Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms?

Abstract

In recent years, there has been a renewed interest in the role of dietary fibre in obesity management. Much of this interest stems from animal and human studies which suggest that an increased intake of fermentable fibre can suppress appetite and improve weight management. A growing number of reports have demonstrated that the principal products of colonic fermentation of dietary fibre, SCFA, contribute to energy homeostasis via effects on multiple cellular metabolic pathways and receptor-mediated mechanisms. In particular, over the past decade it has been identified that a widespread receptor system exists for SCFA. These G-protein-coupled receptors, free fatty acid receptor (FFAR) 2 and FFAR3 are expressed in numerous tissue sites, including the gut epithelium and adipose tissue. Investigations using FFAR2-or FFAR3-deficient animal models suggest that SCFAmediated stimulation of these receptors enhances the release of the anorectic hormones peptide tyrosine tyrosine and glucagon-like peptide-1 from colonic L cells and leptin from adipocytes. In addition, the SCFA acetate has recently been shown to have a direct role in central appetite regulation. Furthermore, the SCFA propionate is a known precursor for hepatic glucose production, which has been reported to suppress feeding behaviour in ruminant studies through the stimulation of hepatic vagal afferents. The present review therefore proposes that an elevated colonic production of SCFA could stimulate numerous hormonal and neural signals at different organ and tissue sites that would cumulatively suppress short-term appetite and energy intake.Colonic fermentation: SCFA: Appetite: Gut hormone: Obesity Recent longitudinal studies highlight that adults increase body weight gradually through middle age, with an average annual weight gain of approximately 0·5 kg (1,2) . This accumulation of body weight has resulted in an increased prevalence of obesity and its associated co-morbidities, as obesity incidence rates are now above 20 % in most Western countries and represent a major public health burden (3) . As a result, interventions that can be safely applied at the population level to prevent long-term weight gain would have major benefits to public health. It has been suggested that gradual adult weight gain can be the result of only a small habitual positive energy balance of 209·2-418·4 kJ/d (50-100 kcal/d) (4) . Consequently, an improved understanding of the hormonal and neuronal signals that control appetite regulation may facilitate the development of novel dietary strategies that supress energy intake and oppose a positive energy balance and long-term weight gain.Epidemiological and experimental studies have consistently highlighted an inverse association between dietary fibre intake and body weight gain (5)(6)(7) . Furthermore, an increased intake of dietary fibre has been associated with improved appetite regulation (8) , thus making high-fibre diets an attractive strategy to reduce obesity levels. The current definition of dietary fibre (9) encompasses a ...

Short Chain Fatty Acids Prevent High-fat-diet-induced Obesity in Mice by Regulating G Protein-coupled Receptors and Gut Microbiota

“…The production of SCFAs by microbial fermentation of dietary fibers is associated with a wide range of health benefits, including improvements in body composition, energy homeostasis, lipid profiles and reduced body weight, by stimulating multiple hormonal and neural pathways, such as appetite control, enhancement of oxidation and thermogenesis in muscle and liver tissues, and others6131415242526. However, no consistent conclusions have been reached on changes of gut SCFA production in obesity.…”

“…Numerous physiological and clinical studies have demonstrated that SCFAs are also a significant source of calories and have trophic effects on both the small and large bowel. Meanwhile, SCFAs may play beneficial roles in appetite regulation and lipid and glucose metabolism by epigenetically regulating related genes1314. SCFAs also act as signal transduction molecules and bind and activate orphan G-protein-coupled receptors, such as GPR43 and GPR41, which are also known as free fatty acid receptor 2 and 3 (FFAR2 and FFAR3), respectively.…”

Prebiotic Dietary Fiber and Gut Health: Comparing the In Vitro Fermentations of Beta-Glucan, Inulin and Xylooligosaccharide.

“…Although no mechanism has been identified, and studies show conflicting results [38], elevated serum propionate concentrations have been shown to have a hypocholesterolaemic effect [39]. Propionate may also play an influential role in satiety, although mechanisms still remain unclear [40,41]. Cholesterol-lowering properties of beta-glucans may be limited to effects from the upper-GI, although many propionate-producing bacteria have a preference to fermenting various types of beta-glucans (Bacteroides, Prevotella, Clostridium) based on the presence of genes responsible for endo-β-glucanase enzyme production [42].…”

The Gut Bacteria-Driven Obesity Development

“…SCFA production, principally acetate, propionate, and butyrate, is increased in obesity, in both animal models and humans [58]. SCFAs exert multiple beneficial effects on the host energy metabolism not only by improving the intestinal cell differentiation and proliferation but also by directly affecting various host peripheral tissues [59]. SCFAs, indeed, influence energy intake and metabolism through their binding to 2 G-protein-coupled receptors, free fatty acid receptor 2 (FFAR2 or GPR43) and free fatty acid receptor 3 (FFAR3 or GPR41) [60].…”