Background and Aim: Studies have shown monounsaturated oleic acid to be less toxic than palmitic acid and to prevent/attenuate palmitic acid hepatocites toxicity in steatosis models in vitro. ...However, to what degree these effects are mediated by steatosis extent is unknown.
Methods: We evaluated whether steatosis per se is associated with hepatocytes apoptosis and determined the role of oleic and palmitic acid, the most abundant fatty acids in western diets, on triglyceride accumulation and apoptosis in an in vitro model of steatosis induced in three hepatocytic cell lines (HepG2, HuH7, WRL68). The impact of incubation for 24 h with oleic (0.66 and 1.32 mM) and palmitic acid (0.33 and 0.66 mM), alone or combined (molar ratio 2 : 1) on steatosis, apoptosis, and insulin signalling, was evaluated.
Results: Concurrent with PPARγ and SREBP‐1 gene activation, steatosis extent was larger when cells were treated with oleic than with palmitic acid; the latter fatty acid was associated with increased PPARα expression. Cell apoptosis was inversely proportional to steatosis deposition. Moreover, palmitic, but not oleic acid, impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid.
Conclusions: Oleic acid is more steatogenic but less apoptotic than palmitic acid in hepatocityc cell cultures. These data may provide a biological basis for clinical findings on dietary patterns and pathogenetic models of nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV)-related liver disease are common in the general population, but their concurrence is 2- to 3-fold higher than would be expected by ...chance alone. In patients with chronic HCV infection, steatosis is attributable to a variable combination of the mechanisms considered to play a role in the pathogenesis of NAFLD—insulin resistance in the obese and in the lean subject—along with a direct effect of HCV on hepatic lipid metabolism that leads to triglyceride accumulation through inhibition of export proteins that are required for very low density lipoprotein (VLDL) assembly and secretion. Accumulating evidence suggests that steatosis contributes to the progression of fibrosis in HCV-related disease in a pattern similar to that observed in NAFLD. Potential mechanisms of this effect include the increased sensitivity of steatotic livers to oxidative stress and cytokine-mediated injury. Steatosis-related hepatic insulin resistance may also play a role through the profibrogenic effects of the compensatory hyperinsulinemia and provides a potential explanation for the association between HCV and type 2 diabetes mellitus. Indeed, an appreciation of the importance of fat in HCV has recently led to trials of adjuvant therapy for HCV directed at steatosis-associated disease mechanisms, with encouraging results reported for various modalities, including weight loss and antioxidants. Future therapy should be aimed at exploiting the interactions of HCV with host insulin and lipid metabolism, particularly in nonresponders to standard antiviral schedules.
To ascertain whether the etiology of hepatic steatosis modulates insulin resistance (IR) and to determine the predictors of IR.
We studied IR through HOMA IR in 146 subjects, 99 of whom had ...ultrasonographic and/or histologic steatosis. Twenty-two had familial heterozygous hypobetalipoproteinemia (FHBL), 48 had non-alcoholic fatty liver disease (NAFLD), 34 HCV infection (17 with HCV1b, 17 with HCV3a) and 42 were healthy controls without steatosis.
Steatosis was present in 77.3% of FHBL and, by enrolment criteria, in all NAFLD and HCV cases. Overall HOMA-IR correlated with BMI and GGT (P<0.01). FHBL and healthy groups had similar HOMA-IR and GGT values, whereas higher levels were observed in HCV and NAFLD. HCV3a and FHBL patients were hypolipidemic. HOMA-IR was similar in FHBL patients and controls and lower than in HCV and NAFLD. FHBL patients had a high extent of steatosis, similar to that observed in HCV3a, but lower grading and staging than NAFLD and HCV. At multivariate analysis, steatosis and GGT predicted HOMA-IR.
Data suggest that not all hepatic fat associates with IR. FHBL patients, for some aspects, resemble HCV3a infection, possibly suggesting a shared steatogenic mechanism. Among steatotic patients serum GGT levels is the independent predictor of IR.
