Abstract
Fasting promotes triglyceride (TG) accumulation in lean tissues of some animals, but the effect in humans is unknown. Additionally, fasting lipolysis is sexually dimorphic in humans, suggesting that lean tissue TG accumulation and metabolism may differ between women and men. This study investigated lean tissue TG content and metabolism in women and men during extended fasting. Liver and muscle TG content were measured by magnetic resonance spectroscopy during a 48-h fast in healthy men and women. Whole-body and hepatic carbohydrate, lipid, and energy metabolism were also evaluated using biochemical, calorimetric, and stable isotope tracer techniques. As expected, postabsorptive plasma fatty acids (FAs) were higher in women than in men but increased more rapidly in men with the onset of early starvation. Concurrently, sexual dimorphism was apparent in lean tissue TG accumulation during the fast, occurring in livers of men but in muscles of women. Despite differences in lean tissue TG distribution, men and women had identical fasting responses in whole-body and hepatic glucose and oxidative metabolism. In conclusion, TG accumulated in livers of men but in muscles of women during extended fasting. This sexual dimorphism was related to differential fasting plasma FA concentrations but not to whole body or hepatic utilization of this substrate.
Highlights
We examined the effect of fasting on lipid and glucose metabolism in healthy women (n = 9) and men (n = 9), examining for the first time physiologic changes that occur in hepatic TG content
The classic metabolic effects of fasting began after 24 h and were marked by a rapid rise in plasma-free fatty acids (FAs) and ketones with a concomitant decrease in plasma glucose, insulin, and leptin
Consistent with prior reports [16], significant differences in plasma-free FA concentration were apparent between the sexes (Fig. 1A, B), with women having higher free FAs in the postabsorptive period and men having a 4-fold greater rate of increase in concentration over a 48-h fast
Summary
Participants Healthy individuals were recruited for study at the University of Texas Southwestern Medical Center. All of the women studied were premenopausal, and two were taking oral contraceptives. The protocol and consent form were approved by the UTSW Institutional Review Board, and all participants provided written informed consent before enrollment
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