Honokiol Improves Insulin Resistance, Hepatic Steatosis, and Inflammation in Type 2 Diabetic db/db Mice.

Young-Je Kim,Un Ju Jung

doi:10.3390/ijms20092303

Abstract

This study focuses on the effect of honokiol (HON) on glucose homeostasis, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db/db mice. Male C57BL/KsJ-db/db mice were fed a normal diet with or without HON (0.02%, w/w) or pioglitazone (PIO, anti-diabetic agent, 0.01%, w/w) for 5 weeks. Blood biomarker, tissue morphology and enzymatic and genetic parameters were determined. PIO significantly decreased food intake, fasting blood glucose, and glycosylated hemoglobin (HbA1c) levels, but markedly increased body weight, adipose tissue weight, and plasma leptin levels. HON did not significantly affect food intake, body weight, or levels of plasma leptin and blood glucose. However, HON led to significant decreases in adipose tissue weight, plasma insulin, blood HbA1c and HOMA-IR levels and improved glucose tolerance. The anti-diabetic and anti-adiposity effects of HON were partially related to the inhibition of gluconeogenic enzymes and their mRNA expression in the liver; and the inhibition of lipogenic enzymes in adipose tissue, respectively. Unlike PIO, HON did not affect dyslipidemia, but ameliorated hepatic steatosis by inhibiting hepatic lipogenic enzymes activity. Moreover, HON exhibited anti-inflammatory effects similar to PIO. These results suggest that HON can protect against type 2 diabetes by improving insulin resistance, glucose and lipid metabolism, and inflammation.

Highlights

The incidence of type 2 diabetes has increased in recent years [1]
This study investigated the effects of HON on hyperglycemia, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db/db mice – obesity-induced diabetic animals with insulin resistance
In obese diabetic db/db mice, PIO improved hyperglycemia, but induced lipid deposition in adipose tissues [20]. In agreement with this previous study, our study shows that PIO significantly decreases fasting blood glucose and blood HbA1c levels, but significantly increases body weight, fat weight, and plasma leptin levels, compared to control db/db mice

Summary

Introduction

The incidence of type 2 diabetes has increased in recent years [1]. Worldwide, approximately 1 in 11 adults have diabetes, 90% of which have type 2 diabetes. Obesity is a well-established risk factor for type 2 diabetes, and insulin resistance is a key link between obesity and type 2 diabetes [2,3]. The mechanism by which obesity causes insulin resistance is unclear, chronic inflammation in white adipose tissue and increased adiposity are linked to local and systemic insulin resistance [4,5,6,7]. Nonalcoholic fatty liver disease (NAFLD), which is characterized by an increase in intrahepatic triglyceride content with or without inflammation and fibrosis, is common in people with type 2 diabetes, and is highly correlated with the development and severity of insulin resistance [8,9,10]. Due to the complexity of obesity-related type 2 diabetes, the understanding of the pathogenic mechanisms that underlie the disease remain inadequate, and current therapeutics for improving type 2 diabetes are inefficient

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