Fatty liver, carotid disease and gallstones： A study of age-related associations Amedeo Lonardo Silvia Lombardini Federica Scaglioni Stefano Ballestri, Anna Maria Verrone, Marco Bertolotti Federica Scaglioni Stefano Ballestri Anna Maria Verrone Marco Bertolotti Lucia Carulli Dorval Ganazzi Nicola Carulli Paola Loria
World journal of gastroenterology,
09/2006, Letnik:
12, Številka:
36
Journal Article
Odprti dostop
AIM： To evaluate carotid intima-media thickening （IMT） and plaques, gallstone disease （GD） and fatty liver （FL） as a function of age.METHODS： In 449 subjects, FL and carotid disease were assessed ...ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease （NAFLD）, carotid disease, GD and associated factors were determined.RESULTS： FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD. Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings.CONCLUSION： Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.
Eighty-four consecutive subjects with nonalcoholic fatty liver disease (NAFLD) were tested for non-organ-specific autoantibodies (NOSA) by indirect immunoflorescence. Indices of insulin resistance ...and biochemical and anthropometric parameters were assessed. The overall prevalence of anti-nuclear-antibodies (ANA), smooth muscle antibodies (SMA) and anti-mitochondrial-antibodies (AMA) was 35.7% (30/84), 18 subjects (21.4%) being positive for ANA, 4 (4.7%) for SMA, 6 for ANA and SMA, and 2 for AMA. NOSA-positive subjects were older (P < 0.01) and mostly females (63.3%). No significant difference was found in the age-corrected parameters studied, except for copper and ceruloplasmin, which was more elevated in NOSA-positive patients. The subset of high titer (>1:100) ANA-positive patients had significantly (P < 0.05) greater insulin resistance than ANA-negative patients. In contrast, SMA-positive patients had higher gammaglobulin and significantly lower insulin resistance as compared to high-titer ANA-positive patients. In 3 NOSA-positive but not in NOSA-negative patients, liver biopsy disclosed features of overlapping NASH with autoimmune hepatitis, partially responding to diet combined with steroid treatment. In conclusion, NOSA positivity in NAFLD is more prevalent than in the general population. High-titre ANA but not SMA positivity is associated with insulin resistance.
Abstract Background Non-alcoholic fatty liver disease, one of the most prevalent liver disorders in Western countries, is characterized by hepatic accumulation of triglycerides. Bile acids have long ...been known to affect triglyceride homeostasis through a not completely understood mechanism. Aim To analyse the effects of two different manipulations of bile acid circulation on non-alcoholic fatty liver disease. Methods Two animal models of non-alcoholic fatty liver disease were developed by either feeding rats with a choline deficient or with a high fat diet. After 4 weeks, rats were randomized to undergo either bile duct ligation, sham operation or cholic acid administration. Results During cholestasis there was an increased CYP7A1 expression, the rate limiting enzyme in bile acid synthesis, and a reduction of hepatic concentration of oxysterols, ligands of the liver X receptors. Target genes of the liver X receptors, involved in fatty acid and triglyceride synthesis, were down-regulated in association with decreased hepatic triglyceride content and improvement of fatty liver. Administration of cholic acid, ligand of farnesoid X receptor, also had a beneficial effect on fatty liver in rats on choline deficient diet. Conclusion These results indicate that pharmacological approaches increasing the expression of CYP7A1 or stimulating farnesoid X receptor pathway could represent a promising treatment for non-alcoholic fatty liver disease.
To evaluate the influence of familiality on the prevalence of gallstone disease (GD) in Italy.
Families of 79 subjects with gallstones (cases) and of 79 subjects without gallstones (controls) were ...investigated for the presence of gallstones by ultrasonography. Index cases and index controls were matched for age, sex, and operative unit. Sixty-three and sixty-two husbands and wives of index cases and index controls, respectively, were also studied.
Overall, the prevalence of GD was significantly higher (c2=14.52, P<0.001) in the 202 first-degree relatives of subjects with gallstones than that in the 201 first-degree relatives of subjects without gallstones (28.6% vs 12.4%, relative risk (RR) 1.80, 95% confidence interval (CI) 1.29-2.63). In particular, prevalence of GD was significantly higher in mothers, fathers, and sisters of index cases than that in the respective family members of index controls. The highest RR was observed in mothers (RR=2.35, 95%CI 1.38-4.3). Prevalence of GD was not obviously different in brothers and also in husbands and wives of index cases and index controls. Family members of index cases did not differ from family members of control cases with respect to the most important risk factors for gallstones (age, diabetes, BMI, and number of pregnancies) with an exception of a higher prevalence of diabetes in fathers of index controls than in fathers of index cases.
This study confirms that familiality plays a very important role in the pathogenesis of gallstones.
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