We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
SIRT-1 Expression Is Increased in Human Obesity and Decreases Following Caloric Restriction and Weight Loss.
- Authors
Ghanim, Husam; Sia, Ching Ling; Mohanty, Priya; Dandona, Paresh
- Abstract
It has been shown that caloric restriction (CR) increases life expectancy in yeast, C. elegans and drosophila. This increase is mediated by the histone deacetylase (HDAC) silence information regulator-2 (Sir-2). Sirtuin -1 (SIRT-1), the mammalian orthlog of Sir-2, and SIRT-6 (another sirtuin) have been proposed as modulates of life span in mammals. However, data on and its regulation with CR are hitherto not available. Since oxidative and inflammatory stress are known to be associated with aging and since obesity is characterized by oxidative and inflammatory stress, we hypothesized that obesity in the human is associated with decreased SIRT-1 and/or SIRT-6 expression and that CR would result in an increase in SIRT-land/or SIRT-6 expression in association with reduction in insulin resistance and inflammation. Fasting blood samples were collected from two groups, 16 each, of normal weight controls (Body Mass Index (BMI) of 22.6±1.9 Kg/m²) and healthy obese (BMI=40.0±4.4 Kg/m²) female subjects. Fasting blood samples were also collected from another 10 healthy obese subjects (BMI 37.5±3.4 kg/m²) at baseline and at 4 weeks following normal diet followed by another blood draw after 4 weeks of 1000 Calorie/day diet. Total RNA was isolated from mononuclear circulating cells (MNC) and RT-PCR was performed. Contrary to our hypothesis, SIRT1 mRNA expression was significantly higher (by about 2.5 fold, P<0.001) in MNC from obese female subjects compared to MNC isolated from lean subjects while there was no significant difference in the expression of SIRT-6 between the two groups. CR (1000 calorie per day for 4 weeks) in obese subjects was associated with a significant weight loss (3.9%, P<0.05) and insulin sensitizing effect as measured by HOMA-IR. SIRT1 mRNA expression from the MNC fell significantly by 25% from baseline (P<0.001) while there was no change in controls. There was no significant change in SIRT-6 expression following caloric restriction. We conclude that (1.) obesity is associated with an increase in SIRT-1 expression; (2.) caloric restriction leads to a fall in SIRT-1; and (3.) SIRT-6 is not altered in obesity and does not change following dietary restriction and weight loss. SIRT-1 in the human is regulated by macronutrient intake and obesity. Its role in the regulation of aging processes requires further elucidation.
- Subjects
HISTONE deacetylase; AMIDASES; OBESITY; LOW-calorie diet; WEIGHT loss
- Publication
Diabetes, 2007, Vol 56, pA72
- ISSN
0012-1797
- Publication type
Article