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Interruption of bile acid recirculation through inhibition of the apical sodium-dependent bile acid transporter (ASBT) is a promising strategy to alleviate hepatic cholesterol accumulation in non-alcoholic steatohepatitis (NASH), and improve the metabolic aspects of the disease. Potential disease-attenuating effects of the ASBT inhibitor volixibat (5, 15, and 30 mg/kg) were investigated in high-fat diet (HFD)-fed Ldlr-/-.Leiden mice over 24 weeks. Plasma and fecal bile acid levels, plasma insulin, lipids, and liver enzymes were monitored. Final analyses included liver histology, intrahepatic lipids, mesenteric white adipose tissue mass, and liver gene profiling. Consistent with its mechanism of action, volixibat significantly increased the total amount of bile acid in feces. At the highest dose, volixibat significantly attenuated the HFD-induced increase in hepatocyte hypertrophy, hepatic triglyceride and cholesteryl ester levels, and mesenteric white adipose tissue deposition. Non-alcoholic fatty liver disease activity score (NAS) was significantly lower in volixibat-treated mice than in the HFD controls. Gene profiling showed that volixibat reversed the inhibitory effect of the HFD on metabolic master regulators, including peroxisome proliferator-activated receptor-γ coactivator-1β, insulin receptor, and sterol regulatory element-binding transcription factor 2. Volixibat may have beneficial effects on physiological and metabolic aspects of NASH pathophysiology.

BACKGROUND:We conducted a systematic review to assess the effectiveness of smoking cessation, physical activity (PA), diet, and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases (NCDs). METHODS:We searched for randomised controlled trials (RCTs) of mobile-based NCD prevention interventions using MEDLINE, EMBASE, Global Health, CINAHL (Jan 1990-Jan 2016). Two authors extracted data. FINDINGS:71 trials were included: smoking cessation (n = 18); PA (n = 15), diet (n = 3), PA and diet (n = 25); PA, diet, and smoking cessation (n = 2); and harmful alcohol consumption (n = 8). 4 trials had low risk of bias. The effect of SMS-based smoking cessation support on biochemically verified continuous abstinence was pooled relative risk [RR] 2.19 [95% CI 1.80-2.68], I2 = 0%) and on verified 7 day point prevalence of smoking cessation was pooled RR 1.51 [95% CI 1.06-2.15], I2 = 0%, with no reported adverse events. There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention. The effect of SMS-based diet and PA interventions on: incidence of diabetes was pooled RR 0.67 [95% CI 0.49, 0.90], I2 = 0.0%; end-point weight was pooled MD -0.99Kg [95% CI -3.63, 1.64] I2 = 29.4%; % change in weight was pooled MD -3.1 [95%CI -4.86- -1.3] I2 0.3%; and on triglyceride levels was pooled MD -0.19 mmol/L [95% CI -0.29, -0.08], I2 = 0.0%. The results of other pooled analyses of the effect of SMS-based diet and PA interventions were heterogenous (I2 59-90%). The effects of alcohol reduction interventions were inconclusive. CONCLUSIONS:Smoking cessation support delivered by SMS increases quitting rates. Trials of PA interventions reporting outcomes ≥3 months showed no benefits. There were at best modest benefits of diet and PA interventions. The effects of the most promising SMS-based smoking, diet and PA interventions on morbidity and mortality in high-risk groups should be established in adequately powered RCTs.