Salusin-α attenuates hepatic steatosis and atherosclerosis in high fat diet-fed low density lipoprotein receptor deficient mice.

Abstract

Salusin-α is an endogenous bioactive peptide and likely to prevent atherosclerosis. But its protective effect against atherosclerosis in vivo remains poorly understood. The aim of the present study was to determine the potential effects of salusin-α on atherosclerosis and its associated metabolic disorders in high fat diet (HFD)-fed low density lipoprotein receptor deficient (LDLr-/-) mice, and also explore the possible underlying mechanisms involved. Our data showed that after 12 weeks treatment, salusin-α ameliorated HFD-induced weight gain, hyperlipidemia, and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Salusin-α suppressed HFD-induced hepatic steatosis and regulated gene expression of fatty acid synthase, acetyl coenzyme A carboxylase-α, peroxisome proliferator-activated receptor-α, camitine palmitoyltransferase-1α and CYP7A1 in liver. Salusin-α reduced atherosclerotic plaque area and macrophage foam cell formation. Salusin-α prevented hepatic and aortic inflammation as evidenced by the reduced macrophage recruitment and mRNA expression of IL-6 and TNF-α in both liver and aorta. Salusin-α also reduced hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in liver and suppressing reactive oxygen species generation and protein expressions of NADPH-oxidase (NOX) 2 and NOX4 in both liver and aorta. Our present data suggest that salusin-α could reduce hepatic steatosis and atherosclerosis via its pleiotropic effects, including amelioration of lipid profiles, regulation of some key molecules involved in lipid metabolism in liver, anti-oxidative effect and anti-inflammatory action.

• Authors: Kun Tang, Fei Wang, Yi Zeng, XueMeng Chen, XiaoLe Xu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 830 Pg. 76-86 (Jul 05 2018) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 29704496 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Intercellular Signaling Peptides and Proteins
• Interleukin-6
• Lipids
• PPAR alpha
• Receptors, LDL
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse
• Acetyl Coenzyme A
• Cholesterol 7-alpha-Hydroxylase
• Cyp7a1 protein, mouse
• Carnitine O-Palmitoyltransferase
• Fatty Acid Synthases

Topics

• Acetyl Coenzyme A (genetics)
• Animals
• Atherosclerosis (blood, drug therapy, genetics)
• Carnitine O-Palmitoyltransferase (genetics)
• Cholesterol 7-alpha-Hydroxylase (genetics)
• Diet, High-Fat
• Fatty Acid Synthases (genetics)
• Fatty Liver (blood, drug therapy, genetics)
• Hyperlipidemias (blood, drug therapy)
• Intercellular Signaling Peptides and Proteins (pharmacology, therapeutic use)
• Interleukin-6 (blood)
• Lipids (blood)
• Male
• Mice, Knockout
• PPAR alpha (genetics)
• Receptors, LDL (genetics)
• Tumor Necrosis Factor-alpha (blood)
• Weight Gain (drug effects)