Hypothalamic astrocytic-BMAL1 regulates energy homeostasis in a sex-dependent manner
María Luengo-Mateos,
Antía González-Vila,
Nathalia Romanelli Vicente Dragano,
Nataliia Ohinska,
María Silveira-Loureiro,
Marco González-Domínguez,
Ánxela Estévez-Salguero,
Paula Novelle-Rodríguez,
Miguel López,
Olga Barca-Mayo
Affiliations
María Luengo-Mateos
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Antía González-Vila
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Nathalia Romanelli Vicente Dragano
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain
Nataliia Ohinska
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
María Silveira-Loureiro
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Marco González-Domínguez
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Ánxela Estévez-Salguero
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Paula Novelle-Rodríguez
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Miguel López
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain; Corresponding author
Olga Barca-Mayo
Physiology Department, Molecular Medicine, and Chronic Diseases Research Centre (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Corresponding author
Summary: Here, we demonstrate that hypothalamic astrocytic BMAL1 computes cyclic metabolic information to optimize energetic resources in a sexually dimorphic manner. Knockdown of BMAL1 in female astrocytes leads to negative energy balance and alters basal metabolic cycles without affecting circadian locomotor activity. Thus, astrocytic BMAL1 contributes to the control of energy balance through the modulation of the metabolic rate, hepatic and white adipose tissue lipogenesis, and the activity of brown adipose tissue. Importantly, most of these alterations are specific to hypothalamic astrocytic BMAL1. Moreover, female mice with BMAL1 knockdown in astrocytes exhibited a “male-like” metabolic obese phenotype when fed a high-fat diet. Overall, our results suggest a sexually dimorphic effect of astrocytic BMAL1 on the regulation of energy homeostasis, which may be of interest in the physiopathology of obesity and related comorbidities.
