Low carbohydrate/high fat energy intake increases intramyocellular lipid content in skeletal muscle in rats

The efficiency of “Atkins-style” low-carbohydrate/high fat diets (LC-HFD) in inducing weight loss has been established in both animals and humans. Weight loss during obesity improves insulin sensitivity and reduces the risk of type 2 diabetes. We have previously shown that despite losing body weight, rats fed LC-HFD exhibit severe glucose intolerance. High accumulation of intramyocellular lipids (IMCL) has been associated with decreased insulin sensitivity and glucose tolerance. Therefore, we investigated whether pair-feeding isoenergetic amounts of 2 different LC-HFD affects skeletal muscle IMCL. Male Wistar rats (12-wk old) were isoenergetically pair-fed on chow (CH), “Atkins-style” LC-HFD1, (protein matched to chow, 78.7/19.1/2.2); and ketogenic LC-HFD2 (low protein content, 92.8/5.5/1.7) (% of metabolisable energy, fat/protein/carbohydrate) for 4 weeks. Characterisation of the insulin/glucose phenotype was determined via oral glucose (oGTT) and insulin tolerance tests (ITT). To detect IMCL, gastrocnemius cryosections were stained with Oil-Red-O.

Results: oGTT resulted in a pronounced increase in glucose levels in both LC-HFD groups, together with a higher area under the curve, with no differences between LC-HFD1 and LC-HFD2. The decline in glucose during ITT was delayed in both LC-HFD compared to CH groups (glucose levels after 120 min (mg/dl): CH: 42.7+1.7; LC-HFD1: 75+3.6; LC-HFD2: 93.1+6.5, p < 0.01), with no differences between LC-HFD1 and LC-HFD2 groups. Oil-Red-O muscle stained sections of LC-HFD groups displayed more IMCL compared to chow. Lipid droplets appeared to be larger and recurred more in both LC-HFD groups compared to CH. Taken together, impaired glucose tolerance with LC-HFD is in part due to increased skeletal muscle IMCL content. Furthermore, no significant differences in IMCL content between LC-HFD1 and LC-HFD2 indicate the relative abundance of fat and protein in LC-HFD has no effect on the magnitude of IMCL accumulation.