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- Title
Liver-Specific Overexpression of Prostasin Attenuates High-Fat Diet-Induced Metabolic Dysregulation in Mice.
- Authors
Sekine, Tetsuo; Takizawa, Soichi; Uchimura, Kohei; Miyazaki, Asako; Tsuchiya, Kyoichiro
- Abstract
The liver has a most indispensable role in glucose and lipid metabolism where we see some of the most serious worldwide health problems. The serine protease prostasin (PRSS8) cleaves toll-like receptor 4 (TLR4) and regulates hepatic insulin sensitivity under PRSS8 knockout condition. However, liver substrate proteins of PRSS8 other than TLR4 and the effect to glucose and lipid metabolism remain unclarified with hepatic elevation of PRSS8 expression. Here we show that high-fat-diet-fed liver-specific PRSS8 transgenic mice improved glucose tolerance and hepatic steatosis independent of body weight. PRSS8 amplified extracellular signal-regulated kinase phosphorylation associated with matrix metalloproteinase 14 activation in vivo and in vitro. Moreover, in humans, serum PRSS8 levels reduced more in type 2 diabetes mellitus (T2DM) patients than healthy controls and were lower in T2DM patients with increased maximum carotid artery intima media thickness (>1.1 mm). These results identify the regulatory mechanisms of PRSS8 overexpression over glucose and lipid metabolism, as well as excessive hepatic fat storage.
- Subjects
MATRIX metalloproteinases; INSULIN sensitivity; LIVER proteins; LIPID metabolism; TYPE 2 diabetes
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 15, p8314
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22158314