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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim was to examine the role of cyclooxygenase (COX)-2-mediated inflammation in the development of obese linked insulin resistance and fatty liver. The rats were fed separately regular diet (CONT), high-fat diet (HFD) ad libitum, or energy restrictedly for 12 weeks. Rats fed HFD ad libitum were further divided into three subgroups co-treated with vehicle (HFa), or a selective COX-2 inhibitor celecoxib (HFa-Cel) or mesulid (HFa-Mes). Euglycemic hyperinsulinemic clamp (EHC) experiment was performed at the end of study. Another set of rats with similar grouping was further divided into those with a 4, 8, or 12-week intervention period for hepatic sampling. Body weight was increased significantly and similarly in HFa, HFa-Cel, and HFa-Mes. Time-dependent increases in plasma insulin, glucose, 8-isoprostanes, leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and hepatic triglyceride contents shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. During EHC period, the reduction in stimulation of whole body glucose uptake, suppression of hepatic glucose production and metabolic clearance rate of insulin shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The enhanced COX-2 and tumor necrosis factor-alpha (TNF-alpha) but attenuated PPAR-gamma and C/EBP-alpha mRNA expressions in epididymal fat shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The increases in average cell size of adipocytes and CD68 positive cells shown in HFa were also significantly reversed in HFa-Cel and HFa-Mes. Our findings suggest that COX-2 activation in fat inflammation is important in the development of insulin resistance and fatty liver in high fat induced obese rats.
Obesity (Silver Spring) 2009 Jun
PMID:COX-2-mediated inflammation in fat is crucial for obesity-linked insulin resistance and fatty liver. 1924 74

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance. It is also a predisposing factor for type 2 diabetes. Dietary factors are believed to contribute to all three diseases. NAFLD is characterized by increased intrahepatic fat and mitochondrial dysfunction, and its etiology may be attributed to excessive fructose intake. Consumption of high fructose corn syrup-55 (HFCS-55) stands at up to 15% of the average total daily energy intake in the United States, and is linked to weight gain and obesity. The aim of this study was to establish whether HFCS-55 could contribute to the pathogenesis of NAFLD, by examining the effects of HFCS-55 on hepatocyte lipogenesis, insulin signaling, and cellular function, in vitro and in vivo. Exposure of hepatocytes to HFCS-55 caused a significant increase in hepatocellular triglyceride (TG) and lipogenic proteins. Basal production of reactive oxygen metabolite (ROM) was increased, together with a decreased capacity to respond to an oxidative challenge. HFCS-55 induced a downregulation of the insulin signaling pathway, as indicated by attenuated (ser473)phosphorylation of AKT1. The c-Jun amino-terminal kinase (JNK), which is intimately linked to insulin resistance, was also activated; and this was accompanied by an increase in endoplasmic reticulum (ER) stress and intracellular free calcium perturbation. Hepatocytes exposed to HFCS-55 exhibited mitochondrial dysfunction and released cytochrome C (CytC) into the cytosol. Hepatic steatosis and mitochondrial disruption was induced in vivo by a diet enriched with 20% HFCS 55; accompanied by hypoadiponectinemia and elevated fasting serum insulin and retinol-binding protein-4 (RBP4) levels. Taken together our findings indicate a potential mechanism by which HFCS-55 may contribute to the pathogenesis of NAFLD.
Obesity (Silver Spring) 2009 Nov
PMID:Diabetes of the liver: the link between nonalcoholic fatty liver disease and HFCS-55. 1928 20

