transgenic mice

Bauche, Isabelle B.; Mkadem, Samira Ait El; Rezsöhazy, René; Funahashi, Tohru; Maeda, Norikazu; Miranda, Lisa; Brichard, Sonia

doi:10.1016/j.bbrc.2006.05.033

Cited by 73 publications

(52 citation statements)

References 40 publications

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“…Similarly, AdipoR2 mRNA expression in subcutaneous fat was reduced in patients with IGT and type 2 diabetes, whereas AdipoR1 mRNA was higher in IGT and type 2 diabetic patients. It has been suggested previously that AdipoR2 may play a more substantial role in the pathogenesis of type 2 diabetes (23)(24)(25). This hypothesis is supported by the significant associations of AdipoR2 mRNA expression in adipose tissue with measures of obesity and diabetes in this study.…”

Section: Statistical Analysessupporting

confidence: 87%

Gene Expression of Adiponectin Receptors in Human Visceral and Subcutaneous Adipose Tissue Is Related to Insulin Resistance and Metabolic Parameters and Is Altered in Response to Physical Training

et al. 2007

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OBJECTIVE -Adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2, respectively) mediate the effects of adiponectin on glucose and lipid metabolism in vivo. We examined whether AdipoR1 and/or AdipoR2 mRNA expression in human adipose tissue is fat-depot specific. We also studied whether their expression in visceral and subcutaneous fat depots is associated with metabolic parameters and whether their expression is regulated by intensive physical exercise.RESEARCH DESIGN AND METHODS -We determined metabolic parameters and assessed AdipoR1 and AdipoR2 mRNA expression using quantitative real-time PCR in adipose tissue in an observational study of 153 subjects and an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes) before and after intensive physical training for 4 weeks.RESULTS -AdipoR1 and AdipoR2 mRNA expression is not significantly different between omental and subcutaneous fat, but their expression is several-fold lower in adipose tissue than in muscle. AdipoR2 mRNA expression in visceral fat is highly correlated with its expression in subcutaneous fat. AdipoR2 mRNA expression in both visceral and subcutaneous fat is positively associated with circulating adiponectin and HDL levels but negatively associated with obesity as well as parameters of insulin resistance, glycemia, and other lipid levels before and after adjustment for fat mass. Physical training for 4 weeks resulted in increased AdipoR1 and AdipoR2 mRNA expression in subcutaneous fat.CONCLUSIONS -AdipoR2 mRNA expression in fat is negatively associated with insulin resistance and metabolic parameters independently of obesity and may mediate the improvement of insulin resistance in response to exercise. Diabetes Care 30:3110-3115, 2007A diponectin is an adipose tissuesecreted cytokine that acts as a key modulator of insulin sensitivity (1,2) and glucose and lipid metabolism (3) and has pronounced antiatherosclerotic effects (4,5). The beneficial effects of this highly abundant 244 -amino acid protein hormone (circulating at ϳ10 g/ml concentration in human serum and accounting for ϳ0.01% of total plasma protein) are predominantly mediated by two cell membrane receptors, adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) (6).AdipoR1 is a high-affinity receptor for globular adiponectin, and studies in mice have shown that it is ubiquitously expressed (6 -10) but most abundantly in skeletal muscle. AdipoR2 is predominantly expressed in liver and has intermediate affinity for both full-length and globular adiponectin (6,8). Simultaneous disruption of both AdipoR1 and AdipoR2 abolished adiponectin binding and actions, resulting in increased tissue triglyceride content, inflammation, and oxidative stress, leading to insulin resistance and glucose intolerance in mice (9). Elevated expression of AdipoR1 and AdipoR2 has been associated with decreased plasma insulin levels in mice in either physiological (i.e., fasting) or pathological conditions (11). We have previously reported that prolonged e...

