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Prolonged breastfeeding protects from obesity by hypothalamic action of hepatic FGF21

2022; Nature Portfolio; Volume: 4; Issue: 7 Linguagem: Inglês

10.1038/s42255-022-00602-z

2522-5812

Verónica Pena-León, Cintia Folgueira, Silvia Barja-Fernández, Raquel Pérez-Lois, Natália da Silva Lima, Marion Martin, Violeta Heras, Sara Martínez-Martínez, Paola Valero, Cristina Iglesias, Manon Duquenne, Omar Al–Massadi, Daniel Beiroa, Yara Souto, Miguel Fidalgo, Sowmyalakshmí Rasika, Diana Guallar, Juan Cuñarro, Cecilia Castelao, Ana Senra, Patricia González-Sáenz, Rocío Vázquez‐Cobela, Rosaura Leis, Guadalupe Sabio, Helge Müller‐Fielitz, Markus Schwaninger, Miguel López, Sulay Tovar, Felipe F. Casanueva, Emmanuel Valjent, Carlos Diéguez, Vincent Prévot, Rubén Nogueiras, Luísa M. Seoane,

Adipose Tissue and Metabolism

Abstract Early-life determinants are thought to be a major factor in the rapid increase of obesity. However, while maternal nutrition has been extensively studied, the effects of breastfeeding by the infant on the reprogramming of energy balance in childhood and throughout adulthood remain largely unknown. Here we show that delayed weaning in rat pups protects them against diet-induced obesity in adulthood, through enhanced brown adipose tissue thermogenesis and energy expenditure. In-depth metabolic phenotyping in this rat model as well as in transgenic mice reveals that the effects of prolonged suckling are mediated by increased hepatic fibroblast growth factor 21 (FGF21) production and tanycyte-controlled access to the hypothalamus in adulthood. Specifically, FGF21 activates GABA-containing neurons expressing dopamine receptor 2 in the lateral hypothalamic area and zona incerta. Prolonged breastfeeding thus constitutes a protective mechanism against obesity by affecting long-lasting physiological changes in liver-to-hypothalamus communication and hypothalamic metabolic regulation.