Although nonalcoholic fatty liver disease (NAFLD) is frequent in obesity, the metabolic determinants of advanced liver disease remain unclear. Adipokines reflect inflammation and insulin resistance associated with obesity and may identify advanced NAFLD. At the time of obesity surgery, 142 consecutive patients underwent liver biopsy and had their preoperative demographic and clinical data obtained. Liver histology was scored by the NAFLD activity score, and patients subdivided into four groups. Concentrations of retinol-binding protein 4 (RBP4), adiponectin, tumor necrosis factor-alpha (TNF-alpha), and leptin were determined approximately 1 week prior to surgery and results were related to liver histology. The prevalence of no NAFLD was 30%, simple steatosis 23%, borderline nonalcoholic steatohepatitis (NASH) 28%, and definitive NASH 18%. Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) prevalence were 39 and 75%, respectively, and did not differ across the four histological groups (P = NS). Triglyceride (TG) and alanine transaminase (ALT) levels, strongly associated with advanced stages of NAFLD and NASH (P = 0.04). TG levels >150 mg/dl, increased the likelihood of NASH 3.4-fold, whereas high-density lipoprotein (HDL) levels predicted no NAFLD (P < 0.01). Concentrations of TNF-alpha, leptin, and RBP4 did not differ among histological groups and thus did not identify NASH; however, there was a trend for adiponectin to be lower in NASH vs. no NAFLD (P = 0.061). In summary, both TG and ALT levels assist in identification of NASH in an obesity surgery cohort. These findings underscore the importance of fatty acid delivery mechanisms to NASH development in severely obese individuals.
Obesity (Silver Spring) 2009 Sep
PMID:Triglyceride levels and not adipokine concentrations are closely related to severity of nonalcoholic fatty liver disease in an obesity surgery cohort. 1936 15

To constitute a valuable resource to identify individual genes involved in the development of obesity, a novel mouse model, the Berlin Fat Mouse Inbred line 860 (BFMI860), was established. In order to characterize energy intake and energy expenditure in obese BFMI860 mice, we performed two independent sets of experiments in male BFMI860 and B6 control mice (10 per line). In experiment 1, we analyzed body fat content noninvasively by dual-energy X-ray absorptiometry and measured resting metabolic rate at thermoneutrality (RMRt) and respiratory quotient (RQ) in week 6, 10, and 18. In a second experiment, energy digested (energy intake minus fecal energy loss) was determined by bomb calorimetry from week 6 through week 12. BFMI860 mice were heavier and had higher fat mass (final body fat content was 24.7% compared with 14.6% in B6). They also showed fatty liver syndrome. High body fat accumulation in BFMI860 mice was restricted to weeks 6-10 and was accompanied by hyperphagia, higher energy digestion, higher RQs, and abnormally high blood triglyceride levels. Lean mass-adjusted RMRt was not altered between lines. These results indicate that in BFMI860 mice, the excessive accumulation of body fat is associated with altered lipid metabolism, high energy intake, and energy digestion. Assuming that BFMI860 mice and their obese phenotypes are of polygenic nature, this line is an excellent model for the study of obesity in humans, especially for juvenile obesity and hyperlipidemia.
Obesity (Silver Spring) 2009 Nov
PMID:High energy digestion efficiency and altered lipid metabolism contribute to obesity in BFMI mice. 1939 May 16

Both obesity and aging increase intrahepatic fat (IHF) content, which leads to nonalcoholic fatty liver disease (NAFLD) and metabolic abnormalities such as insulin resistance. We evaluated the effects of diet and diet in conjunction with exercise on IHF content and associated metabolic abnormalities in obese older adults. Eighteen obese (BMI >or=30 kg/m(2)) older (>or=65 years old) adults completed a 6-month clinical trial. Participants were randomized to diet (D group; n = 9) or diet + exercise (D+E group; n = 9). Primary outcome was IHF quantified by magnetic resonance spectroscopy (MRS). Secondary outcomes included insulin sensitivity (assessed by oral glucose tolerance), body composition (assessed by dual-energy X-ray absorptiometry), physical function (VO(2 peak) and strength), glucose, lipids, and blood pressure (BP). Body weight (D: -9 +/- 1%, D+E: -10 +/- 2%, both P < 0.05) and fat mass (D: -13 +/- 3%, D+E -16 +/- 3%, both P < 0.05) decreased in both groups but there was no difference between groups. IHF decreased to a similar extent in both groups (D: -46 +/- 11%, D+E: -45 +/- 8%, both P < 0.05), which was accompanied by comparable improvements in insulin sensitivity (D: 66 +/- 25%, D+E: 68 +/- 28%, both P < 0.05). The relative decreases in IHF correlated directly with relative increases in insulin sensitivity index (ISI) (r = -0.52; P < 0.05). Improvements in VO(2 peak), strength, plasma triglyceride (TG), and low-density lipoprotein-cholesterol concentration, and diastolic BP occurred in the D+E group (all P < 0.05) but not in the D group. Diet with or without exercise results in significant decreases in IHF content accompanied by considerable improvements in insulin sensitivity in obese older adults. The addition of exercise to diet therapy improves physical function and other obesity- and aging-related metabolic abnormalities.
Obesity (Silver Spring) 2009 Dec
PMID:Diet and exercise interventions reduce intrahepatic fat content and improve insulin sensitivity in obese older adults. 1939 May 17

