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• W4225492771 abstract "Abstract Mutations in the TAFAZZIN gene result in the X-linked genetic disease Barth Syndrome. The protein product tafazzin is a transacylase enzyme that remodels the phospholipid cardiolipin with fatty acids. Some Barth syndrome boys exhibit a lean phenotype. In addition, whole body knockdown of tafazzin in mice protects them from diet-induced obesity through increased hepatic fatty acid oxidation and reduced basal insulin secretion. We thus hypothesized that tafazzin deficiency in both the liver and beta cells of the pancreas contribute to this lean phenotype. Through a Cre-Lox approach we generated control, liver-specific, pancreatic beta cell-specific and liver and pancreatic beta cell-specific double knockout male mice. The animals were fed a high fat diet for 8 weeks and body weight, liver weight and fat pad weights determined. Liver-specific or pancreatic beta cell-specific male tafazzin knockout mice accumulated weight gain (≍40% increase in body weight) at the same rate as control animals. In contrast, the liver- and beta cell-specific double tafazzin knockout mice exhibited a reduced rate of weight gain by 8 weeks (≍26% increase in body weight) compared to control or the single tafazzin knockout animals. In addition, at 8 weeks the double tafazzin knockout mice exhibited reduced weight gain in tissues known to accumulate fat including the liver, the gonadal, inguinal and perirenal white adipose tissues and the brown adipose tissue. Thus, liver- and pancreatic beta cell-specific double tafazzin knockout male mice are protected from high fat diet induced weight gain and fat accumulation. These results may partially explain why some Barth Syndrome boys exhibit a lean phenotype." @default.
• W4225492771 created "2022-05-05" @default.
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• W4225492771 date "2022-04-19" @default.
• W4225492771 modified "2023-09-27" @default.
• W4225492771 title "Tissue Specific Knockout of the Cardiolipin Transacylase Enzyme TAFAZZIN in Both Liver and Pancreatic Beta Cells Protects Mice From Diet-Induced Obesity" @default.
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• W4225492771 doi "https://doi.org/10.1101/2022.04.19.488810" @default.
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