Abstract

The demand for meta-analyses in basic biomedical research has been increasing because the phenotyping of genetically modified mice does not always produce consistent results. Melanin-concentrating hormone (MCH) has been reported to be involved in a variety of behaviors that include feeding, body-weight regulation, anxiety, sleep, and reward behavior. However, the reported behavioral and metabolic characteristics of MCH signaling-deficient mice, such as MCH-deficient mice and MCH receptor 1 (MCHR1)-deficient mice, are not consistent with each other. In the present study, we performed a meta-analysis of the published data related to MCH-deficient and MCHR1-deficient mice to obtain robust conclusions about the role of MCH signaling. Overall, the meta-analysis revealed that the deletion of MCH signaling enhanced wakefulness, locomotor activity, aggression, and male sexual behavior and that MCH signaling deficiency suppressed non-REM sleep, anxiety, responses to novelty, startle responses, and conditioned place preferences. In contrast to the acute orexigenic effect of MCH, MCH signaling deficiency significantly increased food intake. Overall, the meta-analysis also revealed that the deletion of MCH signaling suppressed the body weight, fat mass, and plasma leptin, while MCH signaling deficiency increased the body temperature, oxygen consumption, heart rate, and mean arterial pressure. The lean phenotype of the MCH signaling-deficient mice was also confirmed in separate meta-analyses that were specific to sex and background strain (i.e., C57BL/6 and 129Sv). MCH signaling deficiency caused a weak anxiolytic effect as assessed with the elevated plus maze and the open field test but also caused a weak anxiogenic effect as assessed with the emergence test. MCH signaling-deficient mice also exhibited increased plasma corticosterone under non-stressed conditions, which suggests enhanced activity of the hypothalamic-pituitary-adrenal axis. To the best of our knowledge, the present work is the first study to systematically compare the effects of MCH signaling on behavioral and metabolic phenotypes.

Highlights

  • Meta-analysis is a statistical method of combining the results of individual studies to obtain the most reliable conclusions [1]

  • Melanin-concentrating hormone (MCH) is a 17-amino-acid cyclic neuropeptide that was originally isolated from teleost fish; in these fish, MCH causes the aggregation of melanosomes in the scales, which results in color changes [3]

  • The Role of MCH Signaling in Feeding Behavior Nearly two decades ago and long after the report of the expression of MCH in the mammalian lateral hypothalamus [35], Qu et al reported the orexigenic effect of MCH [4]

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Summary

Introduction

Meta-analysis is a statistical method of combining the results of individual studies to obtain the most reliable conclusions [1]. The use of meta-analysis in basic biomedical research is rare, the demand has been increasing because many researchers are working on genetically modified mice to examine the roles of genes in animal behavior and metabolism, and the results of the behavioral studies are not always consistent across research laboratories [2]. MCH expression is restricted to the lateral hypothalamus of the brain, and MCH is not expressed outside of the brain. Analyses of the gene expressions in the hypothalamus of leptin-deficient mice have revealed the orexigenic effect of MCH in mammals [4]. In contrast to the restricted localization of MCH neurons in the lateral hypothalamic area and the zona incerta, MCH neurons send their projections broadly across the brain, and MCHR1

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