Energy intake and adiponectin gene expression

Abstract

Hypoadiponectinemia and decreased adiponectin gene expression in white adipose tissue (WAT) have been well observed in obese subjects and animal models. However, the mechanism for obesity-associated hypoadiponectinemia is still largely unknown. To investigate the regulatory role of energy intake, dietary fat, and adiposity in adiponectin gene expression and blood adiponectin level, a series of feeding regimens was employed to manipulate energy intake and dietary fat in obese-prone C57BL/6, genetically obese ob/ob, obese-resistant A/J and peroxisome proliferator-activated receptor-␣ gene knockout (PPAR␣ KO) mice. Adiponectin gene expression in WAT and circulating adiponectin levels were studied in these dietary intervention-treated mice. Our study showed that calorie restriction (CR) robustly increased adiponectin gene expression in epididymal fat and blood adiponectin levels in both low-fat (LF) and high-fat (HF) diet-fed C57BL/6 mice. Although HF pair-fed C57BL/6 mice received the same amount of calories as LF ad libitum-fed mice, HF diet clearly increased adiposity but showed no significant effects on adiponectin gene expression and blood adiponectin level. CR also significantly increased blood adiponectin levels in ob/ob and A/J mice. Neither CR nor HF feeding displayed any significant effect on blood adiponectin half-life in C57BL/6 mice. Interestingly, CR increased PPAR␣ expression in epididymal fat of C57BL/6 mice. Low levels of blood adiponectin and adiponectin gene expression in WAT were observed in PPAR␣ KO mice. PPAR␣ agonist treatment increased adiponectin mRNA levels in 3T3-L1 adipocytes. Furthermore, CR failed to increase adiponectin gene expression and blood adiponectin levels in PPAR␣ KO mice. Therefore, our study demonstrated that energy intake, not dietary fat, plays an important role in regulating adiponectin gene expression and blood adiponectin level. PPAR␣ mediates CR-enhanced adiponectin gene expression in WAT. obesity; adipocyte; calorie restriction ADIPONECTIN IS AN ADIPOCYTE-DERIVED HORMONE with insulinsensitizing function and plays an important role in maintaining energy homeostasis. Adiponectin gene expression in white adipose tissue (WAT) and blood concentrations are inversely associated with body mass index in humans (1,8,44). However, despite the close association of adiposity and hypoadiponectinemia, it is still not certain whether WAT expansion itself reduces adiponectin gene expression and adiponectin levels in circulation.The primary function of WAT is energy storage. Prolonged positive energy imbalance or excessive energy intake increases triglyceride accumulation in adipocytes and enlarges WAT mass. Therefore, calorie-enriched foods are generally blamed as the main cause of the obesity epidemic. In addition, high-fat (HF) diet has been widely used for inducing obesity in animal models that exhibit reduced adiponectin gene expression in WAT (3,10,25). This raises the question whether energy intake or dietary fat content controls adiponectin gene expression in WAT.Calorie restri...

Overexpression of the adiponectin gene mimics the metabolic and stress resistance effects of calorie restriction, but not the anti-tumor effect

“…The present findings are in accord with those reported by Qiao et al (Qiao, 2011). Although fasting glucose levels were significantly elevated in WT-HFD compared with WT-RD mice, the insulin sensitivity assessed by Quicki did not significantly differ between the two groups.…”

“…Because many studies have reported that CR increases the plasma concentration of Adipoq in mice and rats (Berg, 2001;Zhu, 2004;Qiao, 2011), Resistance to a variety of stressors is a hallmark of CR in animals (Masoro, 1998). We assessed the survival rate after an inflammatory challenge induced by injection of a high dose of lipopolysaccharide (LPS).…”

Caloric restriction

“…Consistent with the negative relationship between fat content and circulating adiponectin levels (Rosen and Spiegelman, 2006), levels of adiponectin are increased by CR (Combs et al, 2003;Zhu et al, 2004;Wang et al, 2006), and also by IF protocols ) CR appears to be the most effective physical intervention to increases adiponectin gene expression and circulating levels in rodents (Qiao et al, 2011) thus, this elevation may mediate some of the health benefits observed with CR. Adiponectin was first identified as an adipose-tissue peptide dysregulated by obesity (Ouchi et al, 1999).…”

“…A very recent study reported that energy intake, not dietary fat or adiposity, played an important role in the regulation of gene expression and circulatory levels of adiponectin (Qiao et al, 2011). Various models, C57BL/6, genetically obese ob/ob, obese-resistant A/J and peroxisome proliferator-activated receptor-a gene knockout (PPARa KO) mice were used.…”

Anti-inflammatory Action of Calorie Restriction Underlies the Retardation of Aging and Age-Related Diseases

“…CR improves glucose, insulin levels and lipid metabolism, thereby improving quality of life via PPAR-γ expression [46]. CR also induces adiponectin gene expression through enhanced PPAR-a and suppressed PPARγ in the epididymal fat [47].…”