RT Journal Article
T1 Specific knockout of p85α in brown adipose tissue induces resistance to high-fat diet–induced obesity and its metabolic complications in male mice
A1 Gómez Hernández, María De La Almudena
A1 Raposo López-Pastor, Andrea
A1 Rubio-Longas, Carlota
A1 Majewski, Patrik
A1 Beneit, Nuria
A1 Viana-Huete, Vanesa
A1 García-Gómez, Gema
A1 Fernandez, Silvia
A1 Hribal, Marta Letizia
A1 Sesti, Giorgio
A1 Escribano Illanes, Óscar
A1 Benito De Las Heras, Manuel R.
AB Objective: An increase in mass and/or brown adipose tissue (BAT) functionality leads to an increase in energy expenditure, which may be beneficial for the prevention and treatment of obesity. Moreover, distinct class I PI3K isoforms can participate in metabolic control as well as in systemic dysfunctions associated with obesity. In this regard, we analyzed in vivo whether the lack of p85a in BAT (BATp85aKO) could modulate the activity and insulin signaling of this tissue, thereby improving diet-induced obesity and its associated metabolic complications.Methods: We generated BATp85aKO mice using Cre-LoxP technology, specifically deleting p85a in a conditional manner. To characterize thisnew mouse model, we used mice of 6 and 12 months of age. In addition, BATp85aKO mice were submitted to a high-fat diet (HFD) to challengeBAT functionality.Results: Our results suggest that the loss of p85a in BAT improves its thermogenic functionality, high-fat dieteinduced adiposity and bodyweight, insulin resistance, and liver steatosis. The potential mechanisms involved in the improvement of obesity include (1) increased insulin signaling and lower activation of JNK in BAT, (2) enhanced insulin receptor isoform B (IRB) expression and association with IRS-1 in BAT, (3) lower production of proinflammatory cytokines by the adipose organ, (4) increased iWAT browning, and (5) improved liver steatosis.Conclusions: Our results provide new mechanisms involved in the resistance to obesity development, supporting the hypothesis that the gain of BAT activity induced by the lack of p85a has a direct impact on the prevention of diet-induced obesity and its associated metabolic complications
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/93418
UL https://hdl.handle.net/20.500.14352/93418
LA eng
NO Gomez-Hernandez A, Lopez-Pastor AR, Rubio-Longas C, Majewski P, Beneit N, Viana-Huete V, et al. Specific knockout of p85α in brown adipose tissue induces resistance to high-fat diet–induced obesity and its metabolic complications in male mice. Molecular Metabolism 2020;31:1–13. https://doi.org/10.1016/j.molmet.2019.10.010.
NO Ministerio de Ciencia e Innovación (España)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III
NO Centro de Investigación Biomédica de Diabetes y Enfermedades Metabólicas Asociadas 
DS Docta Complutense
RD 12 abr 2025