Peripherally administered melanocortins induce mice fat browning and prevent obesity

• Published in: International Journal of Obesity Vol. 43; no. 5; pp. 1058 - 1069
• Main Authors: Rodrigues, Adriana R., Salazar, Maria J., Rocha-Rodrigues, Sílvia, Gonçalves, Inês O., Cruz, Célia, Neves, Delminda, Almeida, Henrique, Magalhães, José, Gouveia, Alexandra M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2019; Nature Publishing Group
• Subjects: 13/51; 14/63; 3T3-L1 Cells; 64/60; 692/163/2743/393; 692/699/2743/393; 82/29; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipose tissue; Adipose tissue (brown); Adipose Tissue, Beige - drug effects; Adipose Tissue, Beige - metabolism; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Animals; Appetite; Biosynthesis; Body fat; Body weight; Browning; Cells, Cultured; Central nervous system; Diet; Diet, High-Fat; Epidemiology; Food intake; Gene expression; Glucose; Health aspects; Health Promotion and Disease Prevention; Homeostasis; Hormones; Insulin; Insulin resistance; Internal Medicine; Laboratory rats; Lipids; Medicine; Medicine & Public Health; Melanocortin; Melanocortins - pharmacology; Melanocyte stimulating hormone; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mitochondria; Neuropeptides; Obesity; Obesity - metabolism; Obesity - prevention & control; Oxygen consumption; Phenotypes; Prevention; Public Health; Regulators; Respiration; Respiratory rate; Thermogenesis - drug effects; Thermogenesis - physiology
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-018-0155-5

Background/objectives The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. Methods The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. Results Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. Conclusions This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.