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

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 437
Author(s):  
Gabriella Sistilli ◽  
Veronika Kalendova ◽  
Tomas Cajka ◽  
Illaria Irodenko ◽  
Kristina Bardova ◽  
...  

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.


2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Mi Tian ◽  
Jingjing Wang ◽  
Shangming Liu ◽  
Xinyun Li ◽  
Jingyuan Li ◽  
...  

AbstractThe liver plays an important role in lipid and glucose metabolism. Here, we show the role of human antigen R (HuR), an RNA regulator protein, in hepatocyte steatosis and glucose metabolism. We investigated the level of HuR in the liver of mice fed a normal chow diet (NCD) and a high-fat diet (HFD). HuR was downregulated in the livers of HFD-fed mice. Liver-specific HuR knockout (HuRLKO) mice showed exacerbated HFD-induced hepatic steatosis along with enhanced glucose tolerance as compared with control mice. Mechanistically, HuR could bind to the adenylate uridylate-rich elements of phosphatase and tensin homolog deleted on the chromosome 10 (PTEN) mRNA 3′ untranslated region, resulting in the increased stability of Pten mRNA; genetic knockdown of HuR decreased the expression of PTEN. Finally, lentiviral overexpression of PTEN alleviated the development of hepatic steatosis in HuRLKO mice in vivo. Overall, HuR regulates lipid and glucose metabolism by targeting PTEN.



2015 ◽  
Vol 6 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Michael L. Kagan ◽  
Aharon Levy ◽  
Alicia Leikin-Frenkel

An oil from micro-algae rich in EPA with no DHA and consisting of 15% polar lipids (phospholipids and glycolipids) showed equivalent uptake of EPA into rat plasma and organs as omega-3 krill oil consisting of EPA and DHA and 40% phospholipids.



Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1281
Author(s):  
Valentina Cossiga ◽  
Vincenzo Lembo ◽  
Cecilia Nigro ◽  
Paola Mirra ◽  
Claudia Miele ◽  
...  

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.





eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Simon T Hui ◽  
Brian W Parks ◽  
Elin Org ◽  
Frode Norheim ◽  
Nam Che ◽  
...  

To identify genetic and environmental factors contributing to the pathogenesis of non-alcoholic fatty liver disease, we examined liver steatosis and related clinical and molecular traits in more than 100 unique inbred mouse strains, which were fed a diet rich in fat and carbohydrates. A >30-fold variation in hepatic TG accumulation was observed among the strains. Genome-wide association studies revealed three loci associated with hepatic TG accumulation. Utilizing transcriptomic data from the liver and adipose tissue, we identified several high-confidence candidate genes for hepatic steatosis, including Gde1, a glycerophosphodiester phosphodiesterase not previously implicated in triglyceride metabolism. We confirmed the role of Gde1 by in vivo hepatic over-expression and shRNA knockdown studies. We hypothesize that Gde1 expression increases TG production by contributing to the production of glycerol-3-phosphate. Our multi-level data, including transcript levels, metabolite levels, and gut microbiota composition, provide a framework for understanding genetic and environmental interactions underlying hepatic steatosis.



2021 ◽  
Author(s):  
Katarzyna Kozlowska-Petriczko ◽  
Ewa Wunsch ◽  
Jan Petriczko ◽  
Wing-Kin Syn ◽  
Piotr Milkiewicz

Abstract Background & Aims: In view of limited reliability of the biopsy in the assessment of liver fat, a non-invasive, trustworthy and more accessible method estimating a degree of steatosis is urgently needed. While controlled attenuation parameter (CAP) is used to quantify hepatic fat, its availability in routine practice is limited. Therefore, the aim of this study was to compare the diagnostic accuracy of biomarker- and ultrasound-based techniques for the diagnosis and grading of hepatic steatosis. Methods: This was a prospective study of 167 adults with and without non-alcoholic fatty liver disease. As measured against CAP, we assessed Hamaguchi’s score and the hepatorenal index (HRI), and the following biochemical measures: the fatty liver index, hepatic steatosis index and lipid accumulation product scores during a single out-patient visit. Area under the receiver operating curve (AUROC) analyses were used to evaluate the diagnostic accuracy of each test and to calculate optimal thresholds for the ultrasound techniques. Results: All non-invasive methods displayed high accuracy in detecting steatosis (mean AUC value ≥ 0.90), with Hamaguchi’s score and the HRI as the most precise. These two tests also had the highest sensitivity and specificity (82.2% and 100%; 86.9% and 94.8%, respectively). We propose new thresholds for Hamaguchi’s score and HRI for hepatic steatosis grading, indicated by optimal sensitivity and specificity. Conclusion: Ultrasound-based techniques are the most accurate for assessing liver steatosis compared to other non-invasive tests. Given the accessibility of ultrasonography, this finding is of practical importance for the assessment of liver steatosis in clinical settings.



