Docosahexaenoic acid regulates adipogenic genes in myoblasts via porcine peroxisome proliferator-activated receptor γ1

Abstract

The nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) triggers adipocyte differentiation by regulating lipogenic genes. A ligand for PPARgamma is necessary to activate PPARgamma function. Fatty acids are potential ligands for PPARgamma activation. The current experiment was designed to determine the potential for individual fatty acids to activate porcine PPARgamma ectopically expressed in myoblasts. The expression of adipocyte fatty acid binding protein (aP2) and adiponectin in myoblasts stably expressing porcine PPARgamma was increased when docosahexaenoic acid (DHA) was added to the adipogenic medium. The response was positively related to DHA concentration and suggests that DHA may bind to and activate porcine PPARgamma, leading to increased expression of aP2 and adiponectin. The conditioned media collected from myoblasts expressing PPARgamma between d 3 and 6 or between d 6 and 9, but not DHA itself, activated the aP2 gene promoter-driven luciferase activity. These results suggest that a metabolite of DHA is the ligand binding to and activating porcine PPARgamma. The metabolite and pathway for its production are currently unknown.

The function of porcine PPARγ and dietary fish oil effect on the expression of lipid and glucose metabolism related genes

“…Dietary fish oil prevents insulin resistance in high-fat-fed rats [23] by regulating adiponectin secretion [9]. Studies in vitro suggest that DHA has high affinity for human [5], monkey [7] and porcine PPARγ [12]. In the current study, we found that plasma glucose concentration was not affected by fish oil feeding in wild-type mice but was significantly decreased in fish oil-fed transgenic mice expressing high levels of PPARγ in skeletal muscle.…”

“…The PUFA, DHA or its metabolites are able to activate porcine PPARγ [12]. Because muscle is the major organ to metabolize glucose and one of the important organs to utilize lipids, we generated muscle-specific expression of porcine PPARγ in transgenic mice to study the function of PPARγ.…”

Docosahexaenoic acid suppresses the expression of FoxO and its target genes

“…Therefore, the inhibitory effect of DHA on FoxO1 function observed here may be explained by the competition between FoxO1 and PPARγ for target promoter. It may also due to the fact that DHA is a potent ligand for porcine PPARγ activation [43,44]. However, the underlying mechanism awaits further investigation.…”

Eicosapentaenoic and docosahexaenoic acids as inflammation-modulating and lipid homeostasis influencing nutraceuticals: A review

“…Moreover, activation of PPAR and SREBP and their target genes by DHA (EPA) in the model organisms increases with increasing DHA concentration in the range of nearly one order (Yu et al, 2008), and the extent of the effect depends also on the length of the time interval of fatty acid application: in pigs, extent of the expression of genes positively influencing adipogenesis (PPARd, PPARc, FABP, lipoprotein lipase) increased linearly with increasing fattening interval using a diet containing a-linolenic acid (Luo et al, 2009). In human subjects, plasma DHA concentration equilibrated after one month of supplementation, near maximal plasma response was reached with DHA daily doses of 2 g (Arterburn, Hall, & Oken, 2006).…”