The Effects of High-fat-diet Combined with Chronic Unpredictable Mild Stress on Depression-like Behavior and Leptin/LepRb in Male Rats.

Jin Ling Yang,De Xiang Liu,Fang Pan,Cyrus Sh Ho,Hong Jiang,Roger Cm Ho

doi:10.1038/srep35239

Abstract

Leptin plays a key role in the pathogenesis of obesity and depression via the long form of leptin receptor (LepRb). An animal model of comorbid obesity and depression induced by high-fat diet (HFD) combined with chronic unpredictable mild stress (CUMS) was developed to study the relationship between depression/anxiety-like behavior, levels of plasma leptin and LepRb in the brains between four groups of rats, the combined obesity and CUMS (Co) group, the obese (Ob) group, the CUMS group and controls. Our results revealed that the Co group exhibited most severe depression-like behavior in the open field test (OFT), anxiety-like behavior in elevated plus maze test (EMT) and cognitive impairment in the Morris water maze (MWM). The Ob group had the highest weight and plasma leptin levels while the Co group had the lowest levels of protein of LepRb in the hypothalamus and hippocampus. Furthermore, depressive and anxiety-like behaviors as well as cognitive impairment were positively correlated with levels of LepRb protein and mRNA in the hippocampus and hypothalamus. The down-regulation of leptin/LepRb signaling might be associated with depressive-like behavior and cognitive impairment in obese rats facing chronic mild stress.

Highlights

Leptin is a hormone derived from adipose tissue that provides feedback about adiposity to the brain[20]
The leptin/LepRb signaling was tested subsequently to identify the levels of plasma leptin and expression of protein and mRNA of LepRb in the hippocampus and hypothalamus and their relationship with weight gain, depression/anxiety-like behavior and cognitive impairment in rats that were exposed to high-fat diet (HFD) and chronic unpredictable mild stress (CUMS), CUMS only, HFD only and the control group
The results show that consumption of the HFD induced higher body weight gain in the HFD groups compared with the regular diet (RD) groups

Summary

Introduction

Leptin is a hormone derived from adipose tissue that provides feedback about adiposity to the brain[20] It is circulated in blood, crosses the blood-brain barrier and exerts its effects on the leptin receptor, which are expressed in the hypothalamus, hippocampus and cerebral cortex[21]. Milaneschi et al demonstrated that the association between leptin and depressive symptoms was modulated by abdominal adiposity in humans but it was not possible to study the role of LepRb in humans[29]. The leptin/LepRb signaling was tested subsequently to identify the levels of plasma leptin and expression of protein and mRNA of LepRb in the hippocampus and hypothalamus and their relationship with weight gain, depression/anxiety-like behavior and cognitive impairment in rats that were exposed to HFD and CUMS, CUMS only, HFD only and the control group

Methods

Results

Conclusion