An abundance of fat stored within the liver, or steatosis, is the beginning of a broad hepatological spectrum, usually referred to as fatty liver disease (FLD). For studies on FLD, quantitative hepatic fat ultrasonography would be an appealing study modality. Objective of this study was to develop a technique for quantifying hepatic fat content by ultrasonography and validate this using proton magnetic resonance spectroscopy ((1)H MRS) as gold standard. Eighteen white volunteers (BMI range 21.0-42.9) were scanned by both ultrasonography and (1)H MRS. Altered ultrasound characteristics, present in the case of FLD, were assessed using a specially developed software program. Various attenuation and textural based indices of FLD were extracted from ultrasound images. Using linear regression analysis, the predictive power of several models (consisting of both attenuation and textural based measures) on log 10-transformed hepatic fat content by (1)H MRS were investigated. The best quantitative model was compared with a qualitative ultrasonography method, as used in clinical care. A model with four ultrasound characteristics could modestly predict the amount of liver fat (adjusted explained variance 43.2%, P = 0.021). Expanding the model to seven ultrasound characteristics increased adjusted explained variance to 60% (P = 0.015), with r = 0.789 (P < 0.001). Comparing this quantitative model with qualitative ultrasonography revealed a significant advantage of the quantitative model in predicting hepatic fat content (P < 0.001). This validation study shows that a combination of computer-assessed ultrasound measures from routine ultrasound images can be used to quantitatively assess hepatic fat content.
Obesity (Silver Spring) 2009 Dec
PMID:Ultrasonography to quantify hepatic fat content: validation by 1H magnetic resonance spectroscopy. 1946 88

No specific treatment for nonalcoholic hepatic fatty liver disease has been defined. We followed the spontaneous evolution of liver steatosis and tested the therapeutic usefulness of metformin and fenofibrate in a model of steatosis, the Zucker diabetic fatty (ZDF) rat. ZDF and control rats were studied at 7, 14, and 21 weeks. After initial study at 7 weeks, ZDF rats received no treatment, metformin or fenofibrate until studies at 14 or 21 weeks. ZDF rats were obese, hypertriglyceridemic, insulin resistant at 7 weeks, type 2 diabetic at 14, diabetic with insulin deficiency at 21. They had steatosis at 7 weeks with increased hepatic expression and activity of lipogenesis. Steatosis was unchanged at 14 and 21 weeks despite lower expression and activity of lipogenesis. Metformin and fenofibrate did not modify energy intake or expenditure or the evolution of diabetes. Both compounds decreased plasma triacylglycerol (TAG) concentrations. Hepatic TAG content was reduced by fenofibrate at 14 and 21 weeks but only at 21 weeks by metformin. Metformin had no significant effects on the expression in liver of genes of fatty acids metabolism. The beneficial effect of fenofibrate occurred despite increased expression of genes involved in the uptake and activation of fatty acids. Acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase I (CPTI) mRNA levels were increased by fenofibrate showing evidence of increased lipid oxidation. To conclude, metformin had only moderate effects on liver steatosis. The effects of fenofibrate was more marked but remained mild.
Obesity (Silver Spring) 2009 Jul
PMID:Nonalcoholic hepatic steatosis in Zucker diabetic rats: spontaneous evolution and effects of metformin and fenofibrate. 1955 25

