Hippocampal Glycerol-3-Phosphate Acyltransferases 4 and BDNF in the Progress of Obesity-Induced Depression.

Yin-Qiong Huang,Keyue Hu,Shu Lin,Xia-Hong Lin,Yaofeng Wang

doi:10.3389/fendo.2021.667773

Abstract

BackgroundObesity has been reported to lead to increased incidence of depression. Glycerol-3-phosphate acyltransferases 4 (GPAT4) is involved in triacylglycerol synthesis and plays an important role in the occurrence of obesity. GPAT4 is the only one of GPAT family expressed in the brain. The aim of this study is to investigate if central GPAT4 is associated with obesity-related depression and its underlying mechanism.ResultsA high-fat diet resulted in increased body weight and blood lipid. HFD induced depression like behavior in the force swimming test, tail suspension test and sucrose preference test. HFD significantly up-regulated the expression of GPAT4 in hippocampus, IL-1β, IL-6, TNF-α and NF-κB, accompanied with down-regulation of BDNF expression in hippocampus and ventromedical hypothalamus, which was attributed to AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB).ConclusionOur findings suggest that hippocampal GPAT4 may participate in HFD induced depression through AMPK/CREB/BDNF pathway, which provides insights into a clinical target for obesity-associated depression intervention.

Highlights

Obesity is a metabolic disorder caused by excessive accumulation of fat due to increased energy intake
We found that 8 weeks of high-fat diet caused increased body weight (Figures 1A, B), and blood lipid level including total cholesterol (Figure 1C), low density lipoprotein (Figure 1D), and triglyceride (Figure 1E), compared with normal diet (ND) group
We found that compared with ND group, Glycerol-3-phosphate acyltransferases 4 (GPAT4) mRNA expression in hippocampus was significantly upregulated in high-fat diet (HFD) group (Figure 3A)

Summary

Introduction

Obesity is a metabolic disorder caused by excessive accumulation of fat due to increased energy intake. Both environmental factors and genetic factors are responsible for the development of obesity [1, 2]. The main clinical consequences of obesity include diabetes, cardiovascular disease, respiratory distress syndrome, sleep disorders, asthma, and tumors, as well as various mental and psychological diseases [3, 4]. Both epidemiological and clinical studies have shown that there is a positive correlation between obesity and depression. The aim of this study is to investigate if central GPAT4 is associated with obesity-related depression and its underlying mechanism

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Results

Conclusion