SIRT1 transcription is decreased in visceral adipose tissue of morbidly obese patients with severe hepatic steatosis.
BACKGROUND
Visceral adipose tissue is known to release greater amounts of adipokines and free fatty acids into the portal vein, being one of the most predictive factors of nonalcoholic fatty liver disease (NAFLD). Our study has the purpose to evaluate sirtuin 1 (SIRT1), adiponectin, Forkhead/winged helix (FOXO1), peroxisome proliferator-activated receptor (PPAR)gamma1-3, and PPARbeta/delta mRNA expression in morbidly obese patients in three different lipid depots: visceral (VAT), subcutaneous (SAT), and retroperitoneal (RAT). Recent studies suggest that SIRT1, a NAD(+)-dependent deacetylase, protects rats from NAFLD.


METHODS
We divided the patients in two groups: those with slight or moderate steatosis (hepatic steatosis, HS) and other comprising individuals with severe steatosis associated or not with necroinflammation and fibrosis (severe hepatic steatosis, SHS). The adipose tissue depots were obtained during bariatric surgery. Total RNAs were extracted using TRIzol. The amount of genes of interest was determined by quantitative real-time polymerase chain reaction.


RESULTS
When comparing the two groups of patients, a decrease in SIRT1 was observed in VAT of morbidly obese patients in SHS group (p = 0.006). The mRNA expression of the other genes showed no differences in VAT. No difference was found either in SAT or in RAT for all genes in the study. In addition, the homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in SHS group compared to HS (p = 0.006). Also, our results show that the mRNA expression of SIRT1 and the value of HOMA-IR were positively correlated in VAT of SHS patients (r = 0.654; p = 0.048).


CONCLUSIONS
Downregulation of SIRT1 mRNA expression in VAT of SHS could be possible impairing mitochondria biogenesis and fatty acid oxidation, promoting severe steatosis in obese patients. Our results provide a possible proof of SIRT1 protective potential in VAT against NAFLD in humans.
Costa
Cíntia dos Santos
Cdos S
Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos 2600-anexo, 90035-003 Porto Alegre, Rio Grande do Sul, Brazil.
Hammes
Thais Ortiz
TO
Rohden
Francieli
F
Margis
Rogério
R
Bortolotto
Josiane Woutheres
JW
Padoin
Alexandre Vontobel
AV
Mottin
Cláudio Cora
CC
Guaragna
Regina Maria
RM
D005234:Fatty Liver / Q000150:complications*; D015390:Gastric Bypass / Q000379:methods; D015870:Gene Expression; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D009767:Obesity, Morbid / Q000150:complications / Q000235:genetics* / Q000601:surgery; D056564:Sirtuin 1 / Q000235:genetics*; D050151:Subcutaneous Fat / Q000378:metabolism*; D014158:Transcription, Genetic; D016896:Treatment Outcome
C447939:SIRT1 protein, human; D056564:Sirtuin 1