scholarly journals A Low ω-6 to ω-3 PUFA Ratio (n–6:n–3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth

2020 ◽  
Vol 150 (9) ◽  
pp. 2314-2321 ◽  
Author(s):  
Michelle A Van Name ◽  
Mary Savoye ◽  
Jennifer M Chick ◽  
Brittany T Galuppo ◽  
Ariel E Feldstein ◽  
...  
Keyword(s):  
At Risk ◽  
Liver Disease ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Pufa Ratio ◽  
Obese Youth ◽  
Pufa Diet

ABSTRACT Background Recent literature suggests that the Western diet's imbalance between high ω-6 (n–6) and low ω-3 (n–3) PUFA intake contributes to fatty liver disease in obese youth. Objectives We tested whether 12 wk of a low n–6:n–3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response. Methods In a single-arm unblinded study, obese youth 9–19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n–6:n–3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann–Whitney U test, and covariance pattern modeling were used. Results Twenty obese adolescents (median age: 13.3 y; IQR: 10.5–16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time. Conclusions These data suggest that, independently of weight loss, a low n–6:n–3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype. This trial was registered at clinicaltrials.gov as NCT01556113.

scholarly journals Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease

2012 ◽  
Vol 113 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Ciaran E. Fealy ◽  
Jacob M. Haus ◽  
Thomas P. J. Solomon ◽  
Mangesh Pagadala ◽  
Chris A. Flask ◽  
...  
Keyword(s):  
Liver Disease ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Fat Oxidation ◽  
Whole Body ◽  
Hepatocyte Apoptosis ◽  
Short Term ◽  
Nonalcoholic Fatty Liver

Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis—plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)—in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m2, >5% intrahepatic lipid (IHL) assessed by 1H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ∼85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (V̇o2max) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = −0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.

Ethnicity and Common Genetic Variants Modulate Nonalcoholic Fatty Liver Disease (NAFLD) Metabolic Phenotype in Obese Youth

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 313-OR
Author(s):  
DOMENICO TRICO ◽  
SONIA CAPRIO ◽  
GIUSEPPINA R. UMANO ◽  
ALFONSO GALDERISI ◽  
MARIANA M. MATA ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Genetic Variants ◽  
Fatty Liver Disease ◽  
Metabolic Phenotype ◽  
Nonalcoholic Fatty Liver ◽  
Obese Youth ◽  
Common Genetic Variants

scholarly journals The Impact of Nordic Walking on Bone Properties in Postmenopausal Women with Pre-Diabetes and Non-Alcohol Fatty Liver Disease

2021 ◽  
Vol 18 (14) ◽  
pp. 7570
Author(s):  
Xiaming Du ◽  
Chao Zhang ◽  
Xiangqi Zhang ◽  
Zhen Qi ◽  
Sulin Cheng ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Postmenopausal Women ◽  
Fatty Liver Disease ◽  
Whole Body ◽  
Nordic Walking ◽  
Significant Group ◽  
Time Interaction ◽  
Bone Properties ◽  
The Impact

This study investigated the impact of Nordic walking on bone properties in postmenopausal women with pre-diabetes and non-alcohol fatty liver disease (NAFLD). A total of 63 eligible women randomly participated in the Nordic walking training (AEx, n = 33), or maintained their daily lifestyle (Con, n = 30) during intervention. Bone mineral content (BMC) and density (BMD) of whole body (WB), total femur (TF), femoral neck (FN), and lumbar spine (L2-4) were assessed by dual-energy X-ray absorptiometry. Serum osteocalcin, pentosidine, receptor activator of nuclear factor kappa-B ligand (RANKL) levels were analyzed by ELISA assay. After an 8.6-month intervention, the AEx group maintained their BMCTF, BMDTF, BMCL2−4, and BMDL2−4, and increased their BMCFN (p = 0.016), while the Con group decreased their BMCTF (p = 0.008), BMDTF (p = 0.001), and BMDL2−4 (p = 0.002). However, no significant group × time interaction was observed, except for BMDL2−4 (p = 0.013). Decreased pentosidine was correlated with increased BMCWB(r = −0.352, p = 0.019). The intervention has no significant effect on osteocalcin and RANKL. Changing of bone mass was associated with changing of pentosidine, but not with osteocalcin and RANKL. Our results suggest that Nordic walking is effective in preventing bone loss among postmenopausal women with pre-diabetes and NAFLD.

scholarly journals Sex Dimorphism of Nonalcoholic Fatty Liver Disease (NAFLD) in Pparg-Null Mice

2021 ◽  
Vol 22 (18) ◽  
pp. 9969
Author(s):  
Mariano Schiffrin ◽  
Carine Winkler ◽  
Laure Quignodon ◽  
Aurélien Naldi ◽  
Martin Trötzmüller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Whole Body ◽  
Sex Dimorphism ◽  
Nonalcoholic Fatty Liver

