The Implication of PGC-1α on Fatty Acid Transport across Plasma and Mitochondrial Membranes in the Insulin Sensitive Tissues

Abstract

PGC-1α coactivator plays a decisive role in the maintenance of lipid balance via engagement in numerous metabolic processes (i.e., Krebs cycle, β-oxidation, oxidative phosphorylation and electron transport chain). It constitutes a link between fatty acids import and their complete oxidation or conversion into bioactive fractions through the coordination of both the expression and subcellular relocation of the proteins involved in fatty acid transmembrane movement. Studies on cell lines and/or animal models highlighted the existence of an upregulation of the total and mitochondrial FAT/CD36, FABPpm and FATPs content in skeletal muscle in response to PGC-1α stimulation. On the other hand, the association between PGC-1α level or activity and the fatty acids transport in the heart and adipocytes is still elusive. So far, the effects of PGC-1α on the total and sarcolemmal expression of FAT/CD36, FATP1, and FABPpm in cardiomyocytes have been shown to vary in relation to the type of PPAR that was coactivated. In brown adipose tissue (BAT) PGC-1α knockdown was linked with a decreased level of lipid metabolizing enzymes and fatty acid transporters (FAT/CD36, FABP3), whereas the results obtained for white adipose tissue (WAT) remain contradictory. Furthermore, dysregulation in lipid turnover is often associated with insulin intolerance, which suggests the coactivator's potential role as a therapeutic target.

Dietary supplementation with pioglitazone hydrochloride and chromium methionine manipulates lipid metabolism with related genes to improve the intramuscular fat and fatty acid profile of yellow‐feathered chickens

“…We found that the mRNA abundance of PPAR γ was significantly increased by diets supplemented with PGZ or PGZ plus CrMet. However, no report was found on the influence of CrMet on PPAR γ or other lipid metabolism‐related genes, such as PGC‐1 α . Nonetheless, our data showed stable mRNA abundance of PPAR γ and PGC‐1 α with CrMet supplementation, whereas feeding PGZ plus CrMet enhanced PGC‐1 α significantly, and even the individual PGZ improved the PGC‐1 α mRNA abundance by 93.02%.…”

PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation

“…Furthermore, PGC-1α is involved in lipid distribution and may upregulate FAT/CD36, FABPpm, and FATP1 mRNA and protein expression in mitochondrial fractions. The latter effect was confirmed solely in murine FAT/CD36 and FABP3 cells [ 14 ].…”

Functional analysis finds differences on the muscle transcriptome of pigs fed an n-3 PUFA-enriched diet with or without antioxidant supplementations

“…In literature, it is reported that PPARGC1A may be involved in many biological mechanisms like fatty acid oxidation, glucose utilization, mitochondrial biogenesis, angiogenesis and muscle trophic stimulation [46]. Recent literature [47] demonstrated the role of PPARGC1A in the maintenance of lipid balance via its engagement in numerous metabolic processes related to lipid synthesis and/or lipid utilization ( i . e .…”

“…Krebs cycle, β-oxidation, oxidative phosphorylation and electron transport chain). In particular, in insulin-sensitive tissues such as the skeletal muscle, PPARGC1A is regarded as one of the factors eliciting FA uptake by the cells, controlling their oxidation for energy purposes or esterification for the conversion into bioactive fractions [47]. Other regulatory genes up-regulated in LPE compared to L are PRKACA and PRKAR2A , two genes also involved in glucose and lipid homeostasis and in cell growth [48,49].…”