Abstract

Investigations into the mechanisms regulating obesity are frantic and novel translational approaches are needed. The raccoon dog (Nyctereutes procyonoides) is a canid species representing a promising model to study metabolic regulation in a species undergoing cycles of seasonal obesity and fasting. To understand the molecular mechanisms of metabolic regulation in seasonal adaptation, we analyzed key central nervous system and peripheral signals regulating food intake and metabolism from raccoon dogs after autumnal fattening and winter fasting. Expressions of neuropeptide Y (NPY), orexin-2 receptor (OX2R), pro-opiomelanocortin (POMC) and leptin receptor (ObRb) were analyzed as examples of orexigenic and anorexigenic signals using qRT-PCR from raccoon dog hypothalamus samples. Plasma metabolic profiles were measured with 1H NMR-spectroscopy and LC-MS. Circulating hormones and cytokines were determined with canine specific antibody assays. Surprisingly, NPY and POMC were not affected by the winter fasting nor autumn fattening and the metabolic profiles showed a remarkable equilibrium, indicating conserved homeostasis. However, OX2R and ObRb expression changes suggested seasonal regulation. Circulating cytokine levels were not increased, demonstrating that the autumn fattening did not induce subacute inflammation. Thus, the raccoon dog developed seasonal regulatory mechanisms to accommodate the autumnal fattening and prolonged fasting making the species unique in coping with the extreme environmental challenges.

Highlights

  • A lack of food sources is a common challenge for wild animals and surviving in such conditions requires resilience to fasting periods, saving energy by the hypometabolism and storing energy as food caches or as adipose tissue in the body

  • In order to test the hypothesis, we investigated the role of key central nervous system food intake regulators and the impact on the metabolome during autumnal fattening and prolonged winter fasting in the raccoon dog

  • The two winter groups exhibited differences in hypothalamic orexin-2 receptor (OX2R) and ObRb compared with the winter groups exhibited differences in hypothalamic OX2R and ObRb compared with autumn group, indicating seasonal regulation, whereas the effects of the prolonged tenthe autumn group, indicating seasonal regulation, whereas the effects of the prolonged week fasting period showed a weaker response despite the significantly lower body ten-week fasting period showed a weaker response despite the significantly lower body weight of the animals

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Summary

Introduction

A lack of food sources is a common challenge for wild animals and surviving in such conditions requires resilience to fasting periods, saving energy by the hypometabolism and storing energy as food caches or as adipose tissue in the body. Today mankind is facing the opposite problem as high energy food sources are available, lifestyles have changed to be less strenuous and the physical activity intensity is reduced. Adipose tissue is accumulated in an excessive manner, causing these adverse health effects [1,2,3,4,5]. In nature some animal species repeatedly undergo non-pathological large-scale fluctuations in their body fat storages and energy metabolism as a part of their natural seasonal cycles without major adverse effects to their health. It is prudent to investigate the molecular mechanisms regulating these opposite metabolic states

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