Geroscience approaches to obesity

Besides aging, obesity is the greatest risk factor for numerous chronic pathologies, including metabolic syndrome, type 2 diabetes, cardiovascular disease, hypertension, and cancer. Preventing and treating obesity would greatly reduce healthcare costs and the impact of the aging process, with estimated savings up to $145,000,000,000. Pharmacological interventions identified by geroscience may prove effective against diet-induced obesity. To test this hypothesis, we fed a 66% kcal/fat diet to nine-month-old C57Bl6/N mice for 6 weeks and treated them with either rapamycin, acarbose, or a combination thereof. Rapamycin, and to a lesser extent acarbose, prevented weight gain and fat accumulation in these mice. We detected increased expression of the Liver Activating Protein (LAP) isoform of the transcription factor CCAT/Enhancer Binding Protein β (C/EBPβ) in the liver of mice treated with rapamycin. C/EBPβ-LAP mediates some of the effects of caloric restriction on nutrient metabolism and increases lifespan in a mouse transgenic model. We tested whether independent activation of C/EBPβ-LAP would recapitulate the effects of rapamycin by treating mice on a high-fat diet with adefovir dipivoxil, a reverse transcriptase inhibitor that can activate LAP in vitro independently of mTOR inhibition. Adefovir dipivoxil reduced weight and fat mass accumulation in mice over the course of 6 weeks. Mice treated with adefovir dipivoxil showed increased expression of genes involved in β-oxidation and lipids mobilization, and reduced activation of fatty acid biosynthesis and lipid storage pathways. Our results identify C/EBPβ-LAP as a potential new target to improve lipid homeostasis in both aging and obesity.

Effect of Entecavir Combined with Adefovir Dipivoxil on Clinical Efficacy and TNF-α and IL-6 Levels in Patients with Hepatitis B Cirrhosis

Objective. The purpose of the study was to investigate the effect of entecavir combined with adefovir dipivoxil on clinical efficacy and TNF-α and IL-6 levels in patients with hepatitis B cirrhosis. Methods. A total of 100 patients with hepatitis B cirrhosis admitted to our hospital between January 2018 and June 2019 were randomly selected and divided into the control group (n = 50) and experimental group (n = 50) according to the order of admission. Among them, the control group patients were treated with entecavir, while the patients in the experimental group received entecavir combined with adefovir dipivoxil. After that, the effective rate of treatment, the incidence of adverse reactions, liver function indexes, liver fibrosis condition, and TNF-α and IL-6 expression levels were all compared between the two groups. Results. The effective rate of treatment in the experimental group was significantly higher than that in the control group, with statistical significance ( p < 0.001 ); the incidence of adverse reactions of the patients in the experimental group was significantly lower than that in the control group, with statistical significance ( p < 0.001 ); the liver function indexes in the experimental group were significantly better than those in the control group, with statistical significance ( p < 0.001 ); the number of patients with liver fibrosis in the experimental group was significantly less than that in the control group, with statistical significance ( p < 0.001 ); the TNF-α and IL-6 expression levels in the experimental group were significantly lower than those in the control group, with statistical significance ( p < 0.001 ). Conclusion. Entecavir combined with adefovir dipivoxil in the treatment of hepatitis B cirrhosis can effectively improve the therapeutic effect and reduce the serum inflammatory factor levels, with high safety, which is worthy of application and popularization.

Role of Plasmatic and Urinary Concentration of Tenofovir Disoproxil Fumarate in a Cohort of Patients Affected by Chronic Hepatitis B

The aim of this study was the evaluation of plasmatic and urinary therapeutic drug monitoring (TDM) of tenofovir disoproxil fumarate (TDF) in a cohort of patients affected by chronic hepatitis B (CHB). In 68 enrolled patients eGFR was 68 ml/min in naive, while in adefovir dipivoxil (ADV) pretreated patients was 55.5 ml/min (p<0.001). The HBV E genotype was related to lower TDF level (β= -0.698, p<0.001). Urinary TDF concentration was related to ADV pretreatment (β=0.829, p<0.001). TDF urinary concentrations maybe useful in clinical management of CHB patients with older age and previous treatment with ADV.