The role of mitochondrial glycerol-3-phosphate acyltransferase-1 in regulating lipid and glucose homeostasis in high-fat diet fed mice.
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.
Yazdi
Misak
M
AstraZeneca Research & Development, Pepparedsleden 1, S-431 83 Mölndal, Sweden.
Ahnmark
Andrea
A
William-Olsson
Lena
L
Snaith
Michael
M
Turner
Nigel
N
Osla
Fredrik
F
Wedin
Marianne
M
Asztély
Anna-Karin
AK
Elmgren
Anders
A
Bohlooly-Y
Mohammad
M
Schreyer
Sandra
S
Lindén
Daniel
D
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
D004041:Dietary Fats; D014280:Triglycerides; D002784:Cholesterol; D005992:Glycerol-3-Phosphate O-Acyltransferase; D005947:Glucose