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Emerging Targets to Relieve Fat Stress-Induced Liver Diseases: UDCA, Tocotrienol, ω-3 PUFAs, and IgY Targeted NPC1L1 Cholesterol Transporter.

Posted by on in 2017
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Cha JY1Park JM2Lee HJ1Bae JS1Han YM2Oh BC1Ko KH3Hahm KB4. 2017. Curr Pharm Des. 23(27):3941-3951. doi: 10.2174/1381612823666170714124824.

1
Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon. Korea.
2
CHA Cancer Prevention Research Center, CHA Bio Complex, CHA University, Seongnam. Korea.
3
Digestive Disease Center, CHA University Bundang Medical Center, Seongnam. Korea.
4
CHA Cancer Prevention Research Center, CHA Bio Complex and CHA University Bundang Medical Center, Seongnam, 463-838. Korea.

Abstract

Fat stress-induced liver disease is a hepatic manifestation of metabolic syndrome initiated by excess fat accumulation and encompasses a wide spectrum of diseases from non-alcoholic fatty liver disease to nonalcoholic steatohepatitis, a precursor lesion progressing to more aggressive liver cirrhosis and hepatocellular carcinoma. Although the incidence of these fat stress-induced liver diseases is rapidly increasing worldwide in parallel with the growing epidemics of obesity and metabolic diseases, its exact pathogenesis is not well defined. Although obesity, sedentary life-style, altered dietary pattern, insulin resistance, altered intestinal barrier function, inflammatory cytokines, and oxidative stress have been acknowledged as contributing factors because of the indefinite pathogenesis of metabolic diseases, the only reliable treatment is lifestyle intervention composed of restrictive diet and exercise. Additionally, some existing medications such as pioglitazone and antioxidants such as vitamin E were reported to be effective; in this review, several novel agents especifically targeting nonalcoholic fatty liver disease pathogenesis under clinical trial will be introduced. These include an NPC1L1 blocker (ezetimibe), which significantly improved histological and symptomatic scores associated with steatohepatitis and fibrosis; clofibrate, phentoxyfylline, ursodeoxycholic acid, and tocopherol, all of which are prescribed to relieve fat stress; and additional IgY targeted NPC1L1, tocotrienol, ursodeoxycholic acid, and ω-3 polyunsaturated fatty acids, which are actively under investigation to confirm the safety of long-term use.

KEYWORDS:

IgY targeted NPC1L1; Non-alcoholic fatty liver disease; fatty acids; liver fibrosis; non-alcoholic steatohepatitis; pharmacological therapy; tocotrienol; ursodeoxycholic acid

PMID:
 
28714405
 
DOI:
 
10.2174/1381612823666170714124824
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