Regulation of Adiponectin Expression in Human Adipocytes: Effects of Adiposity, Glucocorticoids, and Tumor Necrosis Factor α

Degawa-Yamauchi, Mikako; Moss, Katherine A.; Bovenkerk, Jason E.; Shankar, Sudha; Morrison, Charles L.; Lelliott, Christopher J.; Vidal-Puig, António; Jones, Rose Marie; Considine, Robert V.

doi:10.1038/oby.2005.74

Cited by 194 publications

(146 citation statements)

References 47 publications

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“…The mechanisms underlying social-defeat-induced reduction in circulating adiponectin levels are not yet known. However, studies have shown that glucocorticoid stress hormones inhibit adiponectin gene expression and secretion both in vitro and in vivo (39)(40)(41)(42). It seems reasonable to speculate that social-defeat-induced decrease in plasma adiponectin levels may be attributed to stress-induced glucocorticoid surge.…”

Section: Discussionmentioning

confidence: 97%

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Liu¹,

Guo²,

Zhang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

154

162

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Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte-derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, "anhedonia," and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressantlike behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.

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Section: Discussionmentioning

confidence: 97%

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Liu¹,

Guo²,

Zhang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

154

162

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show abstract

“…31 Kern et al 30 found a similar negative relationship between TNFa release and adiponectin release by human adipose tissue in vitro. 30 While TNFa is a potent inhibitor of adiponectin release by murine 3T3-L1 adipocytes, 32,33 it inhibited adiponectin release by only 7% in human adipocytes. 32 However, Wang and Trayhurn 34 reported a decrease due to TNFa of adiponectin mRNA in human The values are the means of 8 experiments using fractions derived from omental adipose tissue from as many women.…”

Section: Discussionmentioning

confidence: 99%

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue

et al. 2007

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Objective: Adiponectin is an adipokine produced by adipose tissue. The present studies examined the in vitro release of adiponectin by human omental adipose tissue explants as well as the mRNA content of freshly isolated non-fat cells and adipocytes plus cultured preadipocytes and adipocytes derived from omental fat. Results: The release of adiponectin was reduced while that of interleukin-8 (IL-8) was enhanced in tissue explants from morbidly obese women. The release of adiponectin was also reduced by one-third in explants from morbidly obese diabetic women while that of IL-8 was unaffected by diabetes. The release of adiponectin was enhanced by insulin and by inhibition of endogenous tumor necrosis factor (TNFa) using etancercept. Adiponectin was released in appreciable amounts by the undigested matrix obtained by collagenase digestion of adipose tissue. The release of adiponectin by non-fat cells (matrix þ SV cells) was comparable to that by the adipocytes derived from the same amount of tissue while the adiponectin mRNA content of the pooled matrix and SV cell fractions was 40% of that in intact tissue. The adiponectin mRNA content was 48-fold greater in isolated adipocytes than in non-fat cells derived from adipose tissue. In contrast, the amount of adiponectin mRNA in vitro differentiated omental adipocytes was 1 Â l0 6 -fold greater than that in cultured preadipocytes while that of leptin was 3 Â 10 4 -fold greater. Conclusion: Adiponectin mRNA is present in the non-fat cells of freshly isolated adipose tissue and release by the non-fat cells derived from a gram of adipose tissue is comparable to that by adipocytes isolated from the same amount of tissue. While leptin is only released by mature adipocytes, adiponectin is released by both the non-fat cells and the fat cells derived from human omental adipose tissue.

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“…A c/EBP-α consensus binding site has been found in the first intron of the gene but functional significance for regulation is not yet established [32]. Glucocorticoids, TNF-α or IL-6 are putative negative regulatory factors of the adiponectin gene whereas insulin-mediated regulation has not been documented [33,34]. This may be surprising in view of the observation that insulin is able to suppress the concentra- Results are means±SD of ten subjects studied longitudinally before and during pregnancy.…”

Section: Regulation Of Adiponectin Expressionmentioning

confidence: 99%

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

et al. 2006

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Aims/hypothesis: Adiponectin is upregulated during adipogenesis and downregulated in insulin-resistant states. The mechanism(s) governing the re-arrangements from adipogenesis to facilitated lipolysis during pregnancy are unknown. Our purpose was to analyse the role of adiponectin relative to the metabolic changes in human pregnancy. Subjects, materials and methods: Lean women (BMI <25 kg/m²) were evaluated longitudinally before conception, and in early (12-14 weeks) and late (34-36 weeks) pregnancy. Insulin sensitivity was measured using the glucose clamp technique. Venous blood and subcutaneous adipose tissue biopsies were obtained at each time point. Results: Adiponectin concentrations were lower in the third trimester than in the pregravid condition (9.9±1.4 vs 13.5±1.8 μg/ml). The hypoadiponectinaemia was reflected by a 2.5-fold decrease in white adipose tissue adiponectin mRNA. These changes were associated with a 25% increase in fat mass (23.7±2.9 vs 18.9±2.9 kg). Insulin infusion decreased high molecular weight adiponectin complexes in pregravid women (9.9±0.6 vs 6.2±0.06) and the suppressive effect of insulin was lost during pregnancy. The pregnancy-mediated changes in adiponectin were strongly correlated with basal insulin levels and insulin sensitivity (p<0.0001). The relationship between adiponectin and insulin sensitivity was related to the decreased insulin regulation of glucose utilisation (r=0.55, p<0.001) but not of endogenous hepatic glucose production. Conclusions/interpretation: These data demonstrate that pregnancy is associated with adiponectin changes in lean women. Hypoadiponectinaemia is reflected by a lower amount of high molecular weight adiponectin and by the ratio of high to low molecular weight multimers. The adiponectin changes relate to decreased insulin sensitivity of glucose disposal rather than alterations of lipid metabolism.

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Regulation of Adiponectin Expression in Human Adipocytes: Effects of Adiposity, Glucocorticoids, and Tumor Necrosis Factor α

Cited by 194 publications

References 47 publications

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

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