Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods

Background: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. Objectives: We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. Design: In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level–dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). Results: Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. Conclusion: Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438

The effect of increased colonic propionate production on appetite regulation and energy homeostasis in humans

Propionate is a short chain fatty acid produced in the colon via fermentation of undigested foods. Elegant in vitro and in vivo studies have shown that increased production of propionate in the gut can reduce body weight and energy intake, and improve glucose homeostasis. These positive effects have been attributed to increased levels of the gut hormones, PYY and GLP-1, increased energy expenditure and improved beta-cell function. Furthermore, bariatric surgery increases levels of colonic propionate and this likely contributes to the huge weight loss seen with this treatment. Additionally, other short chain fatty acids and the consumption of fermentable carbohydrates to increase levels of short chain fatty acids can delay gastric emptying and affect the central regulation of appetite. Taken together, these findings suggest propionate could have several beneficial health effects in humans. Inulin-propionate ester was developed to deliver propionate to the colon. Effects of acute delivery of propionate to the colon with a single dose of inulin-propionate ester was investigated in healthy human volunteers on energy intake, subjective ratings of appetite and satiety and plasma glucose and insulin levels. Potential mechanisms for any effects were explored by assessing plasma levels of PYY and GLP-1, gastric emptying using 13C-octanoic acid, energy expenditure using indirect calorimetry, and central effects using fMRI. In addition, encapsulated sodium propionate was used to assess delivery to the small intestine on appetite and glucose and insulin levels. Acutely increasing colonic levels of propionate significantly reduced energy intake, increased satiety, increased levels of PYY and GLP-1, and reduced anticipatory food behaviour in humans. No effects were observed on gastric emptying, plasma levels of glucose and insulin and energy expenditure. In addition, delivery of propionate to the small intestine did not affect appetite or plasma levels of glucose and insulin. Colonic propionate significantly reduced energy intake and reduced appetite likely through increasing levels of GLP-1 and PYY and reducing anticipatory food behaviour. In addition, propionate does not affect appetite or glucose and insulin levels via the small intestine. As obesity is a growing epidemic, it is likely that interventions that increase colonic propionate levels could prevent weight gain or drive weight loss by regulating energy homeostasis.Open Acces

Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments

Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments