The Effect of Colonic SCFA on Energy Homeostasis

Abstract

Fiber consumption is negatively associated with body weight in humans and fiber supplementation improves energy homeostasis, due in part to the gut microbiome. Bacteria in the distal intestine ferment fiber into short chain fatty acids (SCFAs). We recently demonstrated that obesity is associated with decreased postprandial levels of distal intestine SCFAs; however, the impact of endogenous SCFAs on energy homeostasis is still unknown. Exogenous SCFAs improve energy homeostasis, an effect partly mediated by free fatty acid receptors (FFAR2 and FFAR3) located on enteroendocrine cells and neurons. However, studies outlining the suppressive effects of exogenous SCFAs on food intake often target the small intestine or circulation rather than replicating an increase in endogenous production in the distal intestine. To address this, we equipped male Sprague Dawley rats with proximal colon catheters and, following recovery, administered 200mM acetate, butyrate, propionate or saline at a rate of 0.15mL/min for 15min after a 12hr overnight fast. Rats were then returned to metabolic cages for 24hrs to assess food intake, energy expenditure, RER, and activity. SCFA infusions were bracketed by saline infusions and given every other day. All three SCFAs significantly suppressed food intake 1 and 12hrs post-infusion compared to saline, with no effect on energy expenditure (n=6-8). None of the acute SCFA administrations significantly impacted food intake, energy expenditure, or RER 24hrs post-infusion. To address the ability of SCFA administration to regulate energy homeostasis over a longer period of time, we infused acetate, propionate, butyrate or saline daily in a SCFA or control group. We found that only butyrate reduced cumulative intake compared to control and there were no other changes between SCFA and control treatments. Taken together, these data show that acute exogenous administration of acetate, propionate, or butyrate to the distal intestine suppresses food intake up to 12hrs post-infusion, potentially through similar mechanisms, but this effect is not replicated in a chronic daily infusion study for acetate or propionate.