2026-04-29T04:08:31Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/64942024-09-27T08:43:55Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Matesanz, Nuria author Bernardo, Edgar author Acin-Perez, Rebeca author Manieri, Elisa author Perez-Sieira, Sonia author Hernandez-Cosido, Lourdes author Montalvo-Romeral, Valle author Mora, Alfonso author Rodriguez, Elena author Leiva-Vega, Luis author Lechuga-Vieco, Ana V. author Ruiz-Cabello, Jesus author Torres, Jorge L author Crespo-Ruiz, Maria author Centeno, Francisco author Alvarez, Clara V. author Marcos, Miguel author Enriquez, Jose Antonio author Nogueiras, Ruben author Sabio, Guadalupe author 2017 Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that expression of the p38 MAPK activator MKK6 is elevated in white adipose tissue of obese individuals. Using knockout animals and shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic capacity of white adipose tissue, protecting mice against diet-induced obesity and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UCP1 expression in adipocytes, thereby increasing their thermogenic capacity. Mechanistically, we demonstrate that, in white adipose tissue, p38 is activated by an alternative pathway involving AMPK, TAK, and TAB. Our results identify MKK6 in adipocytes as a potential therapeutic target to reduce obesity. Nat Commun. 2017; 8(1):856 2041-1723 http://hdl.handle.net/20.500.12105/6494 29021624 10.1038/s41467-017-00948-z NATURE COMMUNICATIONS ACTIVATED PROTEIN-KINASE BODY-MASS INDEX INSULIN-RESISTANCE ADULT HUMANS ADAPTIVE THERMOGENESIS HUMAN ADIPOCYTES THYROID-FUNCTION MAP KINASE FAT GENE MKK6 controls T3-mediated browning of white adipose tissue