Philp, L.Heilbronn, L.Janovska, A.Wittert, G.Alemany, M.2015-03-262015-03-262015PLoS ONE, 2015; 10(2):e0117494-1-e0117494-191932-62031932-6203http://hdl.handle.net/2440/90177High saturated fat (HF-S) diets increase intramyocellular lipid, an effect ameliorated by omega-3 fatty acids in vitro and in vivo, though little is known about sex- and muscle fiber type-specific effects. We compared effects of standard chow, HF-S, and 7.5% HF-S replaced with fish oil (HF-FO) diets on the metabolic profile and lipid metabolism gene and protein content in red (soleus) and white (extensor digitorum longus) muscles of male and female C57BL/6 mice (n = 9-12/group). Weight gain was similar in HF-S- and HF-FO-fed groups. HF-S feeding increased mesenteric fat mass and lipid marker, Oil Red O, in red and mixed muscle; HF-FO increased interscapular brown fat mass. Compared to chow, HF-S and HF-FO increased expression of genes regulating triacylglycerol synthesis and fatty acid transport, HF-S suppressed genes and proteins regulating fatty acid oxidation, whereas HF-FO increased oxidative genes, proteins and enzymes and lipolytic gene content, whilst suppressing lipogenic genes. In comparison to HF-S, HF-FO further increased fat transporters, markers of fatty acid oxidation and mitochondrial content, and reduced lipogenic genes. No diet-by-sex interactions were observed. Neither diet influenced fiber type composition. However, some interactions between muscle type and diet were observed. HF-S induced changes in triacylglycerol synthesis and lipogenic genes in red, but not white, muscle, and mitochondrial biogenesis and oxidative genes were suppressed by HF-S and increased by HF-FO in red muscle only. In conclusion, HF-S feeding promotes lipid storage in red muscle, an effect abrogated by the fish oil, which increases mediators of lipolysis, oxidation and thermogenesis while inhibiting lipogenic genes. Greater storage and synthesis, and lower oxidative genes in red, but not white, muscle likely contribute to lipid accretion encountered in red muscle. Despite several gender-dimorphic genes, both sexes exhibited a similar HF-S-induced metabolic and gene expression profile; likewise fish oil was similarly protective in both sexes.en© 2015 Philp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [http://creativecommons.org/licenses/by/4.0/], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Muscle, SkeletalMitochondriaAnimalsMice, Inbred C57BLMiceCarbon-Carbon Double Bond IsomerasesRacemases and EpimerasesEnoyl-CoA Hydratase3-Hydroxyacyl CoA DehydrogenasesAcetyl-CoA C-AcyltransferaseTriglyceridesFish OilsRNA, MessengerOxidative PhosphorylationFemaleMaleLipogenesisLipid MetabolismFatty Acid Transport ProteinsAdipose Tissue, BrownAdipose Tissue, WhiteDiet, High-FatJournal article003002162710.1371/journal.pone.01174940003494449001642-s2.0-84922575713171225Heilbronn, L. [0000-0003-2106-7303]Wittert, G. [0000-0001-6818-6065]