Men with nonalcoholic fatty liver disease (NAFLD) are more exposed to nonalcoholic steatohepatitis (NASH) and liver fibrosis than women. However, the underlying molecular mechanisms of NALFD sex dimorphism are unclear. We combined gene expression, histological and lipidomic analyses to systematically compare male and female liver steatosis. We characterized hepatosteatosis in three independent mouse models of NAFLD, ob/ob and lipodystrophic fat-specific (PpargFΔ/Δ) and whole-body PPARγ-null (PpargΔ/Δ) mice. We identified a clear sex dimorphism occurring only in PpargΔ/Δ mice, with females showing macro- and microvesicular hepatosteatosis throughout their entire life, while males had fewer lipid droplets starting from 20 weeks. This sex dimorphism in hepatosteatosis was lost in gonadectomized PpargΔ/Δ mice. Lipidomics revealed hepatic accumulation of short and highly saturated TGs in females, while TGs were enriched in long and unsaturated hydrocarbon chains in males. Strikingly, sex-biased genes were particularly perturbed in both sexes, affecting lipid metabolism, drug metabolism, inflammatory and cellular stress response pathways. Most importantly, we found that the expression of key sex-biased genes was severely affected in all the NAFLD models we tested. Thus, hepatosteatosis strongly affects hepatic sex-biased gene expression. With NAFLD increasing in prevalence, this emphasizes the urgent need to specifically address the consequences of this deregulation in humans.

Evaluation of Predictive Factors in Patients with Nonalcoholic Fatty Liver Disease after Pancreaticoduodenectomy

2014 ◽  
Vol 80 (5) ◽  
pp. 500-504 ◽  
Author(s):  
Yasuhiro Ito ◽  
Takeshi Kenmochi ◽  
Shintaro Shibutani ◽  
Tomohisa Egawa ◽  
Shinobu Hayashi ◽  
...  
Keyword(s):  
At Risk ◽  
Risk Factor ◽  
Liver Disease ◽  
Blood Loss ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Pancreatic Head ◽  
Nonalcoholic Fatty Liver ◽  
Endocrine Insufficiency

Patients who undergo pancreaticoduodenectomy (PD) are at risk of steatosis because resection of the pancreatic head causes pancreatic exocrine and endocrine insufficiency. We investigated the clinicopathological features and the risk factors of nonalcoholic fatty liver disease (NAFLD) after PD. This was a retrospective study of 100 patients who underwent PD between April 2007 and December 2012 in our institution. Preoperative demographic and clinical data, surgical procedures, pathological diagnosis, postoperative course findings, and complication details were collected prospectively. The patients were divided into the following two groups: Group A consisted of 12 patients who developed postoperative NAFLD, and Group B consisted of 88 patients who did not develop postoperative NAFLD. Pancreatic carcinoma and pancreatic texture showed similar findings. Additionally, we found that blood loss significantly correlated with the incidence of nonalcoholic steatohepatitis after PD. In multivariate analysis, only blood loss was identified as the most influential risk factor for NAFLD (hazard ratio, 1.0001; P = 0.016). Blood loss was identified as an independent risk factor for the development of NAFLD after PD. Further prospective studies are needed to identify factors that put patients at risk for NAFLD after PD. Continuing efforts should be made to improve patient outcomes and understand the pathogenesis of postpancreatectomy NASH.

scholarly journals Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats

2016 ◽  
Vol 113 (13) ◽  
pp. E1796-E1805 ◽  
Author(s):  
Geraldine Harriman ◽  
Jeremy Greenwood ◽  
Sathesh Bhat ◽  
Xinyi Huang ◽  
Ruiying Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthesis ◽  
Fatty Liver Disease ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase

Simultaneous inhibition of the acetyl-CoA carboxylase (ACC) isozymes ACC1 and ACC2 results in concomitant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation and may favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver disease. Using structure-based drug design, we have identified a series of potent allosteric protein–protein interaction inhibitors, exemplified by ND-630, that interact within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit the enzymatic activity of both ACC isozymes, reduce fatty acid synthesis and stimulate fatty acid oxidation in cultured cells and in animals, and exhibit favorable drug-like properties. When administered chronically to rats with diet-induced obesity, ND-630 reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. When administered chronically to Zucker diabetic fatty rats, ND-630 reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). Together, these data suggest that ACC inhibition by representatives of this series may be useful in treating a variety of metabolic disorders, including metabolic syndrome, type 2 diabetes mellitus, and fatty liver disease.

Rat liver epigenome programing by perinatal exposure to 2,2′,4′4′-tetrabromodiphenyl ether

Epigenomics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 235-249 ◽  
Author(s):  
Alexander Suvorov ◽  
Vladimir Naumov ◽  
Victoria Shtratnikova ◽  
Maria Logacheva ◽  
Alex Shershebnev ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Polybrominated Diphenyl Ethers ◽  
Fatty Liver Disease ◽  
Diphenyl Ether ◽  
Metabolic Phenotype ◽  
Perinatal Exposure ◽  
Adult Rats ◽  
Nonalcoholic Fatty Liver

Perinatal exposures to polybrominated diphenyl ethers permanently reprogram liver metabolism and induce a nonalcoholic fatty liver disease-like phenotype and insulin resistance in rodents. Aim: To test if these changes are associated with altered liver epigenome. Materials & methods: Expression of small RNA and changes in DNA methylation in livers of adult rats were analyzed following perinatal exposure to 2,2′,4,4′-tetrabromodiphenyl ether, the polybrominated diphenyl ether congener most prevalent in human tissues. Results: We identified 33 differentially methylated DNA regions and 15 differentially expressed miRNAs. These changes were enriched for terms related to lipid and carbohydrate metabolism, insulin signaling, Type-2 diabetes and nonalcoholic fatty liver disease. Conclusion: Changes in the liver epigenome are a likely candidate mechanism of long-term maintenance of an aberrant metabolic phenotype.

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