Anti-PPARA Monoclonal antibody, clone 4C7/QQBS

The small heterodimer partner (SHP) regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR) gamma expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing not only heart structure and function but also lipid metabolism and related gene expression in a SHP deletion animal model. Transcriptional profiling with a microarray revealed that genes participating in cell growth, cytokine signalling, phospholipid metabolism, and extracellular matrix are up-regulated in the myocardia of SHP knockout (KO) mice compared to those of wild-type (WT) mice (nominal p value < 0.05). Consistent with these gene expression changes, the left ventricular masses of SHP KO mice were significantly higher than WT mice (76.8 +/- 20.5 mg vs. 52.8 +/- 6.8 mg, P = 0.0093). After 12 weeks of high fat diet (HFD), SHP KO mice gained less weight and exhibited less elevation in serum-free fatty acid and less ectopic lipid accumulation in the myocardium than WT mice. According to microarray analysis, genes regulated by PPAR gamma 1 and PPAR alpha were down-regulated in myocardia of SHP KO mice compared to their expression in WT mice after HFD, suggesting that the reduction in lipid accumulation in the myocardium resulted from a decrease in lipogenesis regulated by PPAR gamma. We confirmed the reduced expression of PPAR gamma 1 and PPARa target genes such as CD36, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase by SHP KO after HFD.

Lipids play important roles in growth, reproduction, locomotion, and migration of fish. Municipal effluents, which are complex mixtures of biological and chemical compounds including flame retardants, have been shown to alter lipid metabletabolism in environmentally and experimentally exposed fish. Down-regulation of several genes coding for fatty acid metabolism enzymes has previously been reported in male northern pike (Esox lucius) collected in the St. Lawrence River (QC, Canada) downstream of a major primary wastewater treatment plant (WWTP) point of discharge. The main objective of this study was to investigate the effects of exposure to the Montreal's WWTP effluent on the lipidomic profile (i.e., fatty acids, acylcarnitines, and phospholipids) as well as the transcription of genes related to lipid metabolism in the liver of northern pike collected upstream and downstream of this WWTP effluent. Halogenated flame retardant concentrations were also determined in pike liver and used as markers of exposure to this effluent. Greater concentrations of saturated and monounsaturated lysophosphatidylcholines (LPCs) and lower concentrations of polyunsaturated LPCs were determined in the liver of pike collected downstream of the WWTP compared to those collected upstream. Lower mRNA levels of peroxisome proliferator-activated receptor alpha (ppara), a major regulator of lipid metabolism, were also measured in pike exposed to Montreal's WWTP effluent. In addition, the relative contributions (%) of LPC 18:2 and LPC14:0, compounds used as markers of obesity and inflammation, were significantly correlated with halogenated flame retardant concentrations and fish girth. Results of the present study suggest that chronic environmental exposure to a primary WWTP effluent can modulate the transcription of genes related to lipid metabolism, and hence affect the hepatic phospholipid composition of pike from the St. Lawrence River.