Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +/ Sirtuin-1 pathway in mice.
Animals
Bariatric Surgery
/ methods
Diet, High-Fat
/ adverse effects
Disease Models, Animal
Gastrectomy
/ methods
Gene Expression
/ genetics
Male
Mice, Inbred C57BL
NAD
/ metabolism
Non-alcoholic Fatty Liver Disease
/ etiology
Signal Transduction
/ genetics
Sirtuin 1
/ metabolism
Up-Regulation
/ genetics
NAD+
NAFLD
NRK1
SIRT1
Sleeve gastrectomy
Journal
Asian journal of surgery
ISSN: 0219-3108
Titre abrégé: Asian J Surg
Pays: Netherlands
ID NLM: 8900600
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
14
04
2020
revised:
07
05
2020
accepted:
14
05
2020
pubmed:
28
7
2020
medline:
1
6
2021
entrez:
27
7
2020
Statut:
ppublish
Résumé
/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. 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. 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. SG significantly alleviated NAFLD in HFD-induced obese mice with increasing the hepatic NAD + levels and upregulating the NRK1/NAD+/SIRT1 pathway.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
SG significantly alleviated NAFLD in HFD-induced obese mice with increasing the hepatic NAD + levels and upregulating the NRK1/NAD+/SIRT1 pathway.
Identifiants
pubmed: 32712045
pii: S1015-9584(20)30166-4
doi: 10.1016/j.asjsur.2020.05.030
pii:
doi:
Substances chimiques
NAD
0U46U6E8UK
Sirt1 protein, mouse
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
213-220Informations de copyright
Copyright © 2020. Published by Elsevier Taiwan LLC.
Déclaration de conflit d'intérêts
Declaration of competing interest None.