Writing in The Journal of Nutritional Biochemistry, the French research team investigated the effect of docosahexaenoic acid (DHA) against insulin resistance, lipotoxicity (the accumulation of lipid intermediates) and inflammation in skeletal muscle at doses compatible with nutritional supplementation.
Findings from the in vitro and in vivo studies suggested that DHA used at physiological doses can play a role in the regulation of muscle lipid and glucose metabolisms by preventing lipotoxicity and inflammation.
“Although further studies should be performed in skeletal muscle from supplemented humans, our results strongly suggested that supplementation with DHA can be an effective healthy strategy against muscle metabolic disorders,” said the research team – led by senior author Dr. Béatrice Morio of INRA, France.
“Beneficial effects were observed at physiological or supplemental doses both in vitro and in vivo in contexts favouring the occurrence of lipotoxicity and inflammation,” said the team adding that it appears that DHA improves the palmitate-induced impairment of mitochondrial fatty acid oxidation and, and also reduces palmitate-induced lipotoxicity and inflammation.
The INRA team investigated the impact of DHA on inflammation, lipotoxicity and fatty acid oxidative capacity in C2C12 myotubes (a mouse cell line that serves as a model for skeletal muscle) exposed to a high dose of palmitic acid, and in muscle from living animals supplemented with three nutritional doses of DHA - in order to support their use as preventive nutritional strategies.
DHA at 30 μM was found to prevent insulin resistance in C2C12 myotubes exposed to palmitate (500 μM) by decreasing activation of an enzyme known as protein kinase C theta (PKC-theta) and restoring cellular acylcarnitine profile, insulin dependent-AKT phosphorylation and glucose uptake.
Furthermore, DHA protected C2C12 myotubes from palmitate- or lipopolysaccharide-induced increases in inflammatory markers including IL6 and TNF-alpha, “probably through the inhibition of p38 MAP kinase and JNK.”
“An in vivo study was also performed in mice fed with a high cholesterol-high sucrose diet and receiving nutritional doses of DHA,” added the team. “This intervention allowed a significant decrease of plasma triglycerides and prevented the progression of atherosclerosis.”
“We found here that DHA significantly reduced plasma glucose and improved insulin-induced Akt activation in skeletal muscle from these animals,” said the authors.
Source: The Journal of Nutritional Biochemistry
Published online ahead of print, doi: 10.1016/j.jnutbio.2015.04.003
“DHA at nutritional doses restores insulin sensitivity in skeletal muscle by preventing lipotoxicity and inflammation”
Authors: F. Capel, et al