C-type natriuretic peptide (CNP) in endothelial cells attenuates hepatic fibrosis and inflammation in non-alcoholic steatohepatitis.

Abstract

AIMS:

Our previous study revealed that mice transgenic for endothelial-cell-specific overexpression of CNP (E-CNP Tg mice) are protected against the increased fat weight, inflammation, and insulin resistance associated with high-fat diet (HFD)-induced obesity. In addition, E-CNP overexpression prevented abnormal lipid profiles and metabolism and blocked inflammation in the livers of HFD-fed mice. Because obesity, dyslipidemia, and insulin resistance increase the risk of various liver diseases, including non-alcoholic steatohepatitis (NASH), we here studied the role of E-CNP overexpression in the livers of mice in which NASH was induced through feeding of either HFD or a choline-deficient defined l‑amino-acid diet (CDAA).

MAIN METHODS:

Wild-type (Wt) and E-CNP Tg mice were fed either a standard diet or HFD for 25 weeks or CDAA for 10 weeks. We then assessed hepatic and serum biochemistry; measured blood glucose during glucose tolerance test (GTT) and insulin tolerance test (ITT); evaluated hepatic fibrosis and inflammation; and performed hepatic histology and gene expression analysis.

KEY FINDINGS:

Serum triglycerides, total cholesterol, non-esterified fatty acids, asparagine transaminase, glucose tolerance, and insulin resistance were ameliorated by CNP overexpression in endothelial cells of HFD-fed E-CNP Tg mice. In addition, hepatic fibrosis and inflammation were decreased in HFD-fed E-CNP Tg mice compared with HFD-fed Wt mice. CDAA-fed E-CNP Tg mice showed improved glycemic control, but liver parameters, fibrosis, and inflammation were remained elevated and equivalent to those in CDAA-fed Wt mice.

SIGNIFICANCE:

The overexpression of CNP in endothelial cells has anti-fibrotic and anti-inflammatory effects in liver during HFD-induced NASH in mice.

• Authors: Cho-Rong Bae, Jun Hino, Hiroshi Hosoda, Mikiya Miyazato, Kenji Kangawa
• Journal: Life sciences (Life Sci) Vol. 209 Pg. 349-356 (Sep 15 2018) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 30114411 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Natriuretic Peptide, C-Type

Topics

• Animals
• Blood Glucose
• Cells, Cultured
• Choline Deficiency (complications)
• Diet, High-Fat (adverse effects)
• Endothelial Cells (cytology, metabolism)
• Glucose Tolerance Test
• Inflammation (etiology, pathology, prevention & control)
• Insulin Resistance
• Liver Cirrhosis (etiology, pathology, prevention & control)
• Male
• Mice
• Mice, Transgenic
• Natriuretic Peptide, C-Type (metabolism)
• Non-alcoholic Fatty Liver Disease (chemically induced, physiopathology)