Ketone body supplementation into a standard high-carbohydrate diet reduces fecundity, delays larval development, and may induce autophagy in Drosophila melanogaster

Abstract

Fasting (typically intermittent; IF), caloric restriction (CR), and the increasingly-popular high-fat, low-carbohydrate ketogenic diet (KD) count among many starvation-mimicking dietary regimens known to exert diverse effects on cellular and whole-organism behavioral, developmental, and physiological parameters. These effects include lowering neuronal excitability, inducing the cellular-component-recycling process of autophagy, altering reproductive outcomes (especially in pathological cases), and extending lifespan. These challenging diet regimens can produce elevated levels of circulating ketone bodies (KBs), which themselves are known to exert numerous potentially-beneficial genetic and signaling effects. We applied KBs as a supplement (KBS) directly into a standard high-carbohydrate (SHC) Drosophila culture-media diet for wild-type flies. We found that KBS reduced female fecundity (measured as egg laying) and significantly delayed larval developmental timelines, possibly via induction of elevated autophagy, of which we detected some evidence in the fat-body organs of third-instar larvae. Our findings suggest that dietary KBS may elevate autophagic processes in the manner of starvation-like dietary regimens. Further, through autophagy-related biochemical and cellular processes, KBS may induce biological responses that may thus help provide health benefits similar to those associated with IF, CR, and the KD itself.