Metabolic and genomic adaptations to winter fattening in a primate species, the grey mouse lemur (Microcebus murinus)

• Published in: International Journal of Obesity 2018-02, Vol.42 (2), p.221-230
• Main Authors: Terrien, J, Gaudubois, M, Champeval, D, Zaninotto, V, Roger, L, Riou, J F, Aujard, F
• Format: Article
• Language: English
• Subjects: 631/443/319/1557; 631/443/319/1642/393; 631/443/319/2723; 692/163/2743/393; Adaptation; Adaptation, Physiological - genetics; Adaptation, Physiological - physiology; Adipose tissue; Adipose tissue (brown); Animal biology; Animal models; Animals; Annual variations; Behavior, Animal - physiology; Body mass; Body Temperature - genetics; Body Temperature - physiology; Body weight; Cell metabolism; Cheirogaleidae - genetics; Cheirogaleidae - metabolism; Cholesterol; Cold Temperature; Cold weather; Development and progression; Energy Metabolism - genetics; Energy Metabolism - physiology; Environmental changes; Epidemiology; Flexibility; Food and nutrition; Food habits; Food intake; Gene expression; Genomics; Health aspects; Health Promotion and Disease Prevention; Homeostasis; Hot Temperature; Inflammation; Insulin; Internal Medicine; Lemurs; Life Sciences; Lipid metabolism; Lipid peroxidation; Liver; Liver - metabolism; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Microcebus murinus; Models, Animal; Obesity; original-article; Oxidation; Oxidative Stress; Physiology; Public Health; Regulations; Seasonal variations; Seasons; Signaling; Tumor necrosis factor; Weight Gain - genetics; Weight Gain - physiology; Weight Loss - genetics; Weight Loss - physiology; Winter
• ISSN: 0307-0565; 1476-5497; 0307-0565
• DOI: 10.1038/ijo.2017.195

Aim: To understand the mechanisms underlying the development of metabolic changes leading to obesity remains a major world health issue. Among such mechanisms, seasonality is quite underestimated although it corresponds to the manifestation of extreme metabolic flexibility in response to a changing environment. Nevertheless, the changes induced by such flexibility are far to be understood, especially at the level of insulin signaling, genomic stability or inflammation. Methods: Here, we investigated the metabolic regulations displayed by a seasonal primate species, the grey mouse lemur ( Microcebus murinus ) that exhibits pronounced changes in body mass during the 6-month winter season: a fattening period followed by a spontaneous fat loss, without ever reaching pathological stages. Results: Such body weight modulations result from a combination of behavioral (food intake) and physiological (endocrine changes, switch between carb and lipid oxidation) adjustments that spontaneously operate during winter. Conversely to classical models of obesity, insulin sensitivity is paradoxically preserved during the obesogenic phase. Fat loss is associated with increased metabolic activity, especially in brown adipose tissue, and induced increased oxidative stress associated with telomere length dynamic. Furthermore, liver gene expression analysis revealed regulations in metabolic homeostasis (beta-oxidation, insulin signaling, cholesterol and lipid metabolism) but not for genes involved in inflammatory process (for example, Ifng, Tnf, Nfkb1 ). Conclusion: Altogether, these results show that mouse lemurs undergo deep physiological and genomic seasonal changes, without ever reaching a pathological stage. Further investigation is needed to decipher the underlying mechanisms, which may well be highly relevant for human therapeutic strategies.