Changes of fat-mass and obesity-associated protein expression in the hippocampus in animal models of high-fat diet-induced obesity and D-galactose-induced aging

Min Soo Kang,Woosuk Kim,Dae Won Kim,Hyo Young Jung,Tae Hyeong Kim,In Koo Hwang,Hyun Jung Kwon,Jung Hoon Choi

doi:10.1186/s42826-020-00046-0

Abstract

Fat-mass and obesity-associated protein (Fto) is highly expressed in the brain including, the hippocampus, and its expression is significantly decreased in the brain of Alzheimer’s disease patients. In the present study, we measured Fto immunoreactivity and protein levels in the hippocampus of obese and aged mice, which were induced by high-fat diet for 12 weeks and D-galactose treatment for 10 weeks, respectively. The obesity and aging phenotypes were assessed by physiological parameters and Morris water maze test, respectively. High fat diet fed mice showed significant increases in body weight and blood glucose levels compared to that in the control or D-galactose-induced aged mice. In addition, treatment with D-galactose significantly decreased the spatial memory. Fto immunoreactivity in the control group was mainly detected in the pyramidal cells of the CA1 and CA3 regions and in the granule cells of the dentate gyrus. In the hippocampus of high-fat diet-fed mice, Fto immunoreactive structures were similarly found in the hippocampus compared to that in the control group, but Fto immunoreactivity in high-fat diet-fed mice was also found in the stratum oriens and radiatum of the CA1 and CA3 regions and the polymorphic layer of the dentate gyrus. In the hippocampus of D-galactose-induced aged mice, fewer Fto immunoreactive structures were detected in the granule cell layer of the dentate gyrus compared to the control group. Fto mRNA and protein levels based on quantitative real-time polymerase chain reaction and western blot assays were slightly increased in the hippocampus of high-fat diet-fed mice compared to that in control mice. In addition, Fto mRNA and protein levels were significantly decreased in the aged hippocampus compared to that in the control group. Fto protein levels are susceptible to the aging process, but not in the hippocampus of high-fat diet-induced obesity. The reduction of Fto in aged mice may be associated with reduced memory impairment in mice.

Highlights

Overweight/obesity and aging are the most threatening factors in human beings and about one fourth of the population in the world will be affected by overweight or obesity in 2030 [1]
We found that obese and aged animals induced by high-fat diet (HFD) feeding for 4 or 12 weeks and D-galactose treatment for 7 weeks show less proliferating cells and differentiated neuroblasts in the dentate gyrus compared to mice in control group [16,17,18,19]
We investigated the localization of fat-mass and obesity-associated (Fto) immunoreactivity, protein and mRNA levels in the hippocampus of obese and aged mice to elucidate the role of Fto in the hippocampus of these animals

Summary

Introduction

Overweight/obesity and aging are the most threatening factors in human beings and about one fourth of the population in the world will be affected by overweight or obesity in 2030 [1]. The fat-mass and obesity-associated (Fto) gene is located on chromosome 16 (16q12.2) and controls energy balance, food intake, and lipid metabolism in the body [2]. Fto is strongly associated with obesity [3] and aging [4]. Overexpression of Fto leads to increases in body and fat mass [5] and modulates the mitotic clonal expansion of adipose tissue in obese mice [6]. Mice with knockout or missense mutations of Fto have a lean phenotype with or without growth retardation [7, 8]

Methods

Results

Discussion

Conclusion