Sex and estrogens alter the action of glucagon-like peptide-1 on reward.

Jennifer E Richard,Lorena López-Ferreras,Rozita H Anderberg,Karolina P Skibicka,Kajsa Olandersson

doi:10.1186/s13293-016-0059-9

Jennifer E Richard, Lorena López-Ferreras + Show 3 more

Open Access

https://doi.org/10.1186/s13293-016-0059-9

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Journal: Biology of sex differences	Publication Date: Jan 16, 2016
Citations: 115	License type: cc-by

Affiliation: University of Gothenburg

Abstract

BackgroundFeeding behavior is regulated through an intricate array of anorexic and orexigenic hormones acting on the central nervous system (CNS). Some of these hormones may have differential effects in males and females, effects potentially attributed to actions of gonadal steroids, especially estrogens. Central stimulation of the glucagon-like peptide-1 (GLP-1) receptors reduces feeding and food-reward behavior by acting on CNS regions important for the anorexic actions of estrogens. Thus, we propose that the action of GLP-1 on food intake and reward may differ between sexes.MethodsMale and female rats were centrally injected with the GLP-1 analog exendin-4 (Ex4) in a non-deprived or food-restricted state; reward behavior was measured in a progressive ratio operant conditioning task. Intake of chow and palatable food were also measured. To determine if sex differences in the actions of Ex4 are due to interactions with estrogens, Ex4 treatment was preceded by treatment with a nonselective estrogen receptor-α (ERα) and ERβ or ERα-selective antagonist.ResultsCentral injection of Ex4 revealed increased reward behavior suppression in females, compared to males, in the operant conditioning task. This increase was present in both non-deprived and food-restricted animals with larger differences in the fed state. Intake of chow and palatable food, after Ex4, were similar in males and females. Food reward, but not food intake, effect of Ex4 was attenuated by pretreatment with ER antagonist in both sexes, suggesting that estrogens may modulate effects of Ex4 in both sexes. Furthermore, central pretreatment with ERα-selective antagonist was sufficient to attenuate effects of Ex4 on reward.ConclusionsCollectively, these data reveal that females display much higher sensitivity to the food reward impact of central GLP-1 receptor activation. Surprisingly, they also demonstrate that central ERα signaling is necessary for the actions of GLP-1 on food-reward behavior in both sexes.

Highlights

Feeding behavior is regulated through an intricate array of anorexic and orexigenic hormones acting on the central nervous system (CNS)
Two-way repeated measures ANOVA revealed a significant reduction in sucrose rewards earned, and lever presses for sucrose, at both doses of Ex4 in female, but not male, rats (Holm-Sidak’s multiple comparisons test, p < 0.0001; Fig. 1a, c)
Data displayed as sucrose rewards earned and active lever presses in percent of vehicle value revealed significant differences for both parameters at both doses of Ex4 between males and females (p < 0.05, Fig. 1b; p < 0.05, Fig. 1d)

Summary

Introduction

Feeding behavior is regulated through an intricate array of anorexic and orexigenic hormones acting on the central nervous system (CNS) Some of these hormones may have differential effects in males and females, effects potentially attributed to actions of gonadal steroids, especially estrogens. Despite the overrepresentation of women in diseases resulting from disordered eating [1, 2], few preclinical studies have a clear focus to explore the neurobiology and physiology of food intake regulation in females. This sex gap is symptomatic of what is seen in preclinical medical research overall.

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