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Section: Statistical Analysessupporting

confidence: 87%

Gene Expression of Adiponectin Receptors in Human Visceral and Subcutaneous Adipose Tissue Is Related to Insulin Resistance and Metabolic Parameters and Is Altered in Response to Physical Training

et al. 2007

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“…Adiponectin is indeed able to downregulate its own receptors, AdipoR1 and AdipoR2. These downregulations have already been observed in different tissues and cell lines (adipose tissue, prostate cancer cell lines, and MDA-MB 231 mammary cancer cells) (Bauche et al 2006, Dos Santos et al 2008) and more particularly in human placenta (Caminos et al 2005, Mistry et al 2006. In trophoblastic cell line BeWo, we recently described that adiponectin inhibited AdipoR mRNA expression at the low concentration of 25 ng/ml (Benaitreau et al 2010).…”

Section: Discussionmentioning

confidence: 74%

Effects of adiponectin on human trophoblast invasion

Benaîtreau¹,

Santos²,

Leneveu³

et al. 2010

Journal of Endocrinology

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Adiponectin is an adipokine with insulin-sensitizing, antiinflammatory, anti-atherogenic, and anti-proliferative effects. The expression of specific adiponectin receptors in the placenta and in the endometrium suggests a role for this cytokine in placental development, but this role has not yet been elucidated. The invasion of trophoblast cells during the first trimester of pregnancy being crucial to placentation process, we have studied adiponectin effects on human trophoblast invasive capacities. We found that adiponectin stimulated human trophoblast cell migration in HTR-8/SVneo cells in a dose-independent manner. In addition, adiponectin also significantly enhanced invasion of HTR-8/SVneo cells and of human extravillous trophoblast from first trimester placenta. These pro-invasive effects of adiponectin in human trophoblasts seem to be mediated in part via increased matrix metalloproteinases (MMP2 and MMP9) activities and via repression of TIMP2 mRNA expression. Our results suggest that adiponectin could be a positive regulator of the early invasion process by modulating the MMP/TIMP balance. Moreover, these results provide an insight into the role of adiponectin in pathological conditions characterized by insufficient or excessive trophoblast invasion.

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“…67 Also, transgenic adiponectin-overexpressing mice eventually had lower circulating adiponectin level than that of wild-type mice indicating the presence of feedback regulation. 68 It is known that changes in gene expression cannot always explain the changes in circulating adiponectin levels. 69 Thus, a simple expansion of adipose tissue in healthy obese individuals should not be expected to affect the plasma level of adiponectin and the results of our analysis supported this (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Lack of association between body mass index and plasma adiponectin levels in healthy adults

Kuo

2011

Int J Obes

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Objectives: To test the hypothesis that obesity (increase in fat mass) independently affects the level of adipokines: adiponectin, tumor necrosis factor-a (TNFa) and interleukin (IL)-6. Methods: Publications in the past decade reporting adult plasma adiponectin, leptin, TNFa and/or IL-6 levels were compiled. Mean gender-specific values were extracted from studies that included medical screening to confirm physical health (43 groups, total 4852 subjects). Correlation analysis was conducted between adipokine levels and body mass index (BMI), a widely used estimate of adiposity. Results: For healthy lean to obese adults of both genders, no significant correlation between plasma adiponectin and BMI was detected. There was also no gender difference in plasma adiponectin level. In contrast, leptin levels showed a positive correlation with BMI in both genders, and women had significantly higher levels of plasma leptin consistent with a higher percentage of body fat. The proinflammatory cytokine TNFa failed to show correlation with BMI. Although IL-6 showed a positive correlation with BMI in women, the obesity-related increase was very limited. Conclusions: Data analysis based on studies performed on healthy adults did not support the hypothesis that obesity independently affects the plasma level of adiponectin and TNFa. Reported obesity-related changes in plasma adipokine levels may be a consequence of obesity-related metabolic disorders. Future studies are especially needed to understand the homeostasis of adiponectin.

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Adiponectin downregulates its own production and the expression of its AdipoR2 receptor in transgenic mice

Cited by 73 publications

References 40 publications

Gene Expression of Adiponectin Receptors in Human Visceral and Subcutaneous Adipose Tissue Is Related to Insulin Resistance and Metabolic Parameters and Is Altered in Response to Physical Training

Gene Expression of Adiponectin Receptors in Human Visceral and Subcutaneous Adipose Tissue Is Related to Insulin Resistance and Metabolic Parameters and Is Altered in Response to Physical Training

Effects of adiponectin on human trophoblast invasion

Lack of association between body mass index and plasma adiponectin levels in healthy adults

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