n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD

Vauzour, David; Rodríguez-Ramiro, Ildefonso; Rushbrook, Simon; Ipharraguerre, I.R.; Bevan, Damon; Davies, Susan; Tejera, Noemı́; Mena, Pedro; Pascual‐Teresa, Sonia de; Rio, Daniele Del; Gavrilović, Jelena; Minihane, Anne Marie

doi:10.1016/j.bbadis.2017.10.002

Cited by 26 publications

(20 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KO mice exhibited a higher plasma lipid content than the WT controls, suggesting that BAP31 deficiency impairs exogenous lipid clearance (Figure 4C). Fatty acid transporters, including cluster of differentiation 36 ( CD36 ), fatty acid transport protein 5 ( FATP5 ), and membrane-associated fatty acid binding protein ( FABPpm ), which are responsible for fatty acid transportation across the plasma membrane of hepatocytes [22], were significantly reduced after Tm administration. FATP5 and FABPpm were decreased more in KO than in WT mice.…”

Section: Resultsmentioning

confidence: 99%

Induction of Liver Steatosis in BAP31-Deficient Mice Burdened with Tunicamycin-Induced Endoplasmic Reticulum Stress

Yang

Jiang

et al. 2018

IJMS

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress is highly associated with liver steatosis. B-cell receptor-associated protein 31 (BAP31) has been reported to be involved in ER homeostasis, and plays key roles in hepatic lipid metabolism in high-fat diet-induced obese mice. However, whether BAP31 modulates hepatic lipid metabolism via regulating ER stress is still uncertain. In this study, wild-type and liver-specific BAP31-depleted mice were administrated with ER stress activator of Tunicamycin, the markers of ER stress, liver steatosis, and the underlying molecular mechanisms were determined. BAP31 deficiency increased Tunicamycin-induced hepatic lipid accumulation, aggravated liver dysfunction, and increased the mRNA levels of ER stress markers, including glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), inositol-requiring protein-1α (IRE1α) and C/EBP homologous protein (CHOP), thus promoting ER stress in vivo and in vitro. Hepatic lipid export via very low-density lipoprotein (VLDL) secretion was impaired in BAP31-depleted mice, accompanied by reduced Apolipoprotein B (APOB) and microsomal triglyceride transfer protein (MTTP) expression. Exogenous lipid clearance was also inhibited, along with impaired gene expression related to fatty acid transportation and fatty acid β-oxidation. Finally, BAP31 deficiency increased Tunicamycin-induced hepatic inflammatory response. These results demonstrate that BAP31 deficiency increased Tunicamycin-induced ER stress, impaired VLDL secretion and exogenous lipid clearance, and reduced fatty acid β-oxidation, which eventually resulted in liver steatosis.

show abstract

Section: Resultsmentioning

confidence: 99%

Induction of Liver Steatosis in BAP31-Deficient Mice Burdened with Tunicamycin-Induced Endoplasmic Reticulum Stress

Yang

Jiang

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…For example, mice on a western diet (high fat, high fructose) were partially protected from developing NAFLD if they were supplemented with combined omega-3 fatty acids with flavanols (142). Likewise, fish oil treatment was found to improve hypertriglyceridemia and insulin resistance in fructose-fed macaques, although liver fat was not assessed in that study (143).…”

Section: Modulating Factorsmentioning

confidence: 99%

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Jensen

Abdelmalek

Sullivan

et al. 2018

Journal of Hepatology

689

490

View full text Add to dashboard Cite

Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high fructose corn syrup (HFCS)) not only increases the risk for NAFLD, but also, nonalcoholic steatohepatitis (NASH). Here we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked with metabolism of fructose by fructokinase C, resulting in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations in gut permeability, microbiome, and associated endotoxemia contributes to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

show abstract

“…In this study, the intakes of total PUFA, n-6 PUFA, n-3 PUFA, and n-6/n-3 PUFA intake ratio did not affect the prevalence of hypo-HDL-cholesterolemia, even though dietary n-3 PUFA has been known to have a beneficial effect on lipid profiles and CVD in previous studies [10][11][12][13][14][15]. The reason that n-3 PUFA intake showed no association with hypo-HDL-cholesterolemia in this study may be due to the low n-3 PUFA intake of the study participants.…”

Section: Discussionmentioning

confidence: 44%

“…However, this association was not observed in men with low n-3 PUFA intakes. Our findings of the effect modification of n-3 PUFA can be partly explained by the potential synergistic relationship between dietary flavonoids and n-3 PUFAs, suggested from animal studies [13][14][15]. For example, flavonoid intake was shown to promote n-3 PUFA biosynthesis [13].…”

Section: Discussionmentioning

confidence: 59%

“…Accordingly, n-3 PUFA may interact with the antioxidant or anti-inflammatory properties of flavonoids, which may have an impact on the association between flavonoids and HDL-cholesterol. In fact, in animal studies, the intake of total flavonoids or PUFAs improved each other's bioavailability [13][14][15]. However, few human studies have investigated the effect of PUFA intake on the association between flavonoid intake and HDL-cholesterol levels.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association of Total Flavonoid Intake with Hypo-HDL-Cholesterolemia among Korean Adults: Effect Modification by Polyunsaturated Fatty Acid Intake

2020

View full text Add to dashboard Cite

The aim of this study was to examine the independent association between flavonoid intake and hypo-high-density lipoprotein (HDL)-cholesterolemia and the potential modifying effect of polyunsaturated fatty acid (PUFA) intake on this association among Korean adults. This cross-sectional analysis used data from 10,326 subjects who participated in the 2013–2016 Korean National Health and Nutrition Examination Survey. Multiple logistic regression analyses were used to assess the associations of flavonoid and PUFA intakes with hypo-HDL-cholesterolemia prevalence. Proanthocyanidins intake showed an inverse relationship with hypo-HDL-cholesterolemia only in men (Tertile (T) 3 vs. T1: odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.59–0.92, p-trend = 0.0330). Total flavonoid and PUFA intakes were not associated with hypo-HDL-cholesterolemia in both men and women. However, when stratified by PUFA intake, there was an inverse relationship between total flavonoid intake and hypo-HDL-cholesterolemia prevalence in men with a high n-3 PUFA intake (total flavonoid intakes T3 vs. T1: OR = 0.59, 95% CI = 0.42–0.82, p-trend = 0.0004) or a low n-6/n-3 PUFA intake ratio (T3 vs. T1: OR = 0.67, 95% CI = 0.48–0.93, p-trend = 0.0053), but not in those with a low n-3 PUFA intake (p-interaction = 0.0038) or a high n-6/n-3 PUFA intake ratio (p-interaction = 0.1772). In women, no association was found between total flavonoid intake and hypo-HDL-cholesterolemia, regardless of PUFA intake. These results imply that the intake of proanthocyanidins might have beneficial effects on the HDL-cholesterol level in Korean men. In addition, n-3 PUFA intake might modify the association of total flavonoid intake with the hypo-HDL-cholesterolemia among Korean men.

show abstract

n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD

Cited by 26 publications

References 50 publications

Induction of Liver Steatosis in BAP31-Deficient Mice Burdened with Tunicamycin-Induced Endoplasmic Reticulum Stress

Induction of Liver Steatosis in BAP31-Deficient Mice Burdened with Tunicamycin-Induced Endoplasmic Reticulum Stress

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Association of Total Flavonoid Intake with Hypo-HDL-Cholesterolemia among Korean Adults: Effect Modification by Polyunsaturated Fatty Acid Intake

Contact Info

Product

Resources

About