期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 22, 页码 12359-12367出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1918445117
关键词
adipocytes; hepatocytes; hepatocyte growth factor; hepsin
资金
- National Institutes of Health [HL126697, DK120679, AA024333, HL147823]
- American Heart Association [19POST34380460]
- National Natural Science Foundation of China [81873566]
- Priority Academic Program Development of Jiangsu Higher Education Institutes in China
Hepsin is a transmembrane serine protease primarily expressed in the liver. To date, the physiological function of hepsin remains poorly defined. Here we report that hepsin-deficient mice have low levels of blood glucose and lipids and liver glycogen, but increased adipose tissue browning and basal metabolic rates. The phenotype is caused by reduced hepatocyte growth factor activation and impaired Met signaling, resulting in decreased liver glucose and lipid metabolism and enhanced adipocyte browning. Hepsin-deficient mice exhibit marked resistance to high-fat diet-induced obesity, hyperglycemia, and hyperlipidemia. In db/db mice, hepsin deficiency ameliorates obesity and diabetes. These data indicate that hepsin is a key regulator in liver metabolism and energy homeostasis, suggesting that hepsin could be a therapeutic target for treating obesity and diabetes.
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