title: Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats.
abstract: The effect of hypertension on non-alcoholic fatty liver disease (NAFLD) remains unclear at the molecular level. In this study, we investigated the effects of hypertension on the degree of hepatic steatosis, liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined (CDAA) diet in spontaneously hypertensive rats (SHRs). Seven-week-old male SHRs were fed standard chow with high or normal salt concentrations for 7 weeks, followed by a CDAA diet containing high or normal salt for an additional 8 or 24 weeks. Hepatic steatosis was assessed using hepatic triglyceride levels and Oil red O staining. Hepatic fibrosis was evaluated using Sirius red and Azan staining. Systolic blood pressure (SBP) gradually increased with a high-salt diet and was significantly higher after 7 weeks of feeding with high-salt vs. normal-salt chow. After 8 weeks on the CDAA diet, the degree of hepatic steatosis did not differ between the high-salt and normal-salt groups; however, alanine aminotransferase and fasting blood glucose levels were significantly higher and hepatic mRNA levels for interleukin (IL)-10 and heme oxygenase (HO)-1 were significantly lower in the high-salt group compared with the normal-salt group. After 24 weeks on the CDAA diet, the high-salt group had significantly more severe hepatic fibrosis and a higher hepatic mRNA expression of α-smooth muscle actin and lower hepatic IL-10 and HO-1 mRNA levels compared with the normal-salt group. In conclusion, our results indicate that hypertension is a potential risk factor for liver injury and hepatic fibrosis through glucose intolerance and decreased IL-10-mediated or HO-1-induced anti-inflammatory mechanisms.
authors.affiliation: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Arima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Rie
authors.initials: R
authors.lastname: Ibusuki
authors.forename: Ryo
authors.initials: R
authors.lastname: Kumamoto
authors.forename: Shirou
authors.initials: S
authors.lastname: Tanoue
authors.forename: Seiichi
authors.initials: S
authors.lastname: Mawatari
authors.forename: Kohei
authors.initials: K
authors.lastname: Oda
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Numata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Makoto
authors.initials: M
authors.lastname: Oketani
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure; D002796:Choline Deficiency / Q000503:physiopathology*; D004032:Diet; D005234:Fatty Liver / Q000150:complications / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D016753:Interleukin-10; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000410:Alanine Transaminase