The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism

Abstract

Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo ¹¹C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through ¹³C high-resolution magic-angle-spinning that ¹³C acetate from fermentation of ¹³C-labelled carbohydrate in the colon increases hypothalamic ¹³C acetate above baseline levels. Hypothalamic ¹³C acetate regionally increases the ¹³C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic ¹³C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation.

Abstract

The consumption of fermentable carbohydrates, or fibre, is associated with weight loss. Here the authors show that the metabolite acetate, created by fermentation of fibre in the mouse colon, is taken up into the brain where it induces appetite-suppressing neuronal activity in the hypothalamus.