Liver Patt1 deficiency protects male mice from age-associated but not high-fat diet-induced hepatic steatosis.
Patt1 is a newly identified protein acetyltransferase that is highly expressed in liver. However, the role of Patt1 in liver is still unclear. We generated Patt1 liver-specific knockout (LKO) mice and mainly measured the effect of hepatic Patt1 deficiency on lipid metabolism. Hepatic Patt1 deficiency in male mice markedly decreases fat mass and dramatically alleviates age-associated accumulation of lipid droplets in liver. Moreover, hepatic Patt1 abrogation in male mice significantly reduces the liver triglyceride and free fatty acid levels, but it has no effect on liver cholesterol level, liver weight, and liver function. Consistently, primary cultured Patt1-deficient hepatocytes are resistant to palmitic acid-induced lipid accumulation, but hepatic Patt1 deficiency fails to protect male mice from high-fat diet-induced hepatic steatosis. Further studies show that hepatic Patt1 deficiency decreases fatty acid uptake, reduces lipid synthesis, and enhances fatty acid oxidation, which may contribute to the attenuated hepatic steatosis in Patt1 LKO mice. These results demonstrate that Patt1 plays an important role in hepatic lipid metabolism and have implications toward resolving age-associated hepatic steatosis.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Yang
Y
Liu
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Daizhan
D
Zhou
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Fang
F
Zhang
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Yanyang
Y
Tu
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Yulei
Y
Xia
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Hui
H
Wang
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Ben
B
Zhou
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Yi
Y
Zhang
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Jingxia
J
Wu
Model Animal Research Center, Nanjing University, Nanjing 210061, China.
Xiang
X
Gao
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and.
Zhishui
Z
He
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science; Graduate School of the Chinese Academy of Science; Shanghai 200031, China; and. Electronic address: qwzhai@sibs.ac.cn.
Qiwei
Q
Zhai
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D015151:Immunoblotting; D047468:Immunoprecipitation; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019308:Palmitic Acid / Q000009:adverse effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D019308:Palmitic Acid; D002784:Cholesterol; D000123:Acetyltransferases