Atorvastatin and vitamin e accelerates NASH resolution by dietary intervention in a preclinical guinea pig model
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Atorvastatin and vitamin e accelerates NASH resolution by dietary intervention in a preclinical guinea pig model. / Klaebel, Julie Hviid; Skjødt, Mia; Skat-Rørdam, Josephine; Rakipovski, Günaj; Ipsen, David H.; Schou-Pedersen, Anne Marie V.; Lykkesfeldt, Jens; Tveden-Nyborg, Pernille.
In: Nutrients, Vol. 11, No. 11, 2834, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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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
PY - 2019
Y1 - 2019
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.
AB - 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.
KW - Atorvastatin
KW - Fibrosis
KW - Hepatic lesions
KW - Lifestyle modifications
KW - Non-alcoholic fatty liver disease
KW - Non-alcoholic steatohepatitis
KW - Vitamin E
U2 - 10.3390/nu11112834
DO - 10.3390/nu11112834
M3 - Journal article
C2 - 31752351
AN - SCOPUS:85075453157
VL - 11
JO - Nutrients
JF - Nutrients
SN - 2072-6643
IS - 11
M1 - 2834
ER -
ID: 234220849