阿托伐他汀改善自发性高血压大鼠的心肌脂质代谢和抑制心肌肥厚

目的通过研究阿托伐他汀对自发性高血压大鼠(SHR)心肌中PPARα、CPTⅠ表达和心肌脂质代谢变化及心肌肥厚指标的影响,探讨阿托伐他汀对SHR心肌肥厚的改善作用及其机理。方法观察阿托伐他汀灌胃10周的SHR心肌肥厚指标、血清和心肌游离脂肪酸含量及心肌PPARα、CPTⅠmRNA表达的改变。结果与WKY(n=6)比较,SHR(n=6)心肌中PPARαmRNA(0.285±0.062比WKY:0.478±0.093,P<0.01)与CPTⅠmRNA(0.795±0.139比WKY:1.115±0.109,P<0.01)表达减少,血清及心肌中游离脂肪酸含量增加,分别为[(798.2±38.0比WKY:354.7±27.7)nmol/L,P<0.01]和[(635.0±77.4比WKY:245.3±47.3)nmol/L,P<0.01],心室质量指数增加(VWI)[(3.16±0.08比WKY:2.99±0.10)g/kg,P<0.05],心肌细胞直径增加(TDM)[(21.3±1.3比WKY:18.18±0.75)μm,P<0.01];阿托伐他汀50mg/kg·d治疗10周后(n=6),心肌中PPARα、CPTⅠmRNA表达增加,心肌中游离脂肪酸含量明显降低、VWI降低,TDM降低。结论阿托伐他汀能够增加心肌中PPARα、CPTⅠmRNA表达,降低心肌中游离脂肪酸含量,改善心肌脂质代谢障碍,可能是其抑制心肌肥厚发生与发展的机制之一。     

Comparative redox status in alcoholic liver disease and nonalcoholic fatty liver disease

Purpose Altered redox status has been implicated in pathogenesis of alcoholic liver disease (ALD) as well as in nonalcoholic fatty liver disease (NAFLD). This study was planned to find the relative role of redox status in these two diseases. Methods A total of 44 patients with ALD and 32 patients with NAFLD and 25 apparently healthy controls were included in the study. Redox status was estimated by measuring oxidative stress (superoxide dismutase (SOD) and lipid peroxidation products as thiobarbituric acid reactive substances (TBARS)) and antioxidant status (ferric reducing ability of plasma (FRAP) and vitamin C). Results TBARS level was raised significantly in both ALD (3.5 (2.3–9.4) vs. 1.8 (0.5–4.1) nmol/ml; P = 0.0001) and NAFLD (5.1 (1–10.2) vs. 1.82 (0.51–4.1) nmol/ml; P = 0.0001) as compared with controls, but was not different between ALD and NAFLD. SOD was significantly higher in ALD as compared to NAFLD (2.4 (1.3–7.8) vs. 0.68 (0.05–19.1) U/ml; P = 0.0001) and controls (1.12 (0.01–3.5) U/ml; P = 0.001). FRAP was lower in ALD as compared with NAFLD (345.4 (56–615.9) vs. 434.1 (197.6–733.3) μmol of Fe⁺² liberated; P = 0.001) but similar to that of controls (340.9 (141.5–697.5) μmol of Fe⁺² liberated). Conclusions ALD patients have a higher degree of redox imbalance as compared with NAFLD patients     

Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosis

Obesity is a principal risk factor for type 2 diabetes, and elevated fatty acids reduce beta-cell function and survival. An unbiased proteomic screen was used to identify targets of palmitate in beta-cell death. The most significantly altered protein in both human islets and MIN6 beta-cells treated with palmitate was carboxypeptidase E (CPE). Palmitate reduced CPE protein levels within 2 h, preceding endoplasmic reticulum (ER) stress and cell death, by a mechanism involving CPE translocation to Golgi and lysosomal degradation. Palmitate metabolism and Ca(2+) flux were also required for CPE proteolysis and beta-cell death. Chronic palmitate exposure increased the ratio of proinsulin to insulin. CPE null islets had increased apoptosis in vivo and in vitro. Reducing CPE by approximately 30% using shRNA also increased ER stress and apoptosis. Conversely, overexpression of CPE partially rescued beta-cells from palmitate-induced ER stress and apoptosis. Thus, carboxypeptidase E degradation contributes to palmitate-induced beta-cell ER stress and apoptosis. CPE is a major link between hyperlipidemia and beta-cell death pathways in diabetes.     

