Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids

Nilsson, Niclas; Kotarsky, Knut; Owman, Christer; Olde, Björn

doi:10.1016/s0006-291x(03)00488-1

Cited by 479 publications

(466 citation statements)

References 26 publications

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“…In 2003, it was demonstrated that SCFA act as ligands for the previously orphaned G-protein-coupled receptors GPR41 and GPR43 (29)(30)(31) . These receptors have since been renamed free fatty acid receptor (FFAR) 3 and FFAR2, respectively.…”

Section: Scfa Receptors and Anorectic Gut Hormone Releasementioning

confidence: 99%

“…Both FFAR2 and FFAR3 are activated by physiological concentrations of SCFA, although a preference of FFAR2 for acetate and propionate and of FFAR3 for propionate and butyrate has been reported (29)(30)(31) . These receptors have been shown to be expressed not only in the gut epithelium (32,33) where SCFA are produced and are at their highest concentrations, but also at multiple tissue sites, including adipose tissue (34)(35)(36) , immune cells (29) , skeletal muscle (31) and within the peripheral nervous system (37,38) . A possible role for these receptors in energy intake regulation emerged with the identification that FFAR2 and FFAR3 are present on colonic endocrine L-cells (32,33) .…”

Section: Scfa Receptors and Anorectic Gut Hormone Releasementioning

confidence: 99%

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

2014

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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 ...

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Section: Scfa Receptors and Anorectic Gut Hormone Releasementioning

confidence: 99%

Section: Scfa Receptors and Anorectic Gut Hormone Releasementioning

confidence: 99%

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

2014

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“…In 2003, two orphan G-protein coupled receptors, FFA2 and FFA3 were identified as being activated by SCFA (21)(22)(23) . FFA2 and FFA3 were originally known as GPR43 and GPR41, respectively (24) .…”

Section: The Scfa Receptorsmentioning

confidence: 99%

Do SCFA have a role in appetite regulation?

2011

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The recently discovered SCFA-activated G-coupled protein receptors FFA receptor 2 and FFA receptor 3 are co-localised in L-cells with the anorexigenic 'ileal brake' gut hormone peptide YY, and also in adipocytes, with activation stimulating leptin release. Thus, SCFA such as acetate and propionate show promise as a candidate to increase satiety-enhancing properties of food. We therefore postulate SCFA may have a role in appetite regulation and energy homeostasis. SCFA can be delivered either directly within food, or indirectly via the colon by the provision of fermentable non-digestible carbohydrates. A review of studies investigating the effects of oral SCFA ingestion on appetite suggests that while oral SCFA ingestion is associated with enhanced satiety, this may be explained by product palatability rather than a physiological effect of SCFA. Colon-derived SCFA generated during microfloral fermentation have also been suggested to explain satiety-enhancing properties of non-digestible carbohydrates. However, findings are mixed from investigations into the effects of the prebiotic inulintype fructans on appetite. Overall, data presented in this review do not support a role for SCFA in appetite regulation.Acetate: Propionate: Acetic acid: Propionic acid: SCFA: Inulin: Oligofructose: Satiety Human subjects are living in an increasingly 'obesogenic' environment with easily accessed, energy dense foods and sedentary lifestyles. These 'obesogenic' factors can override homeostatic systems resulting in a gradual increase in the population body weight (BW) (1) . The need for strategies to prevent the rise in obesity is therefore becoming increasingly urgent. One strategy is to identify and develop foods that enhance satiety, thereby reducing subsequent energy intake (EI) (2,3) .SCFA have been suggested to have satiety-enhancing properties, with some researchers suggesting SCFA may explain the inverse association between dietary fibre intake and BW found in some observational studies (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) . This review considers the evidence for SCFA having a role in appetite regulation, starting first with the description of SCFA, followed by a discussion of the SCFA-activated receptors FFA receptor 2 (FFA2) and FFA receptor 3 (FFA3), which provide a rationale that SCFA may have a role in energy homeostasis. Finally, studies that have investigated the effects of orally and colonically delivered SCFA on appetite are reviewed. SCFASCFA are organic fatty acids generated in the colon when non-digestible carbohydrates (NDC) such as dietary fibre, resistant starch and inulin resist digestion and absorption in the small intestine, instead proceeding to the colon to undergo bacterial fermentation. The SCFA formed comprise between one and seven carbon units, with acetate (two carbon units) being the most predominant anion in the colon, followed by propionate (three carbon units) and then Abbreviations: AUC, area under curve; BW, body weight; DP, degree of polymerisation; EI, energy intake; GLP-1, glucago...

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“…However, this is now thought to represent a pseudogene that is unlikely to be expressed as a functional protein [17]. GPR40 is abundantly expressed in pancreatic β-cells (see below) but GPR41 may be predominantly localised on immune cells [18] and GPR43 on adipocytes [19]. In addition to these molecules, certain structurally more divergent receptors whose ligands are free or derivatised fatty acids are encoded elsewhere in the genome, including GPR84, GPR119 and GPR120 [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

Morgan¹,

Dhayal²

2009

Biochemical Pharmacology

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It is increasingly clear that some of the effects of both free and derivatised long chain fatty acids in pancreatic beta-cells are mediated by a group of G-protein coupled receptors. Some of these display close structural homology while others are more divergent. This Commentary reviews the expression and functional roles of three such molecules, GPR40, GPR119 and GPR120. GPR40 is the best characterised of this group and appears to mediate the acute stimulatory effects of long chain fatty acids on insulin secretion. GPR40 has also been proposed as a potential mediator of fatty acid toxicity but this is more controversial. GPR119 is also involved in stimulation of insulin secretion and responds primarily to ethanolamine derivatives of long chain fatty acids and also to some lysophospholipids rather than to free fatty acids. It may represent a useful target for the development of new insulin secretagogues aimed to enhance insulin release in patients with type 2 diabetes. GPR120 is the most enigmatic of the lipid responsive cell-surface receptors and its function remains to be established. It has been proposed to play a cytoprotective role in certain other cell types but it is unclear whether it fulfils a similar function in beta-cells.

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Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids

Cited by 479 publications

References 26 publications

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

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

Do SCFA have a role in appetite regulation?

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

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