RT Journal Article
T1 Myeloid p38 activation maintains macrophage-liver crosstalk and BAT thermogenesis through IL-12-FGF21 axis
A1 Crespo, María
A1 Leiva Arjona, María Magdalena
A1 Sabio, Guadalupe
AB Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low-grade inflammation that contributes to the development of diabetes, steatosis, and insulin resistance. Recent research has shown that this chronic inflammation is crucially dependent on p38 pathway activity in macrophages, suggesting p38 inhibition as a possible treatment for obesity comorbidities. Nevertheless, we report here that lack of p38 activation in myeloid cells worsens high-fat diet-induced obesity, diabetes, and steatosis. Deficient p38 activation increases macrophage IL-12 production, leading to inhibition of hepatic FGF21 and reduction of thermogenesis in the brown fat. The implication of FGF21 in the phenotype was confirmed by its specific deletion in hepatocytes. We also found that IL-12 correlates with liver damage in human biopsies, indicating the translational potential of our results. Our findings suggest that myeloid p38 has a dual role in inflammation and that drugs targeting IL-12 might improve the homeostatic regulation of energy balance in response to metabolic stress.
PB Wolters Kluwer
SN 0270-9139
YR 2023
FD 2023-03-01
LK https://hdl.handle.net/20.500.14352/131350
UL https://hdl.handle.net/20.500.14352/131350
LA eng
NO Crespo, M. et al. (2023) «Myeloid p38 activation maintains macrophage-liver crosstalk and BAT thermogenesis through IL-12-FGF21 axis», Hepatology, 77(3), pp. 874-887.
NO IPP FP7 Marie Curie Programme
NO Centro Nacional de Investigaciones Cardiovasculares Carlos III
NO Comunidad Autónoma de Madrid
NO European Foundation for the Study of Diabetes
NO Fundación BBVA
NO Fundación Científica Asociación Española Contra el Cáncer
DS Docta Complutense
RD 18 mar 2026