Kunz 2019 Am J Physiol Endocrinol Metab
|Kunz HE, Dasari S, Lanza IR (2019) EPA and DHA elicit distinct transcriptional responses to high-fat feeding in skeletal muscle and liver. Am J Physiol Endocrinol Metab [Epub ahead of print].|
Abstract: Omega-3 fatty acids (n-3 PUFAs) exert numerous beneficial biological effects and attenuate diet-induced insulin resistance in rodent models. In the present study, the independent, tissue-specific effects of two nutritionally-relevant n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were characterized in the context of a high fat diet (HFD). EPA and DHA supplementation (3.2% of total fat), in 6-month-old male, C57BL/6 mice fed HFD (60% fat) partially mitigated reductions in insulin sensitivity. At 5 weeks, the area above the curve below baseline glucose following an intraperitoneal insulin tolerance test was 54.5% lower in HFD than control, while HFD+EPA and HFD+DHA showed 27.6% and 17.1% reductions, respectively. At 10 weeks, HFD increased mitochondrial oxidative capacity supported by lipid and carbohydrate-based substrates in both liver and skeletal muscle (p<0.05), with little effect of EPA or DHA supplementation. Whole-genome transcriptomic analyses revealed HFD-induced transcriptional changes indicative of inflammation and fibrosis in both liver and muscle. Gene set enrichment analyses indicated a downregulation of transcripts associated with extracellular matrix in muscle (family-wise error rate p<0.01) and liver (p=0.04) and in transcripts associated with inflammation in muscle (p=0.03) in HFD+DHA compared to HFD alone. In contrast, EPA appeared to potentiate some pro-inflammatory effects of the HFD. In the skeletal muscle, DHA increased the expression of stress-responsive genes, while EPA upregulated the expression of transcripts related to cell cycle. Therefore, while both EPA and DHA supplementation during HFD partially preserve insulin signaling they modulate distinct processes, highlighting their unique biological effects in the context of obesity.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Organism: Mouse Tissue;cell: Skeletal muscle, Liver Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS Pathway: F, N, S, NS, ROX HRR: Oxygraph-2k