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Background/Aims@#Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs). @*Methods@#Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used. @*Results@#A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated. @*Conclusions@#Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.
ABSTRACT
Objective To identify the threshold of percentage of body fat (BF％) associated with diabetes mellitus,hypertension and dyslipidemia in an elderly Chinese population.Methods An individual was considered as a subject if they exhibited any one of the three cardiovascular disease risk factors:diabetes mellitus,hypertension or dyslipidemia.A total of 1 140 subjects were recruited from the Physical Examination Center of Tianjin Hospital,China (male 511,female 629,aged ≥60 years).Questionnaire interview,physical examination,body composition measurement,blood biochemistry measurement,muscle strength measurement and other measurements were performed for each subject.Receiver operating curves (ROC) were created to determine the optimal percentage of body fat cutoff points,with the presence of diabetes mellitus,hypertension or dyslipidemia as outcome variable.Results The percentage of subjects with at least one of the following conditions (diabetes mellitus,hypertension or dyslipidemia) was 62.8％ for men and 73.9％ for women.Increased percentage of body fat was associated with an increased occurrence of diabetes mellitus,hypertension or dyslipidemia in the elderly,particularly among women.The ROC curve shows that the threshold of fat percentage in men and women was 28.2％ and 36.6％,respectively.Conclusion The risks of diabetes,hypertension and dyslipidemia is closely related to elevated body fat mass in the elderly.The percentage of body fat mass is an important indicator of obesity,threshold of BF ％ can provide reference for clinical obesity intervention in elderly patients.It also can provide reference for the treatment and prevention of cardiovascular disease.
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Objective: To explore influence of exercise training and angiotensin-converting enzyme inhibitor (perindopril) on blood pressure, aortic compliance and cardiovascular tissue structure in spontaneously hypertensive rats (SHR). Methods: A total of 38 SHR aged seven weeks were divided into control group (C group, n=9), exercise group (Exe group, n=9), perindopril group (Per group, n=10) and perindopril + exercise group (Per＋Exe group, n=10). SHRs were observed for eight weeks, and tail-cuff method was used to measure systolic blood pressure（SBP）once a week. When rats were 15 weeks old, regression line（once linear function）was obtained by single regression analyzing the relation between blood pressure and pulse wave velocity（PWV）. The b of this once linear function was used as index of aortic compliance（there was negative relationship between b and aortic compliance）. The left ventricular mass （LVM）/body weight（BW）was used to evaluate ventricular thickening, and aortic weight （AO）/ BW was regard as index of vascular thickening. Results: Compared with C group, SBP of Exe group significantly decreased on 12 weeks old (P0.05）. On 15 weeks old, the LVM/BW [(2.19±0.36) mg/g, (2.16±0.32) mg/g ] and AO/BW [(0.20±0.01) mg/g, (0.19±0.01) mg/g] of Per group and Per+ Exe group significantly decreased compared with C group [(2.95±0.58) mg/g, (0.26±0.01) mg/g], P<0.05 all, but there was no significant difference in these indexes between Per group and Per+ Exe group and between C group and Exe group（P＞0.05 both）. The b （index of aortic compliance）were [（C group ：（21.2±1.2）, Exe group：（20.5±1.4）, Per group：（14.8±1.6），Per＋Exe group：（15.0±1.3）] respectively, there was no significant difference between Per group and Per+ Exe group and between C group and Exe group（P＞0.05 both）. Conclusion: The exercise training of eight weeks possesses certain lowering blood pressure tendency, but no significant influence yet for aortic compliance and cardiovascular tissue structure in spontaneously hypertensive rats.