Adipose tissue and liver expression of SIRT1, 3, and 6 increase after extensive weight loss in morbid obesity.
OBJECTIVE
Severe obesity is associated with a state of chronic inflammation. Sirtuins (SIRT) are a family of conserved enzymes which are able to affect many metabolic and inflammatory pathways thereby potentially improving health and increasing lifespan.


METHODS
We investigated the effect of weight loss on subcutaneous adipose tissue and liver mRNA and immunohistochemical expression of SIRT1, SIRT3, and SIRT6. Twenty-nine severely obese patients undergoing laparoscopic adjustable gastric banding (LAGB) were studied. Tissue samples were collected before and 6months after LAGB surgery. Tissue mRNA expression levels of SIRT1, SIRT3, and SIRT6 were correlated with clinical, biochemical, and histological parameters. In vitro, we studied sirtuin expression in native and stimulated monocytes, adipocytes, and hepatocytes.


RESULTS
SIRT1, SIRT3, and SIRT6 mRNA expression was higher in the subcutaneous adipose tissue than in the liver. Weight loss resulted in a significant induction of SIRT1, SIRT3, and SIRT6 expression in the subcutaneous adipose tissue. In the liver, a significant increase after weight loss was observed, particularly for SIRT3 and SIRT6 mRNA expression; immunohistochemically, SIRT1 and SIRT3 expression was upregulated. Endotoxin and tumor necrosis factor-alpha suppressed SIRT1, SIRT3, and SIRT6 expression in human monocytes. The same stimuli suppressed total sirtuin deacetylase activity again, mainly in monocytes and less in adipocytes and hepatocytes.


CONCLUSIONS
The relative abundance of adipose tissue mRNA expression of certain sirtuins exceeds its expression in the liver. Extensive weight loss increases sirtuin expression significantly both in adipose tissue and liver, probably as a consequence of reduced inflammation.
Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Innsbruck, Austria; Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck, Austria.
Alexander R
AR
Moschen
Verena
V
Wieser
Romana R
RR
Gerner
Alexandra
A
Bichler
Barbara
B
Enrich
Patrizia
P
Moser
Christoph F
CF
Ebenbichler
Susanne
S
Kaser
Herbert
H
Tilg
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism*; D056564:Sirtuin 1 / Q000032:analysis / Q000235:genetics*; D056566:Sirtuin 3 / Q000032:analysis / Q000235:genetics*; D037761:Sirtuins / Q000032:analysis / Q000235:genetics*; D050151:Subcutaneous Fat / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015431:Weight Loss
D014409:Tumor Necrosis Factor-alpha; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; C516592:SIRT6 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3; D037761:Sirtuins
Insulin resistance; Metabolism; NAFLD; SIRT1; SIRT3; SIRT6