Dietary trans-fatty acids are associated with increased risk of cardiovascular disease and have been implicated in the incidence of obesity and type 2 diabetes mellitus (T2DM). It is established that high-fat saturated diets, relative to low-fat diets, induce adiposity and whole-body insulin resistance. Here, we test the hypothesis that markers of an obese, prediabetic state (fatty liver, visceral fat accumulation, insulin resistance) are also worsened with provision of a low-fat diet containing elaidic acid (18:1t), the predominant trans-fatty acid isomer found in the human food supply. Male 8-week-old Sprague-Dawley rats were fed a 10% trans-fatty acid enriched (LF-trans) diet for 8 weeks. At baseline, 3 and 6 weeks, in vivo magnetic resonance spectroscopy (1H-MR) assessed intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content. Euglycemic-hyperinsulinemic clamps (week 8) determined whole-body and tissue-specific insulin sensitivity followed by high-resolution ex vivo 1H-NMR to assess tissue biochemistry. Rats fed the LF-trans diet were in positive energy balance, largely explained by increased energy intake, and showed significantly increased visceral fat and liver lipid accumulation relative to the low-fat control diet. Net glycogen synthesis was also increased in the LF-trans group. A reduction in glucose disposal, independent of IMCL accumulation was observed in rats fed the LF-trans diet, whereas in rats fed a 45% saturated fat (HF-sat) diet, impaired glucose disposal corresponded to increased IMCLTA. Neither diet induced an increase in IMCLsoleus. These findings imply that trans-fatty acids may alter nutrient handling in liver, adipose tissue, and skeletal muscle and that the mechanism by which trans-fatty acids induce insulin resistance differs from diets enriched with saturated fats.
Obesity (Silver Spring) 2009 Jun
PMID:Metabolic implications of dietary trans-fatty acids. 1958 78

Obesity-induced inflammation contributes to the development of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether dietary capsaicin can reduce obesity-induced inflammation and metabolic disorders such as insulin resistance and hepatic steatosis. Male C57BL/6 obese mice fed a high-fat diet for 10 weeks received a supplement of 0.015% capsaicin for a further 10 weeks and were compared with unsupplemented controls. Glucose intolerance was estimated by glucose tolerance tests. Transcripts of adipocytokine genes and the corresponding proteins were measured by reverse transcription-PCR and enzyme-linked immunosorbent assay, and macrophage numbers were determined by flow cytometric analysis. Transient receptor potential vanilloid type-1 (TRPV-1), peroxisome proliferator-activated receptor (PPAR)-alpha, and PPARgamma coactivator-1alpha (PGC-1alpha) mRNAs were also measured by RT-PCR, and PPARalpha luciferase assays were performed. Dietary capsaicin lowered fasting glucose, insulin, leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Levels of tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-6 mRNAs and proteins in adipose tissue and liver decreased markedly, as did macrophage infiltration, hepatic triglycerides, and TRPV-1 expression in adipose tissue. At the same time, the mRNA/protein of adiponectin in the adipose tissue and PPARalpha/PGC-1alpha mRNA in the liver increased. Moreover, luciferase assays revealed that capsaicin is capable of binding PPARalpha. Our data suggest that dietary capsaicin may reduce obesity-induced glucose intolerance by not only suppressing inflammatory responses but also enhancing fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. The effects of capsaicin in adipose tissue and liver are related to its dual action on PPARalpha and TRPV-1 expression/activation.
Obesity (Silver Spring) 2010 Apr
PMID:Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. 1979 65

The ability to accurately and noninvasively quantify fatty infiltration in organs such as the liver and the pancreas remains a critical component in understanding the link between obesity and its comorbidities such as type 2 diabetes and fatty liver disease. Single-voxel ((1)H) proton magnetic resonance spectroscopy (MRS) has long been regarded as the gold-standard noninvasive technique for such measurements. Recent advances in three-dimensional fat-water magnetic resonance imaging (MRI) methods have led to the development of rapid, robust, and quantitative approaches that can accurately characterize the proportion of fat and water content in underlying tissues across the full imaging volume, and hence entire organs of interest. One such technique is called IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation). This article prospectively compares three-dimensional (3D) IDEAL-MRI and single-voxel MRS in the assessment of hepatic (HFF) and pancreatic fat fraction (PFF) in 16 healthy subjects. MRS acquisitions took 3-4 min to complete whereas IDEAL acquisitions were completed in 20-s breath-holds. In the liver, there was a strong correlation (slope = 0.90, r(2) = 0.95, P < 0.001) between IDEAL and MRS-based fat fractions. In the pancreas, a poorer agreement between IDEAL and MRS was observed (slope = 0.32, r(2) = 0.51, P < 0.02). The discrepancy of PFF is likely explained by MRS signal contamination from surrounding visceral fat, presumably during respiratory motion. We conclude that IDEAL is equally accurate in characterizing hepatic fat content as MRS, and is potentially better suited for fat quantification in smaller organs such as the pancreas.
Obesity (Silver Spring) 2010 Apr
PMID:Comparison of fat-water MRI and single-voxel MRS in the assessment of hepatic and pancreatic fat fractions in humans. 1983 63


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