The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of “indigestible” prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1–secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.

https://diabetes.diabetesjournals.org/content/diabetes/61/2/364.full.pdf

Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2

The connection between the gut microbiota and the aetiology of obesity and cardiometabolic disorders is increasingly being recognized by clinicians. Our gut microbiota might affect the cardiometabolic phenotype by fermenting indigestible dietary components and thereby producing short-chain fatty acids (SCFA). These SCFA are not only of importance in gut health and as signalling molecules, but might also enter the systemic circulation and directly affect metabolism or the function of peripheral tissues. In this Review, we discuss the effects of three SCFA (acetate, propionate and butyrate) on energy homeostasis and metabolism, as well as how these SCFA can beneficially modulate adipose tissue, skeletal muscle and liver tissue function. As a result, these SCFA contribute to improved glucose homeostasis and insulin sensitivity. Furthermore, we also summarize the increasing evidence for a potential role of SCFA as metabolic targets to prevent and counteract obesity and its associated disorders in glucose metabolism and insulin resistance. However, most data are derived from animal and in vitro studies, and consequently the importance of SCFA and differential SCFA availability in human energy and substrate metabolism remains to be fully established. Well-controlled human intervention studies investigating the role of SCFA on cardiometabolic health are, therefore, eagerly awaited.

Short-chain Fatty Acids in Control of Body Weight and Insulin Sensitivity

Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo11C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13C acetate above baseline levels. Hypothalamic 13C acetate regionally increases the 13C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic 13C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation.

/pdf/the-short-chain-fatty-acid-acetate-reduces-appetite-via-a-45df6jtvkb.pdf

The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism

The gut microbiota affects nutrient acquisition and energy regulation of the host, and can influence the development of obesity, insulin resistance, and diabetes. During feeding, gut microbes produce short-chain fatty acids, which are important energy sources for the host. Here we show that the short-chain fatty acid receptor GPR43 links the metabolic activity of the gut microbiota with host body energy homoeostasis. We demonstrate that GPR43-deficient mice are obese on a normal diet, whereas mice overexpressing GPR43 specifically in adipose tissue remain lean even when fed a high-fat diet. Raised under germ-free conditions or after treatment with antibiotics, both types of mice have a normal phenotype. We further show that short-chain fatty acid-mediated activation of GPR43 suppresses insulin signalling in adipocytes, which inhibits fat accumulation in adipose tissue and promotes the metabolism of unincorporated lipids and glucose in other tissues. These findings establish GPR43 as a sensor for excessive dietary energy, thereby controlling body energy utilization while maintaining metabolic homoeostasis.

/pdf/the-gut-microbiota-suppresses-insulin-mediated-fat-2il9toazdi.pdf

The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43

G protein-coupled receptor 43 (GPR43) has been identified as a receptor for short-chain fatty acids that include acetate and propionate. A potential involvement of GPR43 in immune and inflammatory response has been previously suggested because its expression is highly enriched in immune cells. GPR43 is also expressed in a number of other tissues including adipocytes; however, the functional consequences of GPR43 activation in these other tissues are not clear. In this report, we focus on the potential functions of GPR43 in adipocytes. We show that adipocytes treated with GPR43 natural ligands, acetate and propionate, exhibit a reduction in lipolytic activity. This inhibition of lipolysis is the result of GPR43 activation, because this effect is abolished in adipocytes isolated from GPR43 knockout animals. In a mouse in vivo model, we show that the activation of GPR43 by acetate results in the reduction in plasma free fatty acid levels without inducing the flushing side effect that has been observed by the activation of nicotinic acid receptor, GPR109A. These results suggest a potential role for GPR43 in regulating plasma lipid profiles and perhaps aspects of metabolic syndrome.

/pdf/activation-of-g-protein-coupled-receptor-43-in-adipocytes-3rr2bfx27r.pdf

Activation of G Protein-Coupled Receptor 43 in Adipocytes Leads to Inhibition of Lipolysis and Suppression of Plasma Free Fatty Acids

Mass-Transfer Control for Selective Deposition of Well-Dispersed Aupd Cocatalysts to Boost Photocatalytic H2o2 Production of Bivo4

The modification of Pd cocatalysts is considered to be an effective strategy to improve H2O2 production of photocatalysts because it can accelerate the reaction rate of O2 reduction. However, the strong adsorption between O2 molecules and Pd atoms is not conducive to the formation of intermediate HOO* and leads to the further reduction of H2O2 to H2O, thus limiting the improvement of H2O2 production. To solve the issue, in this work, Cu–Pd alloy cocatalysts are selectively modified on the electron‐rich facets of BiVO4 via facile photoinduced deposition and subsequent galvanic displacement. DFT calculations indicate that the incorporation of Cu atoms to Pd atoms weakens the oxygen adsorption energy and HOO* binding energy on Pd atom surfaces, thus increasing the activity and selectivity of O2 reduction to H2O2. Further experimental results show that the optimized Cu‐Pd/BiVO4(5:1) photocatalyst exhibits markedly boosted activity for H2O2 production (2189 µmol L‐1), which is 3.2‐fold higher than that of BiVO4 with modification of 0.3 wt% Pd cocatalyst (675 µmol L‐1). Additionally, the incorporation of metal Cu enables the economic utilization of Pd atoms and reduces the expense of the Pd cocatalyst.

Optimizing Oxygen and Intermediate HOO* Adsorption of Cu–Pd Alloy Cocatalyst for Boosting Photocatalytic H2O2 Production of BiVO4

A Novel Electrochemical Sensor Based on Cuo-Ceo2/Mxene Nanocomposite for Quantitative and Continuous Detection of H2o2

A double reaction system induced electrochemiluminescence enhancement based on SnS2 QDs@MIL-101 for ultrasensitive detection of CA242.

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