Impaired glucose tolerance with low-carb/high fat diets occurs independent of increased fat mass in rats

Using hyperinsulinemic-euglycemic clamps we previously showed that iso-energetic consumption of low-carbohydrate/high fat diets (LCHFD) leads to impaired glucose tolerance and insulin resistance in rats. Rats pair-fed with LCHFD also displayed higher visceral fat mass and circulating leptin. We now investigated if visceral fat accumulation is responsible for impaired glucose tolerance and clamped the fat mass of LCHF groups to controls by restricting energetic intake. Rats on a standard rodent chow (CH) were compared to rats on one of two different LCHFD (% of metabolizable energy, fat/protein/CHO: LCHF-1 (78.7/19.1/2.2), LCHF-2 (92.8/5.5/1.7) and CH (16.7/19./64.3)). After 3 weeks of feeding the respective diets (either pair-fed or only 80% of pair-fed groups), oral glucose tolerance tests (oGTT) were performed (n = 5/diet group). After 4 weeks, rats were fasted (6h) and sacrificed.

Results: As expected, rats pair-fed with both LCHFD had significantly higher fat mass compared to CH. Reduction of LCHFD intake to 80% clamped the visceral fat mass between LCHFD and CH groups. Fasting glucose and insulin levels were lower in rats pair-fed the LCHFD vs. CH (p < 0.05), and even lower in rats fed 80% of LC-HFD. During oGTT, rats pair-fed both LCHFD showed impaired glucose tolerance when compared to CH. Restriction of LCHFD intake to 80% improved glucose tolerance during oGTT compared to pair-fed rats. However, glucose tolerance was still worse than in rats on CH (AUC; CH: 12986 ± 801; LC-HF-1(80%): 15662 ± 1111; LC-HF-2(80%): 23809 ± 1485; CH vs. LC-HF-1(80%): p = 0.087; CH vs. LC-HF-2(80%): p < 0.001). Insulin secretion during oGTT tended to be higher in 80% LCHFD vs. unrestricted groups (n.s). Although glucose tolerance in the 80% restricted LCHFD rats was somewhat better, we conclude that the impaired glucose tolerance with LCHFD is only in part related to the accumulation of visceral fat. Apparently the composition of the LC-HFD per se has a negative impact on glucose tolerance.