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. 2011 Jan 18:10:11.
doi: 10.1186/1476-511X-10-11.

High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations

Affiliations

High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations

Cristiane de Oliveira et al. Lipids Health Dis. .

Abstract

Background: Adiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. In addition, it increases fatty acid oxidation in the muscle and potentiates insulin inhibition of hepatic gluconeogenesis. Two adiponectin receptors have been identified: AdipoR1 is the major receptor expressed in skeletal muscle, whereas AdipoR2 is mainly expressed in liver. Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia; of note, all of these features are shared by the condition of insulin resistance. Although it has been shown that glucocorticoids inhibit adiponectin expression in vitro and in vivo, little is known about the regulation of adiponectin receptors. The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues.

Results: Feeding of a high-fat diet increased serum glucose levels and decreased adiponectin and adipoR2 mRNA expression in subcutaneous and retroperitoneal adipose tissues, respectively. Moreover, it increased both adipoR1 and adipoR2 mRNA levels in muscle and adipoR2 protein levels in liver. Adrenalectomy combined with the synthetic glucocorticoid dexamethasone treatment resulted in increased glucose and insulin levels, decreased serum adiponectin levels, reduced adiponectin mRNA in epididymal adipose tissue, reduction of adipoR2 mRNA by 7-fold in muscle and reduced adipoR1 and adipoR2 protein levels in muscle. Adrenalectomy alone increased adiponectin mRNA expression 3-fold in subcutaneous adipose tissue and reduced adipoR2 mRNA expression 2-fold in liver.

Conclusion: Hyperglycemia as a result of a high-fat diet is associated with an increase in the expression of the adiponectin receptors in muscle. An excess of glucocorticoids, rather than their absence, increase glucose and insulin and decrease adiponectin levels.

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Figures

Figure 1
Figure 1
Effect of a high-fat (HF) diet on adiponectin gene expression in (A) retroperitoneal (RET), (B) epididymal (EPI) and (C) subcutaneous (SUB) adipose tissue. Fold change data are expressed as the mean ± SEM. Values were normalized to HPRT gene expression with n = 5-9 per group. A Student's t-test was used for statistical comparisons between the HF and control (C) groups; *p < 0.005.
Figure 2
Figure 2
Effect of a high-fat diet (HF) on the mRNA and protein expression of the adiponectin receptors adipoR1 and adipoR2 in (A) retroperitoneal (RET), (B) epididymal (EPI) and (C) subcutaneous adipose tissue (SUB). Data are expressed as the mean ± SEM. mRNA values were normalized to HPRT, and protein values were normalized to α-tubulin with n = 5-9 per group. A Student's t-test was used for statistical comparisons between the HF and control (C) groups; *p < 0.05.
Figure 3
Figure 3
Effect of a high-fat diet (HF) on the mRNA and protein expression of the adiponectin receptors adipoR1 and adipoR2 in (A) liver and (B) muscle. Data are expressed as the mean ± SEM. Values were normalized to HPRT with n = 5-9 per group. A Student's t-test was used for statistical comparisons between the HF and control (C) groups; *p < 0.05.
Figure 4
Figure 4
Effects of adrenalectomy (ADREC) and adrenalectomy with dexamethasone treatment (A-DEXA; 0.2 mg/100 g, twice per day) on adiponectin gene expression in (A) retroperitoneal (RET), (B) epididymal (EPI) and (C) subcutaneous (SUB) adipose tissue in rats treated with HF diet. Data are expressed as the mean ± SEM. Values were normalized to HPRT levels with n = 5-9 per group. A one-way ANOVA followed by a Tukey post-hoc test was used to determine significant differences between groups (*p < 0.05, effect due to surgery). S-ADREC, sham adrenalectomy.
Figure 5
Figure 5
Effects of adrenalectomy (ADREC) and adrenalectomy with dexamethasone treatment (A-DEXA; 0.2 mg/100 g, twice per day) on the gene and protein expression of the adiponectin receptors adipoR1 and adipoR2 in (A) retroperitoneal (RET), (B) epididymal (EPI) and (C) subcutaneous (SUB) adipose tissue in rats treated with high-fat (HF) diet. Data are expressed as the mean ± SEM. mRNA values were normalized to HPRT, and protein values were normalized to α-tubulin with n = 5-9 per group. A one-way ANOVA followed by a Tukey post-hoc test was used to determine significant differences between groups (*p < 0.05, **p < 0.01, effect due to surgery). S-ADREC, sham adrenalectomy.
Figure 6
Figure 6
Effects of adrenalectomy (ADREC) and adrenalectomy with dexamethasone treatment (A-DEXA; 0.2 mg/100 g, twice per day) on gene expression of the adiponectin receptors adipoR1 and adipoR2 gene in (A) muscle and (B) liver. Data are expressed as the mean ± SEM. Values were normalized to HPRT with n = 5-9 per group. A one-way ANOVA followed by a Tukey post-hoc test was used to determine significant differences between groups (*p < 0.05, **p < 0.01, ***p < 0.005, effect due to surgery). S-ADREC, sham adrenalectomy.

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