Obesity has been linked to changes in plasma and faecal levels of short-chain fatty acids, including acetate, but whether these changes cause weight gain is unclear. Perry et al. found that rats receiving a high-fat diet developed an increase in whole-body acetate levels that was attributable to increased acetate production by the gut microbiota. The rise in acetate levels increased parasympathetic nervous system activity and glucose-stimulated insulin secretion. Interestingly, chronic intragastric infusion of acetate into rats receiving a normal diet led to insulin resistance and marked weight gain. Thus, microbiota-produced acetate might promote obesity.