Allomyrina dichotoma Larva Extract Ameliorates the Hepatic Insulin Resistance of High-Fat Diet-Induced Diabetic Mice.

Kyong Kim,Minho Lee,Chul Young Kim,Yoon Sin Oh,Eun-Young Park,Hee-Sook Jun,Dong Jae Baek,Gong Deuk Bae

doi:10.3390/nu11071522

Abstract

Allomyrina dichotoma larva is a nutritional-worthy future food resource and it contributes to multiple pharmacological functions. However, its antidiabetic effect and molecular mechanisms are not yet fully understood. Therefore, we investigated the hypolipidemic effect of A. dichotoma larva extract (ADLE) in a high-fat diet (HFD)-induced C57BL/6J mice model. Glucose tolerance and insulin sensitivity in HFD-induced diabetic mice significantly improved after ADLE administration for six weeks. The levels of serum triglyceride (TG), aspartate aminotransferase (AST), alanine transferase (ALT) activity, and lipid accumulation were increased in the liver of HFD-fed mice, but the levels were significantly reduced by the ADLE treatment. Moreover, hepatic fibrosis and inflammatory gene expression in the liver from HFD-treated mice were ameliorated by the ADLE treatment. Dephosphorylation of AMP-activated protein kinase (AMPK) by palmitate was inhibited in the ADLE treated HepG2 cells, and subsequently reduced expression of lipogenic genes, such as SREPBP-1c, ACC, and FAS were observed. The reduced expression of lipogenic genes and an increased phosphorylation of AMPK was also observed in the liver from diabetic mice treated with ADLE. In conclusion, ADLE ameliorates hyperlipidemia through inhibition of hepatic lipogenesis via activating the AMPK signaling pathway. These findings suggest that ADLE and its constituent bioactive compounds are valuable to prevent or treat hepatic insulin resistance in type 2 diabetes.

Highlights

Nonalcoholic fatty liver disease (NAFLD), or fatty liver, is a chronic liver disease associated with hepatic dysfunction due to excessive triglyceride (TG) accumulation [1]
The high-fat diet (HFD) was administered to C57BL/6J mice for six weeks to induce type 2 diabetes
2.3-fold as compared with the normal-fat diet (NFD) group (p < 0.001), whereas food intake decreased in the HFD group

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD), or fatty liver, is a chronic liver disease associated with hepatic dysfunction due to excessive triglyceride (TG) accumulation [1]. NAFLD is closely related to metabolic diseases, such as obesity, insulin resistance, hypertension, and dyslipidemia, and the incidence of NAFLD increases as obesity increases [2]. Abnormal dietary fat intake directly contributes to a casual role in hepatic lipid accumulation, such as TG, cholesterol, and lipid droplets. Nutrients 2019, 11, 1522 in the cytoplasm of hepatocytes [3], and lipotoxicity that is caused by fat accumulation induces hepatic insulin resistance in the pathogenesis of type 2 diabetes [4]. According to the Food and Agriculture Organization of the United Nations, edible insects have been reported to be possible future human dietary supplements because they are a rich source of unsaturated fatty acids, proteins, minerals, vitamins, and other nutrients [6,7,8]

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