Profound sex-specific differences of metabolic hormone and adipose tissue dynamics induced by moderate low-carbohydrate and ketogenic diet

Low-carbohydrates diets are increasingly used to treat obesity and metabolic disorders. A very low-carbohydrate, ketogenic diet is hard to follow and is linked to severe side effects. Therefore, a less restrictive unsaturated fat-based low-carbohydrate diet seems a promising alternative. Since neither sex differences, nor their effect on specific adipose tissue compartments have been investigated thoroughly in these diets, we aimed to analyze their dynamics and metabolic factors in mice. We found a significant sexual dimorphism with decreased body weight and subcutaneous fat only in males on ketogenic diet, while diminished insulin, elevated ghrelin and FGF-21 were present with a differential time course in both sexes. The non-ketogenic low-carbohydrate diet increased body weight and visceral fat in females, but induced leptin elevation in males. Both diets induced transient TNFɑ increase only in males and had no impact on behavior. Altogether, these results reveal complex sex-dependent effect of dietary interventions, indicating unexpectedly females as more prone to unfavorable metabolic effects of low-carbohydrate diets.