Adiponectin induced AMP-activated protein kinase impairment mediates insulin resistance in Bama mini-pig fed high-fat and high-sucrose diet.

Miaomiao Niu,Jifang Yuan,Yuqiong Zhao,Lei Xiang,Xin Dai,Hua Chen,Yaqian Liu

doi:10.5713/ajas.17.0006

Abstract

ObjectiveAdipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs.MethodsAn obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor necrosis factor alpha (TNF-α), and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed by Pearce’s correlation analysis.ResultsObese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and TNF-α showed no difference, while the values of TNF-α in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained.ConclusionAMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable model for human metabolic diseases.

Highlights

The prevalence rate of obesity has rapidly increased globally in the last two decades, reaching epidemic proportions [1,2,3]
Intravenous glucose tolerance test (IVGTT) results showed that glucose levels were higher in obese pigs compared with the lean group at all time points (p
Plasma glucose levels in obese pigs remained high for the whole course of IVGTT, while readily returning to normal in lean animals

Summary

Introduction

The prevalence rate of obesity has rapidly increased globally in the last two decades, reaching epidemic proportions [1,2,3] Numerous studies in both animal models and humans have demonstrated that abnormal adipose tissue accumulation may result in metabolic disorders that cause severe insulin resistance (IR) and type 2 diabetes [4]. Adipose tissue is no longer considered an inert organ for lipid storage and mobilization, but instead thought to play an active role in regulating insulin effects, whole-body energy metabolism, and homeostasis, primarily through its endocrine function [5,6,7,8]. Adipose tissue secretes a number of adipokines, including leptin and adiponectin, and constitutes a major source of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), mediating obesity-related www.ajas.info

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