Non-alcoholic fatty liver disease--a common and benign finding in octogenarian patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a common entity in the general population, has been shown to be linked with insulin resistance and metabolic syndrome. Several of the components of the metabolic syndrome are more common in the aged population. The aims of the current study were to determine in the aged, the prevalence and the clinical presentation of NAFLD, as well as the relation to the underlying metabolic abnormalities. METHOD: In this prospective study, we evaluated 91 octogenarians with a mean age of 85.56+/-3.76 years, who were admitted to the rehabilitation departments of a geriatric hospital. Clinical evaluation included: abdominal ultrasound (US), fasting glucose and lipid levels, serum liver enzymes, ferritin, iron and transferrin saturation. Elderly patients with NAFLD were compared with 46 young patients with NAFLD. RESULTS: NAFLD diagnosed by US was a common finding in this aged population, is present in 42/91 patients (46.2%). No significant differences were observed between the patients with or without NAFLD in the following: age, gender, chronic illnesses, anthropometric parameters, lipid profile, fasting glucose levels, metabolic syndrome prevalence, serum levels of transaminases, ferritin and iron. Young patients with NAFLD had significantly higher serum levels of triglycerides and a significantly higher prevalence of glucose intolerance, obesity and the metabolic syndrome compared with the elderly patients with NAFLD. CONCLUSIONS: NAFLD was a common finding in our group of elderly patients and the prevalence was higher than reported in the general population. In contrast to the well-described association between the metabolic syndrome and NAFLD in the general population, we did not find this association in the aged group. In addition, none of the patients had stigmata of advanced liver disease. These data suggest that NAFLD is a common and benign finding in the elderly population, but is not associated with the metabolic syndrome.     

IL-18 and IL-12 induce intestinal inflammation and fatty liver in mice in an IFN-gamma dependent manner

BACKGROUND: In murine models of inflammatory bowel disease, colonic inflammation is considered to be caused by an aberrant Th1-type immune response. AIM: To investigate if systemic administration of interleukin (IL)-12 and IL-18 to wild-type BALB/c mice induces liver injury and intestinal inflammation, and if pathological changes are observed, what cytokines are involved. METHODS: Mice (BALB/c-wild-type (wt), MRL-lpr/lpr, BALB/c-interferon gamma knock out (IFN-gamma KO), C57BL/6-inducible nitric oxide synthase (iNOS) KO, and BALB/c tumour necrosis factor alpha (TNF-alpha) KO) were injected intraperitoneally each day with IL-12 (20 ng/g/mouse) and/or IL-18 (200 ng/g/mouse). RESULTS: Administration of IL-12 and IL-18 to BALB/c-wt mice induced prominent intestinal mucosal inflammation and fatty liver, leading to piloerection, bloody diarrhoea, and weight loss. IL-12 and IL-18 induced striking elevations in serum levels of IFN-gamma that caused NO production, although increased NO had no exacerbating effect on mice. Moreover, iNOS KO mice, or MRL lpr/lpr mice lacking functional Fas were equally susceptible to IL-12 and IL-18. Administration of IL-12 and IL-18 did not induce TNF-alpha production in wild-type mice, and the same treatment to TNF-alpha KO mice induced intestinal mucosal inflammation. Furthermore, they had diffuse and dense infiltration of small fat droplets in their hepatocytes associated with an increase in serum levels of liver enzymes. In contrast, the same treatment in IFN-gamma KO BALB/c mice and iNOS KO mice did not induce these changes. CONCLUSIONS: Our study strongly indicates that IL-18 together with IL-12 induces intestinal mucosal inflammation in an IFN-gamma dependent but TNF-alpha, NO, and Fas ligand independent manner, and fatty liver is dependent on IFN-gamma and NO.     

Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure

BACKGROUND: An adequate energy-protein intake (EPI) when combined with amino acid supplementation may have a positive impact on nutritional and metabolic status in patients with chronic heart failure (CHF). METHODS AND RESULTS: Thirty eight stable CHF patients (27 males, 73.5+/-4 years; BMI 22.5+/-1.4 kg/m2), with severe depletion of muscle mass and were randomised to oral supplements of essential amino acids 8 g/day (EAA group; n=21) or no supplements (controls; n=17). All patients had adequate EPI (energy> or =30 kcal/kg; proteins >1.1 g/kg). At baseline and 2-months after randomisation, the patients underwent metabolic (plasma lactate, pyruvate concentration; serum insulin level; estimate of insulin resistance by HOMA index), nutritional (measure of nitrogen balance), and functional (exercise test, walking test) evaluations. Body weight increased by >1 kg in 80% of supplemented patients (mean 2.96 kg) and in 30% of controls (mean 2.3 kg) (interaction <0.05). Changes in arm muscle area, nitrogen balance, and HOMA index were similar between the two treatment groups. Plasma lactate and pyruvate levels increased in controls (p<0.01 for both) but decreased in the supplemented group (p<0.01 and 0.02 respectively). EAA supplemented patients but not controls improved both exercise output and peak oxygen consumption and walking test. CONCLUSIONS: Adequate EPI when combined with essential amino acid supplementation may improve nutritional and metabolic status in most muscle-depleted CHF patients.     

Metabolic syndrome and associated factors among psychiatric patients in Jimma University Specialized Hospital,South West Ethiopia

Background

Metabolic syndrome is a multisystem disorder which coined to describe the recognized clustering of metabolic and cardiovascular abnormalities including obesity, hypertension, dyslipidemia, and abnormalities of glucose homeostasis.

非酒精性脂肪性肝病分级分期管理研究进展

非酒精性脂肪性肝病（NAFLD）是代谢综合征在肝脏的病理学表现。由于饮食结构的改变,NAFLD发病率呈现上升趋势,且NAFLD与肝病进展、糖尿病和心血管疾病死亡密切相关。因此,寻求NAFLD患者综合管理方法迫在眉睫。本文综述了NAFLD分级、分期、治疗和随访评估的研究进展,以期指导临床诊断、治疗和管理。