Aging Differentially Effects Diet-Induced Obesity and Central Leptin Sensitivity in Rats

Lynda M Brown,Paula T Cooney,Keshia R Ladmirault

doi:10.23953/cloud.ijanhs.136

Abstract

In this study we examined whether sex differences in central leptin sensitive young rats disappears in middle-aged rats. As animals age, many gain visceral fat and develop leptin resistance, making them more susceptible to inflammation. Middle-aged rats were fed low-fat (LF) or high-fat (HF) diets for 2 months and during this time were given intra-3 rd -ventricular (i3vt) leptin injections in a range of doses. Females had a dose dependent decrease in food intake (FI) in response to i3vt leptin. Males reduced FI after i3vt injection of 5.0 μg leptin but not at any other dose. There was also a higher expression of hypothalamic cytokines that are part of the inflammation cascade in males including IL6, TNFα and XBP1. Females remained sensitive to i3vt leptin and had lower hypothalamic cytokine expression than males. The female rats in both diets had visceral fat percentages similar to that of the males which may mean that age increases fat in this depot in rats. These data indicate that middle-aged rats are in a transition period in terms of hormonal sensitivity that may serve as a model to study age-associated changes. Response patterns in female rats that are cycling but have not reached persistent estrous may be suggestive for explanations of physiological changes in perimenopausal women. These findings are important because aging represents a time when health is impacted by diet, body fat distribution and estrogen levels.

Highlights

There are several factors that interact in obesity that are part of the current experimental design including sex, diet and age
Central leptin injections reduce food intake and body weight; effects that are dependent upon sex, diet and age
When young-adult (3-month old) Long Evans rats are given i3vt leptin, males respond at higher doses than females indicating that males are less sensitive to central leptin than females [15, 16]

Summary

Introduction

There are several factors that interact in obesity that are part of the current experimental design including sex, diet and age. Consuming high-fat (HF) foods is one of the most important environmental factors leading to obesity [1]. Ingestion of a HF diet leads to hypothalamic leptin and insulin resistance [2, 3]. Obesity is accompanied by chronic inflammation, which is causally linked to leptin and insulin resistance [4,5,6] and may result in obesity. When a diet high in saturated fat is consumed free fatty acids (FFAs) increase inflammation by activating toll-like receptor 4 (TLR4) [7]. Chronic activation of pro-inflammatory pathways may be at least partly responsible for obesity-induced insulin resistance and diabetes [4,5,6].

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