RT Journal Article
T1 CB1 blockade potentiates down-regulation of lipogenic gene expression in perirenal adipose tissue in high carbohydrate diet-induced obesity.
A1 Vida, Margarita
A1 Rivera, Patricia
A1 Gavito, Ana Luisa
A1 Suárez, Juan
A1 Pavón, Francisco Javier
A1 Arrabal, Sergio
A1 Romero-Cuevas, Miguel
A1 Bautista, Dolores
A1 Martínez, Ana
A1 Rodríguez de Fonseca, Fernando
A1 Serrano, Antonia
A1 Baixeras, Elena
K1 Tejido adiposo blanco
K1 Alimentación rica en grasa
K1 Carbohidratos dietéticos
K1 Riñón
K1 Lipogénesis
K1 Peso corporal
K1 Obesidad
AB De novo lipogenesis and hypercaloric diets are thought to contribute to increased fat mass, particularly in abdominal fat depots. CB1 is highly expressed in adipose tissue, and CB1-mediated signalling is associated with stimulation of lipogenesis and diet-induced obesity, though its contribution to increasing fat deposition in adipose tissue is controversial. Lipogenesis is regulated by transcription factors such as liver X receptor (LXR), sterol-response element binding protein (SREBP) and carbohydrate-responsive-element-binding protein (ChREBP). We evaluated the role of CB1 in the gene expression of these factors and their target genes in relation to lipogenesis in the perirenal adipose tissue (PrAT) of rats fed a high-carbohydrate diet (HCHD) or a high-fat diet (HFD). Both obesity models showed an up-regulated gene expression of CB1 and Lxrα in this adipose pad. The Srebf-1 and ChREBP gene expressions were down-regulated in HFD but not in HCHD. The expression of their target genes encoding for lipogenic enzymes showed a decrease in diet-induced obesity and was particularly dramatic in HFD. In HCHD, CB1 blockade by AM251 reduced the Srebf-1 and ChREBP expression and totally abrogated the remnant gene expression of their target lipogenic enzymes. The phosphorylated form of the extracellular signal-regulated kinase (ERK-p), which participates in the CB1-mediated signalling pathway, was markedly present in the PrAT of obese rats. ERK-p was drastically repressed by AM251 indicating that CB1 is actually functional in PrAT of obese animals, though its activation loses the ability to stimulate lipogenesis in PrAT of obese rats. Even so, the remnant expression levels of lipogenic transcription factors found in HCHD-fed rats are still dependent on CB1 activity. Hence, in HCHD-induced obesity, CB1 blockade may help to further potentiate the reduction of lipogenesis in PrAT by means of inducing down-regulation of the ChREBP and Srebf-1 gene expression, and consequently in the expression of lipogenic enzymes.
PB Public Library of Science
YR 2014
FD 2014-02-25
LK http://hdl.handle.net/10668/1976
UL http://hdl.handle.net/10668/1976
LA en
NO Vida M, Rivera P, Gavito AL, Suárez J, Pavón FJ, Arrabal S, et al. CB1 blockade potentiates down-regulation of lipogenic gene expression in perirenal adipose tissue in high carbohydrate diet-induced obesity. PLoS ONE. 2014; 9(2):e90016
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 5, 2025