Effects of Intermittent Fasting or Calorie Restriction on Markers of Lipid Metabolism in Human Skeletal Muscle

Abstract
Context: Impaired lipid metabolism is linked with obesity-associated insulin resistance, which may be reversed by caloric restriction (CR).

Objective: In a secondary analysis of a randomized controlled trial, we compared the effects of intermittent fasting (IF) and CR on markers of lipid metabolism in muscle.

Design: Seventy-six women (body mass index, 25-40 kg/m2) were randomly assigned to 1 of 3 diets for 8 weeks and provided foods at 70% (CR70 and IF70) or 100% (IF100) of energy requirements. IF groups ate breakfast prior to a 24-hour fast on 3 nonconsecutive days per week. On nonfasting days, IF70 ate at 100% and IF100 ate at 145% of energy requirements to achieve the prescribed target. Weight, body composition, insulin sensitivity by clamp, nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and markers of lipid metabolism and oxidative stress in muscle by quantitative polymerase chain reaction were measured at baseline and week 8 following a 12-hour overnight fast (all groups) and 24-hour fast (IF groups).

Results: IF70 resulted in greater weight and fat loss and reduced NEFAs vs CR70 and IF100 after an overnight fast. IF70 and IF100 induced a greater reduction only in mRNA levels of antioxidant enzymes glutathione peroxidase 1 (GPX1), superoxide dismutase 1, soluble (SOD1), and SOD2 vs CR70. Fasting for 24 hours increased NEFAs and BHB in IF groups, but impaired insulin sensitivity and increased PLIN5 mRNA levels.

Conclusions: In comparison to CR, IF did not increase markers of lipid metabolism in muscle, but reduced expression of antioxidant enzymes. However, fasting-induced insulin resistance was detected, alongside increased PLIN5 expression, potentially reflecting transient lipid storage.

Keywords: calorie restriction; intermittent fasting; lipid metabolism; mitochondria; muscle; obesity.