Impaired reverse cholesterol transport and hepatic steatosis contribute to pathogenesis of high fat dietinduced hyperlipidemia in murine models

Purpose: To investigate the pathogenesis of high fat diet (HFD)-induced hyperlipidemia (HLP) in mice, rats and hamsters and to comparatively evaluate their sensitivity to HFD. Methods: Mice, rats and hamsters were fed with high-fat diet formulation (HFD, n = 8) or a control diet (control, n = 8) for 4 weeks. Changes in body weight, relative liver weight, serum lipid profile, expressions of hepatic marker gene of lipid metabolism and liver morphology were observed in three hyperlipidemic models. Results: Elevated total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) levels and body weight were observed in all hyperlipidemic animals (p < 0.05), while hepatic steatosis was manifested in rat and hamster HLP models, and increased hepatic TC level was only seen (p < 0.05) in hamster HLP model. Suppression of HMG-CoA reductase and up-regulation of lipoproteinlipase were observed in all HFD groups. Hepatic gene expression of LDLR, CYP7A1, LCAT, SR-B1, and ApoA I, which are a response to reverse cholesterol transport (RCT), were inhibited by HFD in the three models. Among these models, simultaneous suppression of HMG-CR, LCAT, LDLR and SR-BI and elevated LPL were features of the hamster model. Conclusion: As the results show, impaired RCT and excessive fat accumulation are major contributors to pathogenesis of HFD-induced murine HLP. Thus, the hamster model is more appropriate for hyperlipidemia research.

Impact of weight reduction program on serum alanine aminotransferase activity and immunologic response in obese hepatitis B patients.

Background: Globally, chronic B viral hepatitis (HBV) is a major health problem. Obesity is a common problem among patients with HBV. Several studies have reported that obesity is an important risk factor that alters immune system response in individuals with no underlying cause of liver disease. However, there is a strong association between BMI and the human immune system among HBV patients. Objective: This study was to examine the correlation between body mass index, serum alanine aminotransferase activity (ALT) and immunologic response in obese hepatitis B patients. Material and methods: One hundred fifty male patients with chronic hepatitis B virus, their age ranged from 30 to 45 (38.64 ± 7.12) years and their BMI ranged from 30-35 kg/m2. All Subjects were included in two groups: The first group received weight reduction program in the form of treadmill aerobic exercises in addition to diet control whereas the second group received no therapeutic intervention. Parameters of serum alanine aminotransferase (ALT), CD3, CD4 and CD8 were quantified; Leukocyte, differential counts and body mass index (BMI) were measured before and after 3 months at the end of the study. Results: There was a 24.7%, 36.8%, 30.8%, 40.7%, 28.6%, 25.9%, 33.3% and 14.3 % reduction in mean values of alanine aminotransferase (ALT), white blood cells, total neutrophil count, monocytes, CD3, CD4 ,CD8 and BMI respectively in group (A) at the end of the study. In addition, there were significant differences between mean levels of the investigated parameters in groups. Conclusion: Based on our findings, weight loss modulates serum alanine aminotransferase and immune system parameters of patients with hepatitis B virus infection.

Biochemical parameters response to weight loss in patients with non-alcoholic steatohepatitis.

Background: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Non-alcoholic steatohepatitis (NASH) is a growing public health problem with no approved therapy. NASH projected to be the leading cause of liver transplantation in the United States by 2020. Obesity, non-insulin-dependent diabetes mellitus and hyperlipidaemia are the most common associations of the disease. Global prevalence of NASH is 10-24% amongst general population but increases to 25-75% in obese diabetic individuals. Objective: There is an urgent need for efficient therapeutic options as there is still no approved medication. The aim of this study was to detect changes in biochemical parameters including insulin resistance, cytokines, blood lipid profile and liver enzymes following weight loss in patients with non-alcoholic steatohepatitis. Materials and methods: One hundred obese patients with NASH, their age between 35-50 years, body mass index (BMI) from 30 to 35 Kg/m2 were included in the study in two subgroups; the first group (A) received moderate aerobic exercise training in addition to diet regimen , where the second group (B) received no treatment intervention. Results: The mean values of leptin, TNF-α, IL6, IL8, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Homeostasis Model Assessment-Insulin Resistance- index (HOMA-IR), Total Cholesterol (TC), Low Density Lipoprotein Cholesterol (LDL-c) , Triglycerides (TG) and BMI were significantly decreased in group (A), where the mean value of Adiponectin and High Density Lipoprotein Cholesterol (HDL-c) were significantly increased, while there were no significant changes in group (B). Also, there was a significant difference between both groups at the end of the study. Conclusion: Weight loss modulates insulin resistance, adiponectin, leptin, inflammatory cytokine levels and markers of hepatic function in patients with nonalcoholic steatohepatitis.

Use of BARD scoring system in non-alcoholic fatty liver disease patients and its correlation with ultrasonographic grading in Gizan, Saudi Arabia

Purpose: To assess the efficacy of the BARD scoring system in Saudi non‐alcoholic fatty liver disease (NAFLD) patients attending Gizan General Hospital and to identify the clinical variables associated with advanced fibrosis. . Methods: The cross-sectional study involved 120 patients aged ≥ 18 years who attended the Ultrasound Department of Gizan General Hospital, Gizan, Saudi Arabia, during January – June 2013. BARD scoring system comprised the following variables: body mass index (BMI) ≥ 28 = 1 point, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio ≥ 0.8 = 2 points, and type 2 diabetes mellitus = 1 point. Results: Patients with advanced fibrosis were older (55.0 years) than patients with no/mild fibrosis (48.6 years), albeit not significantly so. A higher BMI was associated with advanced fibrosis in males, females and all study participants (p = 0.013, 0.016 and 0.001, respectively). Advanced fibrosis was more common in older patients with a higher weight to height ratio. Logistic regression suggested that age ≥ 50 years was associated with a 2.52-fold increase in the risk of advanced fibrosis, but this did not have a significant clinical impact (p = 0.087). BMI > 28 was associated with a 26.73-fold increased risk of advanced fibrosis, while AST/ALT ≥ 0.8 was associated with an 18.46-fold increased risk of advanced liver fibrosis (p = 0.002 and 0.006, respectively). Conclusion: The major risk factors for advanced fibrosis using BARD scoring system in patients with NAFLD were old age, BMI > 28, and AST/ALT ≥ 0.8. In addition, grade 3 ultrasonographic fatty liver significantly correlated with advanced fibrosis.