Background: Acute prolonged fasting (48-72 hours) induces insulin resistance and increases lipid accumulation in skeletal muscle in humans1-3. Whether this occurs in intermittent 24-hour fasting (IF) is unclear. This study compared the effects of 8-weeks of dietary restriction (DR) versus IF on markers of lipid metabolism in skeletal muscle in women with obesity.
Methods: Women (N=75, 50.3±1.0y, BMI 32.4±0.5 kg/m2) were randomised to 1 of 3 groups for 8 weeks, and provided with foods at 70% (IF70 and DR70), or 100% (IF100) of energy requirements. DR70 participants consumed food daily, whereas IF participants ate breakfast, prior to initiating a 24-hour fast, for 3 non-consecutive days/week. Fasting serum, insulin sensitivity by the hyperinsulinaemic‐euglycaemic clamp, respiratory quotient (RQ) by indirect calorimetry, and quadriceps muscle biopsies were obtained at baseline and 8 weeks, after a 12-hour overnight fast (N=12-16/group), and 24-hour fast (IF groups). mRNA levels of genes involved in lipid uptake (CD36), lipid synthesis (PLIN5 and DGAT1) and lipid oxidation (PPARα and CPT1) in muscle were assessed by qPCR.
Results: Significantly reductions in weight and serum total cholesterol were observed in IF70 vs. DR70 and IF100 (P<0.05). A 24-hour fast increased lipid oxidation (reduced RQ) and serum non-esterified fatty acids and beta-hydroxybutyrate in IF groups, but transiently induced insulin resistance on the fasting day in IFs vs. DR70 (P<0.05). There was no increase in mRNA levels of genes involved in lipid oxidation. PPARα and CD36 mRNA levels were reduced in IF100 vs. DR70 (P<0.05). The 24-hour fast increased DGAT1 mRNA levels in IFs vs. DR70 (P<0.05), and tended to increase PLIN5 mRNA levels in IF70 vs. DR70 (P=0.08).
Conclusions: Intermittent fasting transiently increased insulin resistance and markers of lipid synthesis, but not markers of lipid oxidation in muscle, despite increasing whole body lipid oxidation. The effects of IF on lipid deposition within skeletal muscle requires investigation.