title: The role of mitochondrial glycerol-3-phosphate acyltransferase-1 in regulating lipid and glucose homeostasis in high-fat diet fed mice.
abstract: Glycerol-3-phosphate acyltransferase (GPAT) is involved in triacylglycerol (TAG) and phospholipid synthesis, catalyzing the first committed step. In order to further investigate the in vivo importance of the dominating mitochondrial variant, GPAT1, a novel GPAT1(-/-) mouse model was generated and studied. Female GPAT1(-/-) mice had reduced body weight-gain and adiposity when fed chow diet compared with littermate wild-type controls. Furthermore, GPAT1(-/-) females on chow diet showed decreased liver TAG content, plasma cholesterol and TAG levels and increased ex vivo liver fatty acid oxidation and plasma ketone bodies. However, these beneficial effects were abolished and the glucose tolerance tended to be impaired when GPAT1(-/-) females were fed a long-term high-fat diet (HFD). GPAT1-deficiency was not associated with altered whole body energy expenditure or respiratory exchange ratio. In addition, there were no changes in male GPAT1(-/-) mice fed either diet except for increased plasma ketone bodies on chow diet, indicating a gender-specific phenotype. Thus, GPAT1-deficiency does not protect against HFD-induced obesity, hepatic steatosis or whole body glucose intolerance.
authors.affiliation: AstraZeneca Research & Development, Pepparedsleden 1, S-431 83 Mölndal, Sweden.
authors.forename: Misak
authors.initials: M
authors.lastname: Yazdi
authors.forename: Andrea
authors.initials: A
authors.lastname: Ahnmark
authors.forename: Lena
authors.initials: L
authors.lastname: William-Olsson
authors.forename: Michael
authors.initials: M
authors.lastname: Snaith
authors.forename: Nigel
authors.initials: N
authors.lastname: Turner
authors.forename: Fredrik
authors.initials: F
authors.lastname: Osla
authors.forename: Marianne
authors.initials: M
authors.lastname: Wedin
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Asztély
authors.forename: Anders
authors.initials: A
authors.lastname: Elmgren
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly-Y
authors.forename: Sandra
authors.initials: S
authors.lastname: Schreyer
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindén
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005234:Fatty Liver / Q000209:etiology* / Q000235:genetics; D005260:Female; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000209:etiology* / Q000235:genetics; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000201:enzymology; D009765:Obesity / Q000209:etiology* / Q000235:genetics; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism*; D015430:Weight Gain
chemical_list: D004041:Dietary Fats; D014280:Triglycerides; D002784:Cholesterol; D005992:Glycerol-3-Phosphate O-Acyltransferase; D005947:Glucose