RT Journal Article
T1 Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white adipose tissue in rat.
A1 Suárez, Juan
A1 Rivera, Patricia
A1 Arrabal, Sergio
A1 Crespillo, Ana
A1 Serrano, Antonia
A1 Baixeras, Elena
A1 Pavón, Francisco J
A1 Cifuentes, Manuel
A1 Nogueiras, Rubén
A1 Ballesteros, Joan
A1 Dieguez, Carlos
A1 Rodríguez de Fonseca, Fernando
K1 Peroxisome proliferator-activated receptor alpha
K1 β3-adrenergic receptor
K1 Thermogenesis
K1 β-oxidation
K1 Adipocyte
K1 PPAR alfa
K1 Termogénesis
K1 Ratas
K1 Regulación del apetito
K1 Peso corporal
AB β-adrenergic receptor activation promotes brown adipose tissue (BAT) β-oxidation and thermogenesis by burning fatty acids during uncoupling respiration. Oleoylethanolamide (OEA) can inhibit feeding and stimulate lipolysis by activating peroxisome proliferator-activating receptor-α (PPARα) in white adipose tissue (WAT). Here we explore whether PPARα activation potentiates the effect of β3-adrenergic stimulation on energy balance mediated by the respective agonists OEA and CL316243. The effect of this pharmacological association on feeding, thermogenesis, β-oxidation, and lipid and cholesterol metabolism in epididymal (e)WAT was monitored. CL316243 (1 mg/kg) and OEA (5 mg/kg) co-administration over 6 days enhanced the reduction of both food intake and body weight gain, increased the energy expenditure and reduced the respiratory quotient (VCO2/VO2). This negative energy balance agreed with decreased fat mass and increased BAT weight and temperature, as well as with lowered plasma levels of triglycerides, cholesterol, nonessential fatty acids (NEFAs), and the adipokines leptin and TNF-α. Regarding eWAT, CL316243 and OEA treatment elevated levels of the thermogenic factors PPARα and UCP1, reduced p38-MAPK phosphorylation, and promoted brown-like features in the white adipocytes: the mitochondrial (Cox4i1, Cox4i2) and BAT (Fgf21, Prdm16) genes were overexpressed in eWAT. The enhancement of the fatty-acid β-oxidation factors Cpt1b and Acox1 in eWAT was accompanied by an upregulation of de novo lipogenesis and reduced expression of the unsaturated-fatty-acid-synthesis enzyme gene, Scd1. We propose that the combination of β-adrenergic and PPARα receptor agonists promotes therapeutic adipocyte remodelling in eWAT, and therefore has a potential clinical utility in the treatment of obesity.
PB Company of Biologists
SN 1754-8403
YR 2014
FD 2014-01-07
LK http://hdl.handle.net/10668/1609
UL http://hdl.handle.net/10668/1609
LA en
NO Suárez J, Rivera P, Arrabal S, Crespillo A, Serrano A, Baixeras E, et al. Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white adipose tissue in rat. Dis Model Mech. 2014; 7(1):129-41
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 11, 2025