Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6494
MKK6 controls T3-mediated browning of white adipose tissue
Matesanz, Nuria CNIC | Bernardo, Edgar CNIC | Acin-Perez, Rebeca CNIC | Manieri, Elisa CNIC | Perez-Sieira, Sonia | Hernandez-Cosido, Lourdes | Montalvo-Romeral, Valle CNIC | Mora, Alfonso CNIC | Rodriguez, Elena CNIC | Leiva-Vega, Luis CNIC | Lechuga-Vieco, Ana V. CNIC | Ruiz-Cabello, Jesus CNIC | Torres, Jorge L | Crespo-Ruiz, Maria CNIC | Centeno, Francisco | Alvarez, Clara V. | Marcos, Miguel | Enriquez, José Antonio CNIC | Nogueiras, Ruben | Sabio, Guadalupe CNIC
Nat Commun. 2017; 8(1):856
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.
ACTIVATED PROTEIN-KINASE | BODY-MASS INDEX | INSULIN-RESISTANCE | ADULT HUMANS | ADAPTIVE THERMOGENESIS | HUMAN ADIPOCYTES | THYROID-FUNCTION | MAP KINASE | FAT | GENE