Astaxanthin inhibits inflammation and fibrosis in the liver and adipose tissue of mouse models of diet-induced obesity and nonalcoholic steatohepatitis.

Abstract

The objective of this study was to determine if astaxanthin (ASTX), a xanthophyll carotenoid, can prevent obesity-associated metabolic abnormalities, inflammation and fibrosis in diet-induced obesity (DIO) and nonalcoholic steatohepatitis (NASH) mouse models. Male C57BL/6J mice were fed a low-fat (6% fat, w/w), a high-fat/high-sucrose control (HF/HS; 35% fat, 35% sucrose, w/w), or a HF/HS containing ASTX (AHF/HS; 0.03% ASTX, w/w) for 30 weeks. To induce NASH, another set of mice was fed a HF/HS diet containing 2% cholesterol (HF/HS/HC) a HF/HS/HC with 0.015% ASTX (AHF/HS/HC) for 18 weeks. Compared to LF, HF/HS significantly increased plasma total cholesterol, triglyceride and glucose, which were lowered by ASTX. ASTX decreased hepatic mRNA levels of markers of macrophages and fibrosis in both models. The effect of ASTX was more prominent in NASH than DIO mice. In epididymal fat, ASTX also decreased macrophage infiltration and M1 macrophage marker expression, and inhibited hypoxia-inducible factor 1-α and its downstream fibrogenic genes in both mouse models. ASTX significantly decreased tumor necrosis factor α mRNA in the splenocytes from DIO mice upon lipopolysaccharides stimulation compared with those from control mice fed an HF/HS diet. Additionally, ASTX significantly elevated the levels of genes that regulate fatty acid β-oxidation and mitochondrial biogenesis in the skeletal muscle compared with control obese mice, whereas no differences were noted in adipose lipogenic genes. Our results indicate that ASTX inhibits inflammation and fibrosis in the liver and adipose tissue and enhances the skeletal muscle's capacity for mitochondrial fatty acid oxidation in obese mice.

• Authors: Bohkyung Kim, Callie Farruggia, Chai Siah Ku, Tho X Pham, Yue Yang, Minkyung Bae, Casey J Wegner, Nicholas J Farrell, Ellen Harness, Young-Ki Park, Sung I Koo, Ji-Young Lee
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 43 Pg. 27-35 (05 2017) ISSN: 1873-4847 [Electronic] United States
• PMID: 28193580 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Lipids
• Xanthophylls
• astaxanthine

Topics

• Adipose Tissue (drug effects, metabolism, pathology)
• Animals
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Dietary Supplements
• Disease Models, Animal
• Fibrosis (prevention & control)
• Gene Expression Regulation (drug effects)
• Lipids (blood, genetics)
• Liver (drug effects, metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (pathology, prevention & control)
• Obesity (complications, etiology, prevention & control)
• Panniculitis (metabolism, pathology, prevention & control)
• Xanthophylls (pharmacology)