Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity

Preclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-a...

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Main Authors: Gabriella Sistilli, Veronika Kalendova, Tomas Cajka, Illaria Irodenko, Kristina Bardova, Marina Oseeva, Petr Zacek, Petra Kroupova, Olga Horakova, Karoline Lackner, Amalia Gastaldelli, Ondrej Kuda, Jan Kopecky, Martin Rossmeisl
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Nutrients
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Online Access:https://www.mdpi.com/2072-6643/13/2/437
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author Gabriella Sistilli
Veronika Kalendova
Tomas Cajka
Illaria Irodenko
Kristina Bardova
Marina Oseeva
Petr Zacek
Petra Kroupova
Olga Horakova
Karoline Lackner
Amalia Gastaldelli
Ondrej Kuda
Jan Kopecky
Martin Rossmeisl
author_facet Gabriella Sistilli
Veronika Kalendova
Tomas Cajka
Illaria Irodenko
Kristina Bardova
Marina Oseeva
Petr Zacek
Petra Kroupova
Olga Horakova
Karoline Lackner
Amalia Gastaldelli
Ondrej Kuda
Jan Kopecky
Martin Rossmeisl
author_sort Gabriella Sistilli
collection DOAJ
description Preclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-alcoholic fatty liver disease based on high-fat feeding at thermoneutral temperature. Male C57BL/6N mice were fed for 24 weeks a lard-based diet given either alone (LHF) or supplemented with Omega-3 (30 mg/g diet) as PLs (krill oil; ω3PL) or TAGs (Epax 3000TG concentrate; ω3TG), which had a similar total content of EPA and DHA and their ratio. Substantial levels of TAG accumulation (~250 mg/g) but relatively low inflammation/fibrosis levels were achieved in the livers of control LHF mice. Liver steatosis was reduced by >40% in the ω3PL but not ω3TG group, and plasma ALT levels were markedly reduced (by 68%) in ω3PL mice as well. Krill oil administration also improved hepatic insulin sensitivity, and its effects were associated with high plasma adiponectin levels (150% of LHF mice) along with superior bioavailability of EPA, increased content of alkaloids stachydrine and trigonelline, suppression of lipogenic gene expression, and decreased diacylglycerol levels in the liver. This study reveals that in addition to Omega-3 PLs, other constituents of krill oil, such as alkaloids, may contribute to its strong antisteatotic effects in the liver.
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spelling doaj.art-6cc4ea4956764e4381f0e749386d61082023-12-03T15:11:29ZengMDPI AGNutrients2072-66432021-01-0113243710.3390/nu13020437Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced ObesityGabriella Sistilli0Veronika Kalendova1Tomas Cajka2Illaria Irodenko3Kristina Bardova4Marina Oseeva5Petr Zacek6Petra Kroupova7Olga Horakova8Karoline Lackner9Amalia Gastaldelli10Ondrej Kuda11Jan Kopecky12Martin Rossmeisl13Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicProteomics Core Facility, Faculty of Science, Charles University, Division BIOCEV, Prumyslova 595, 25250 Vestec, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Pathology, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, AustriaCardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56100 Pisa, ItalyInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech RepublicPreclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-alcoholic fatty liver disease based on high-fat feeding at thermoneutral temperature. Male C57BL/6N mice were fed for 24 weeks a lard-based diet given either alone (LHF) or supplemented with Omega-3 (30 mg/g diet) as PLs (krill oil; ω3PL) or TAGs (Epax 3000TG concentrate; ω3TG), which had a similar total content of EPA and DHA and their ratio. Substantial levels of TAG accumulation (~250 mg/g) but relatively low inflammation/fibrosis levels were achieved in the livers of control LHF mice. Liver steatosis was reduced by >40% in the ω3PL but not ω3TG group, and plasma ALT levels were markedly reduced (by 68%) in ω3PL mice as well. Krill oil administration also improved hepatic insulin sensitivity, and its effects were associated with high plasma adiponectin levels (150% of LHF mice) along with superior bioavailability of EPA, increased content of alkaloids stachydrine and trigonelline, suppression of lipogenic gene expression, and decreased diacylglycerol levels in the liver. This study reveals that in addition to Omega-3 PLs, other constituents of krill oil, such as alkaloids, may contribute to its strong antisteatotic effects in the liver.https://www.mdpi.com/2072-6643/13/2/437NAFLDobesityomega-3krill oilphospholipidshigh-fat diet
spellingShingle Gabriella Sistilli
Veronika Kalendova
Tomas Cajka
Illaria Irodenko
Kristina Bardova
Marina Oseeva
Petr Zacek
Petra Kroupova
Olga Horakova
Karoline Lackner
Amalia Gastaldelli
Ondrej Kuda
Jan Kopecky
Martin Rossmeisl
Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity
Nutrients
NAFLD
obesity
omega-3
krill oil
phospholipids
high-fat diet
title Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity
title_full Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity
title_fullStr Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity
title_full_unstemmed Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity
title_short Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity
title_sort krill oil supplementation reduces exacerbated hepatic steatosis induced by thermoneutral housing in mice with diet induced obesity
topic NAFLD
obesity
omega-3
krill oil
phospholipids
high-fat diet
url https://www.mdpi.com/2072-6643/13/2/437
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