Gut ◽  
2020 ◽  
Vol 69 (12) ◽  
pp. 2193-2202 ◽  
Author(s):  
Justine Vily-Petit ◽  
Maud Soty-Roca ◽  
Marine Silva ◽  
Margaux Raffin ◽  
Amandine Gautier-Stein ◽  
...  

ObjectiveHepatic steatosis accompanying obesity is a major health concern, since it may initiate non-alcoholic fatty liver disease (NAFLD) and associated complications like cirrhosis or cancer. Intestinal gluconeogenesis (IGN) is a recently described function that contributes to the metabolic benefits of specific macronutrients as protein or soluble fibre, via the initiation of a gut-brain nervous signal triggering brain-dependent regulations of peripheral metabolism. Here, we investigate the effects of IGN on liver metabolism, independently of its induction by the aforementioned macronutrients.DesignTo study the specific effects of IGN on hepatic metabolism, we used two transgenic mouse lines: one is knocked down for and the other overexpresses glucose-6-phosphatase, the key enzyme of endogenous glucose production, specifically in the intestine.ResultsWe report that mice with a genetic overexpression of IGN are notably protected from the development of hepatic steatosis and the initiation of NAFLD on a hypercaloric diet. The protection relates to a diminution of de novo lipogenesis and lipid import, associated with benefits at the level of inflammation and fibrosis and linked to autonomous nervous system. Conversely, mice with genetic suppression of IGN spontaneously exhibit increased hepatic triglyceride storage associated with activated lipogenesis pathway, in the context of standard starch-enriched diet. The latter is corrected by portal glucose infusion mimicking IGN.ConclusionWe conclude that IGN per se has the capacity of preventing hepatic steatosis and its eventual evolution toward NAFLD.



2015 ◽  
Vol 16 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Nemanja Jovicic ◽  
Ilija Jeftic ◽  
Marina Miletic Kovacevic ◽  
Irena Tanaskovic ◽  
Nebojsa Arsenijevic ◽  
...  

ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity, but the molecular mechanisms of liver steatosis and its progression to non-alcoholic steatohepatitis and fibrosis are incompletely understood. Immune reactivity plays an important role in the pathogenesis of NAFLD. The IL-33/ST2 axis has a protective role in adiposity and atherosclerosis, but its role in obesity-associated metabolic disorders requires further clarification. To investigate the unresolved role of IL-33/ST2 signalling in NAFLD, we used ST2-deficient (ST2-/-) and wild type (WT) BALB/c mice maintained on a high-fat diet (HFD) for 24 weeks. HFD-fed ST2-/- mice exhibited increased weight gain, visceral adipose tissue weight and triglyceridaemia and decreased liver weight compared with diet-matched WT mice. Compared with WT mice on an HFD, ST2 deletion significantly reduced hepatic steatosis, liver inflammation and fibrosis and downregulated the expression of genes related to lipid metabolism in the liver. The frequency of innate immune cells in the liver, including CD68+ macrophages and CD11c+ dendritic cells, was lower in HFD-fed ST2-/- mice, accompanied by lower TNFα serum levels compared with diet-matched WT mice. Less collagen deposition in the livers of ST2-/- mice on an HFD was associated with lower numbers of profibrotic CD11b+Ly6clow monocytes and CD4+IL-17+ T cells in the liver, lower hepatic gene expression of procollagen, IL-33 and IL-13, and lower serum levels of IL-33 and IL-13 compared with diet-matched WT mice.Our findings suggest that the IL-33/ST2 axis may have a complex role in obesity-associated metabolic disorders. Although it is protective in HFD-induced adiposity, the IL-33/ST2 pathway promotes hepatic steatosis, inflammation and fibrosis.



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