RESUMEN
BACKGROUND: /Objective: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and effective treatments are lacking. Bariatric surgery, including sleeve gastrectomy (SG), is a potential therapeutic strategy for NAFLD, but the molecular mechanisms underlying its effects are not fully understood. In this study, the effects of SG and the underlying mechanisms were evaluated in a mouse model of high-fat diet (HFD)-induced NAFLD. METHODS: C57BL/6 mice were randomly divided into three groups: normal diet with sham operation (NC-Sham group), HFD with sham operation (HFD-Sham group), and HFD with sleeve gastrectomy (HFD-SG group). Glucose metabolism and fat accumulation in the body and liver were analyzed before and after SG. Lipid metabolism and inflammation in the liver were evaluated. Nicotinamide adenine dinucleotide (NAD+) levels as well as nicotinamide riboside kinase (NRK1) and Sirtuin-1 (SIRT1) expression levels were evaluated. RESULTS: SG attenuated the HFD-induced increases in glucose and insulin levels, fat accumulation, and lipid droplet accumulation. Fatty acid biosynthesis, the expression of the metabolism-related genes ACC1, FASN, SCD1, and DGAT1, and the levels of inflammatory factors were higher in HFD mice than in NC mice and decreased after SG. NAD + concentrations were 54.9 ± 13.4 µmol/mg in NC-Sham mice, 37.6 ± 8.1 µmol/mg in HFD-Sham mice, and 79.9 ± 13.0 µmol/mg in HFD-SG mice (p < 0.05). NRK1 and SIRT1 expression increased dramatically after SG at both the RNA and protein levels. CONCLUSION: SG significantly alleviated NAFLD in HFD-induced obese mice with increasing the hepatic NAD + levels and upregulating the NRK1/NAD+/SIRT1 pathway.
Asunto(s)
Cirugía Bariátrica/métodos , Dieta Alta en Grasa/efectos adversos , Gastrectomía/métodos , Expresión Génica/genética , NAD/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/cirugía , Transducción de Señal/genética , Sirtuina 1/metabolismo , Regulación hacia Arriba/genética , Animales , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismoRESUMEN
Fat consumption has been hypothesized to influence pancreatic cancer risk, but the results of epidemiologic studies have been controversial. We conducted a systematic review and meta-analysis of case-control and cohort studies to investigate this issue. Relevant published studies were identified by searching MEDLINE (PubMed) through February 2014. Two authors (Q.-W.S. and Q.-Y.Y.) independently assessed eligibility and the extracted data. Study-specific relative risks (RRs) were pooled using a random-effects model. We also carried out heterogeneity and publication bias analyses. Six cohort and 13 case-control studies with 6159 pancreatic cancer cases and 1,068,476 noncases were included in this meta-analysis. The summary RR for pancreatic cancer for the highest versus lowest intake was 1.04 [95% confidence interval (CI)=0.90-1.20, I²=57.3%, P for heterogeneity=0.001] for total fat. In addition, when separately analyzed by study design, case-control (RR=1.03, 95% CI=0.83-1.27, I²=55.8%, P for heterogeneity=0.007) and cohort studies (RR=1.05, 95% CI=0.85-1.29, I²=66.7%, P for heterogeneity=0.010) yielded similar results. Furthermore, no statistically significant associations were observed in the subgroup analyses on the basis of fat source, geographic location, whether using energy-adjusted models, and whether adjusted for several potential confounders and important risk factors. There was no evidence of publication bias or significant heterogeneity between subgroups on meta-regression analyses. The results of this meta-analysis do not support an independent association between diets high in total fat and pancreatic cancer risk.