A High‐Fat Diet Has a Tissue‐Specific Effect on Adiponectin and Related Enzyme Expression

Abstract

BARNEA, MAAYAN, AVI SHAMAY, ALIZA H. STARK, AND ZECHARIA MADAR. A high-fat diet has a tissue-specific effect on adiponectin and related enzyme expression. Obesity. 2006;14:2145-2153. Objective: This study was designed to test whether adiponectin plays a role in diet-induced obesity and insulin resistance and acts as a mediator to induce or inhibit specific metabolic pathways involved in lipid metabolism Research Methods and Procedures: Forty C57BL/6J male mice were fed either a high-fat (HF) or control diet for 4 months, and adiponectin, its receptors, and enzyme expression in liver and muscle tissue were measured. Results: Mice fed the HF diet exhibited significantly greater weight gain, abnormal oral glucose tolerance test curves, and elevated homeostasis model assessment of insulin resistance (5.3 Ϯ 0.89 vs. 2.8 Ϯ 0.39). A significant reduction of adiponectin RNA expression (51%) and protein levels (15%) was observed in the adipose tissue of HF animals; however, serum adiponectin levels did not differ between groups (7.12 Ϯ 0.34 g/mL vs. 6.44 Ϯ 0.38 g/mL). Expression of hepatic mRNA of AdipoR1 and AdipoR2 was reduced by 15% and 25%, respectively, in animals fed the HF diet. In contrast, receptor mRNA expression of AdipoR1 and AdipoR2 increased by 25% and 30%, respectively, in muscle tissue. No effect was found on hepatic adenosine monophosphate-activated protein kinase expression; however, a significant reduction of phosphoadenosine monophosphate kinase levels in muscles was observed. Hepatic acetyl-coenzyme A carboxylase was similar between groups, but in muscles, the inactive form phosphoacetylcoenzyme A carboxylase was significantly reduced (p Ͻ 0.05). Discussion: The HF diet led to decreased insulin sensitivity accompanied by impaired activity of adiponectin-related enzymes in skeletal muscles but not in the liver. These results suggest that the HF diet has a tissue-specific effect on adiponectin and associated enzyme expression.

Infusion of a Lipid Emulsion Modulates AMPK and Related Proteins in Rat Liver, Muscle, and Adipose Tissues

“…By contrast, AdipoR1 mRNA expression was enhanced in skeletal muscle while AdipoR2 mRNA was not significantly changed (Figure 4a,b). These results are consistent with previous studies that found a tissue-specific effect of lipid oversupply on adiponectin response and adiponectin receptors expression (21,27,31,32). It has been shown that insulin represses adiponectin receptor mRNA expression in both muscle and liver via activation of phosphatidylinositol 3-kinase and inactivation of Foxo1.…”

“…It has been shown that insulin represses adiponectin receptor mRNA expression in both muscle and liver via activation of phosphatidylinositol 3-kinase and inactivation of Foxo1. In contrast, other studies have shown a positive correlation between serum insulin levels and AdipoR1 expression in skeletal muscles (21). High-insulin levels in LE-treated rats observed here, may affect adiponectin receptor expression uniquely in different tissues.…”

“…The protein concentration was determined by the Bradford method (20). Aliquots of protein (100 µg) or immunoprecipitated proteins were then transferred to a nylon membrane and subjected to western blotting as previously described (21). Primary antibodies used were: AMPK, phospho-AMPK (Thr-172), ACC, phospho-ACC (Ser-79), LKB1, and p-LKB1 (Ser-428) obtained from Cell Signaling Technology (Beverly, MA), CaMKK and β-actin antibodies purchased from BD transduction laboratories (BD Pharmingen, San Jose, CA), phospho-insulin receptor substrate (Tyr-612) obtained from Biosource International (Camarillo, CA) and PGC1α antibody purchased from Abcam (Cambridge, UK).…”

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

“…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. An experiment using male C57BL/6J mice in experimental settings (age of mice and duration of the experiment) similar to the present study demonstrated that a high fat diet induced obesity with a significant reduction of Adipoq mRNA in the WAT while not affecting the plasma Adipoq (Barnea, 2006). The calories from fat in the HFD in the present study were 36%, whereas this was 42% in the study reported by Barnea.…”

Interactions between endocrine and circadian systems

“…In rodents, adiponectin peaks in the end of the light phase (inactive phase) and its rhythm is shifted under HFD (Ríos-Lugo et al 2010). Bullen and colleagues showed decreased adiponectin levels relative to fat mass following HFD in rodents (Barnea et al 2006, Bullen et al 2007. To assess the effect of adiponectin on the circadian clock, Hashinaga and colleagues used KK-Ta mice, a polygenic model of metabolic syndrome with hypoadiponectinemia.…”