Butyrate and Propionate Protect against Diet-Induced Obesity and Regulate Gut Hormones via Free Fatty Acid Receptor 3-Independent Mechanisms
By Hua V. Lin, A. Frassetto, Edward J. Kowalik Jr, A. Nawrocki, Mofei Lu, Jennifer R. Kosinski, J. Hubert, Daphne Szeto, Xiaorui Yao, Gail Forrest and 1 more. PLoS ONE, 2012
1,341 citations recorded by the source corpus.
Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are metabolites formed by gut microbiota from complex dietary carbohydrates. Butyrate and acetate were reported to protect against diet-induced obesity without causing hypophagia, while propionate was shown to reduce food intake. However, the underlying mechanisms for these effects are unclear. It was suggested that SCFAs may regulate gut hormones via their endogenous receptors Free fatty acid receptors 2 (FFAR2) and 3 (FFAR3), but direct evidence is lacking. We examined the effects of SCFA administration in mice, and show that butyrate, propionate, and acetate all protected against diet-induced obesity and insulin resistance. Butyrate and propionate, but not acetate, induce gut hormones and reduce food intake. As FFAR3 is the common receptor activated by butyrate and propionate, we examined these effects in FFAR3-deficient mice. The effects of butyrate and propionate on body weight and food intake are independent of FFAR3. In addition, FFAR3 plays a minor role in butyrate stimulation of Glucagon-like peptide-1, and is not required for butyrate- and propionate-dependent induction of Glucose-dependent insulinotropic peptide. Finally, FFAR3-deficient mice show normal body weight and glucose homeostasis. Stimulation of gut hormones and food intake inhibition by butyrate and propionate may represent a novel mechanism by which gut microbiota regulates host metabolism. These effects are largely intact in FFAR3-deficient mice, indicating additional mediators are required for these beneficial effects.
Subfields: Endocrine and Autonomic Systems, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/17d96108335064058bd1949bf86c2d3b5523bf27
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Citations in the corpus
- The Impact of Diet and Lifestyle on Gut Microbiota and Human Health (2014, background): “However, other data suggests the shifts in microbial populations are driven primarily by the high fat obesogenic diets [50,51].”
- The human gut microbiota: Metabolism and perspective in obesity (2018, background): “A significant amount of acetate enters the systemic circulation and reaches the peripheral tissues, while the propionate is mainly used in liver, and the butyrate is used in intestinal epithelium as an energy source.(37) The total and relative concentrations of SCFA depend on the fermentation site, ”
- Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers (2018, background): “It may be protective against several diseases, including colorectal cancer (5), inflammatory bowel disease (6), graft-versus-host disease (7), diabetes (8), and obesity (8, 9).”
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- Short chain fatty acids in human gut and metabolic health. (2020, positive): “Lin et al. reported a significant increase in food intake in GPR41 KO mice fed a high fat diet (Lin et al. , 2012).”
- Butyrate: A Double-Edged Sword for Health? (2018, background): “The stimulation of gut hormones and inhibition of food intake by butyrate may represent a novel mechanism by which the gut microbiota regulates host metabolism (92).”