title: Male mice that lack the G-protein-coupled receptor GPR41 have low energy expenditure and increased body fat content.
abstract: SCFA are produced in the gut by bacterial fermentation of undigested carbohydrates. Activation of the Gαi-protein-coupled receptor GPR41 by SCFA in β-cells and sympathetic ganglia inhibits insulin secretion and increases sympathetic outflow, respectively. A possible role in stimulating leptin secretion by adipocytes is disputed. In the present study, we investigated energy balance and glucose homoeostasis in GPR41 knockout mice fed on a standard low-fat or a high-fat diet. When fed on the low-fat diet, body fat mass was raised and glucose tolerance was impaired in male but not female knockout mice compared to wild-type mice. Soleus muscle and heart weights were reduced in the male mice, but total body lean mass was unchanged. When fed on the high-fat diet, body fat mass was raised in male but not female GPR41 knockout mice, but by no more in the males than when they were fed on the low-fat diet. Body lean mass and energy expenditure were reduced in male mice but not in female knockout mice. These results suggest that the absence of GPR41 increases body fat content in male mice. Gut-derived SCFA may raise energy expenditure and help to protect against obesity by activating GPR41.
authors.affiliation: Clore Laboratory, University of Buckingham, Buckingham MK18 1EG, UK.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bellahcene
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: O'Dowd
authors.forename: Ed T
authors.initials: ET
authors.lastname: Wargent
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Zaibi
authors.forename: David C
authors.initials: DC
authors.lastname: Hislop
authors.forename: Robert A
authors.initials: RA
authors.lastname: Ngala
authors.forename: David M
authors.initials: DM
authors.lastname: Smith
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cawthorne
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Stocker
authors.forename: Jonathan R S
authors.initials: JR
authors.lastname: Arch
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000378:metabolism; D001823:Body Composition / Q000235:genetics*; D001825:Body Fluid Compartments / Q000187:drug effects / Q000378:metabolism; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology*; D004734:Energy Metabolism / Q000235:genetics*; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology; D018149:Glucose Intolerance / Q000235:genetics; D006321:Heart / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D009929:Organ Size; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors
chemical_list: D004041:Dietary Fats; D005232:Fatty Acids, Volatile; C506482:Gpcr41 protein, mouse; D007328:Insulin; D020738:Leptin; D043562:Receptors, G-Protein-Coupled