👤 Sarthak Matravadia

Evidence shows that proteins secreted from skeletal muscle influence a broad range of metabolic signaling pathways. We previously reported that essential polyunsaturated fatty acids (PUFA) improved whole-body glucose homeostasis in obese Zucker rats; however, the mechanisms underlying these benefits remain enigmatic. While PUFA and obesity influence skeletal muscle function, their effects on the secretome are unknown. The aim of this work was to determine if improvements in whole-body glucose homeostasis in obese Zucker rats fed diets supplemented with either linoleic acid (LA) or alpha-linolenic acid (ALA) for 12 wk are related to changes in the skeletal muscle secretome. Secreted proteins were identified with a predictive bioinformatic analysis of microarray gene expression from red tibialis anterior skeletal muscle. Approximately 130 genes were differentially expressed (false discovery rate = 0.05) in obese rats compared with lean controls. The expression of 15 genes encoding secreted proteins was differentially regulated in obese controls, obese LA-supplemented, and obese ALA-supplemented rats compared with lean controls. Five secreted proteins ( Col3a1, Col15a1, Pdgfd, Lyz2, and Angptl4) were differentially regulated by LA and ALA. Most notably, ALA supplementation reduced Angptl4 gene expression compared with obese control and obese-LA supplemented rats and reduced circulating ANGPTL4 serum concentrations. ALA also influenced Angptl4 gene expression and ANGPTL4 secretion from differentiated rat L6 myotubes. Altogether, the present data indicate that obesity has a greater global impact on skeletal muscle gene expression than either essential PUFA; however, LA and ALA may exert their metabolic benefits in part by regulating the skeletal muscle secretome. Show less

Polyunsaturated fatty acids (PUFAs) regulate fatty acid desaturase (FADS1, FADS2) expression in the liver; however, it is unknown whether PUFAs regulate FADS in adipocytes. This is important to study considering reports that link altered desaturase activity with adipose tissue PUFA profiles, body weight, and whole-body glucose homeostasis. Therefore, the present study aimed to determine the direct effects of PUFAs on FADS expression in differentiated 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were treated with either α-linolenic (ALA), linoleic (LA), eicosapentaenoic (EPA), or arachidonic acid (AA). Gene expression, protein abundance, and cellular PUFA content were analyzed by real-time RT-PCR, Western blotting, and gas chromatography, respectively. Fads1 and Fads2 gene expression was reduced by EPA and AA, but not ALA or LA. Reductions in gene expression were reflected in FADS2 protein levels, but not FADS1. Treating cells with ALA and LA led to significant increases in the cellular content of downstream PUFAs. Neither ALA nor EPA changed docosahexaenoic acid content. Differentiated 3T3-L1 adipocytes have a functional FADS pathway that can be regulated by PUFA. Therefore, this common adipocyte model is suitable to study dietary regulation of the FADS pathway. Show less