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Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model.
Nutrients. 2019 Nov 19; 11(11)N

Abstract

Despite affecting millions of patients worldwide, no pharmacological treatment has yet proved effective against non-alcoholic steatohepatitis (NASH) induced liver fibrosis. Current guidelines recommend lifestyle modifications including reductions in dietary energy intake. Recently, therapy with atorvastatin and vitamin E (vitE) has been recommended, although clinical studies on the resolution of hepatic fibrosis are inconclusive. Targeting NASH-induced hepatic end-points, this study evaluated the effects of atorvastatin and vitE alone or in combination with a dietary intervention in the guinea pig NASH model. Guinea pigs (n = 72) received 20 weeks of high fat feeding before allocating to four groups: continued HF feeding (HF), HF diet with atorvastatin and vitE (HF+), low-fat diet (LF) and low-fat with atorvastatin and vitE (LF+), for four or eight weeks of intervention. Both LF and LF+ decreased liver weight, cholesterol and plasma dyslipidemia. LF+ further improved hepatic histopathological hallmarks (p < 0.05), liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (p < 0.05) and reduced the expression of target genes of hepatic inflammation and fibrosis (p < 0.05), underlining an increased effect on NASH resolution in this group. Collectively, the data support an overall beneficial effect of diet change, and indicate that atorvastatin and vitE therapy combined with a diet change act synergistically in improving NASH-induced endpoints.

Authors+Show Affiliations

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.CV Research, Global Research, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

31752351

Citation

Klaebel, Julie Hviid, et al. "Atorvastatin and Vitamin E Accelerates NASH Resolution By Dietary Intervention in a Preclinical Guinea Pig Model." Nutrients, vol. 11, no. 11, 2019.
Klaebel JH, Skjødt M, Skat-Rørdam J, et al. Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model. Nutrients. 2019;11(11).
Klaebel, J. H., Skjødt, M., Skat-Rørdam, J., Rakipovski, G., Ipsen, D. H., Schou-Pedersen, A. M. V., Lykkesfeldt, J., & Tveden-Nyborg, P. (2019). Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model. Nutrients, 11(11). https://doi.org/10.3390/nu11112834
Klaebel JH, et al. Atorvastatin and Vitamin E Accelerates NASH Resolution By Dietary Intervention in a Preclinical Guinea Pig Model. Nutrients. 2019 Nov 19;11(11) PubMed PMID: 31752351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model. AU - Klaebel,Julie Hviid, AU - Skjødt,Mia, AU - Skat-Rørdam,Josephine, AU - Rakipovski,Günaj, AU - Ipsen,David H, AU - Schou-Pedersen,Anne Marie V, AU - Lykkesfeldt,Jens, AU - Tveden-Nyborg,Pernille, Y1 - 2019/11/19/ PY - 2019/10/14/received PY - 2019/11/13/revised PY - 2019/11/15/accepted PY - 2019/11/23/entrez PY - 2019/11/23/pubmed PY - 2020/6/2/medline KW - Non-alcoholic fatty liver disease KW - Non-alcoholic steatohepatitis KW - atorvastatin KW - fibrosis KW - hepatic lesions KW - lifestyle modifications KW - vitamin E JF - Nutrients JO - Nutrients VL - 11 IS - 11 N2 - Despite affecting millions of patients worldwide, no pharmacological treatment has yet proved effective against non-alcoholic steatohepatitis (NASH) induced liver fibrosis. Current guidelines recommend lifestyle modifications including reductions in dietary energy intake. Recently, therapy with atorvastatin and vitamin E (vitE) has been recommended, although clinical studies on the resolution of hepatic fibrosis are inconclusive. Targeting NASH-induced hepatic end-points, this study evaluated the effects of atorvastatin and vitE alone or in combination with a dietary intervention in the guinea pig NASH model. Guinea pigs (n = 72) received 20 weeks of high fat feeding before allocating to four groups: continued HF feeding (HF), HF diet with atorvastatin and vitE (HF+), low-fat diet (LF) and low-fat with atorvastatin and vitE (LF+), for four or eight weeks of intervention. Both LF and LF+ decreased liver weight, cholesterol and plasma dyslipidemia. LF+ further improved hepatic histopathological hallmarks (p < 0.05), liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (p < 0.05) and reduced the expression of target genes of hepatic inflammation and fibrosis (p < 0.05), underlining an increased effect on NASH resolution in this group. Collectively, the data support an overall beneficial effect of diet change, and indicate that atorvastatin and vitE therapy combined with a diet change act synergistically in improving NASH-induced endpoints. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/31752351/Atorvastatin_and_Vitamin_E_Accelerates_NASH_Resolution_by_Dietary_Intervention_in_a_Preclinical_Guinea_Pig_Model_ L2 - https://www.mdpi.com/resolver?pii=nu11112834 DB - PRIME DP - Unbound Medicine ER -