A small amount of dietary carbohydrate can promote the HFD-induced insulin resistance to a maximal level.

Shuang Mei,Haihua Gu,Huailan Guo,Zhenqi Liu,Xuefeng Li,Longying Zha,Wenhong Cao,Xuefeng Yang,Junwei Cai,Brian J Bennett,Ling He

doi:10.1371/journal.pone.0100875

Abstract

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1–25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level.

Highlights

Obesity is closely associated with insulin resistance, which is a necessary precursor and component of type 2 diabetes mellitus (T2DM)
Some studies have shown that carb-rich diets promote development of insulin resistance and T2DM [17,18] while others have shown that high-carb diet is protective against insulin resistance and T2DM compared to HFD [19], and low-carb diet is not necessarily protective against insulin resistance and diabetes [20,21]
Triglyceride (TG), and free fatty acids (FFA) were increased in all groups of HFD as usual. These results show that dietary carbs are not essential for the HFD-induced body fat gain but can enhance the HFD-induced body fat gain in a dosedependent manner, and a very small amount of carbs (10%) in the HFD can cause the maximal level of body weight gain

Summary

Introduction

Obesity is closely associated with insulin resistance, which is a necessary precursor and component of type 2 diabetes mellitus (T2DM). That means that insulin resistance is an essential precursor of many major health problems associated with T2DM. Some studies have shown that carb-rich diets promote development of insulin resistance and T2DM [17,18] while others have shown that high-carb diet is protective against insulin resistance and T2DM compared to HFD [19], and low-carb diet is not necessarily protective against insulin resistance and diabetes [20,21]. These conflicting results demonstrate the complexity and difficulty in defining the role of each dietary component in insulin resistance and T2DM. Are dietary carbs necessary for the HFD-induced insulin resistance? Second, how much carb is too much or sufficient to promote the HFD-induced insulin resistance? Third, is fat essential for insulin resistance? In this study, we addressed these questions and the associated mechanisms

Objectives

Results

Conclusion