Inverse Association of Circulating SIRT1 and Adiposity: A Study on Underweight, Normal Weight, and Obese Patients

Abstract

Context: Sirtuins (SIRTs) are NAD+-dependent deacetylases, cellular sensors to detect energy availability, and modulate metabolic processes. SIRT1, the most studied family member, influences a number of tissues including adipose tissue. Expression and activity of SIRT1 reduce with weight gain and increase in conditions of starvation.Objective: To focus on SIRT1 plasma concentrations in different conditions of adiposity and to correlate SIRT1 with fat content and distribution, energy homeostasis and inflammation in under-weight, normal-weight, and obese individuals.Materials and Methods: 21 patients with anorexia nervosa, 26 normal-weight and 75 patients with obesity were evaluated. Body fat composition by dual-energy X-ray absorptiometry, ultrasound liver adiposity, echocardiographic epicardial fat thickness (EFT), inflammatory (ESR, CRP, and fibrinogen), and metabolic (FPG, insulin, LDL- and HDL-cholesterol, triglycerides) parameters, calculated basal metabolic rate (BMR) and plasma SIRT1 (ELISA) were measured.Results: SIRT1 was significantly higher in anorexic patients compared to normal-weight and obese patients (3.27 ± 2.98, 2.27 ± 1.13, and 1.36 ± 1.31 ng/ml, respectively). Linear regression models for each predictor variable adjusted for age and sex showed that SIRT1 concentration was inversely and significantly correlated with EFT, fat mass %, liver fat content, BMR, weight, BMI, WC, LDL-cholesterol, insulin, ESR. Stepwise multiple regression analysis revealed that age and EFT were the best independent correlates of SIRT1 (β = −0.026 ± 0.011, p = 0.025, and β = −0.516 ± 0.083, p < 0.001, respectively).Conclusions: Plasma SIRT1 shows a continuous pattern that inversely follows the whole spectrum of adiposity. SIRT1 significantly associates with EFT, a strong index of visceral fat phenotype, better than other indexes of adiposity studied here.

Impact of Nutrition on Short-Term Exercise-Induced Sirtuin Regulation: Vegans Differ from Omnivores and Lacto-Ovo Vegetarians

“…To our knowledge, there is no evidence that sirtuin activity in blood represents sirtuins leaking out of solid organs (skeletal and cardiac muscle). It has previously been shown that sirtuin levels in blood correlate with different organ dysfunctions like coronary heart disease in obese patients [8][9][10]62] or type 1 and type 2 diabetes [11]. Exercise leads to metabolic stress in different organs and it would not ethically be sound to take biopsies from multiple organs in humans.…”

“…The acetylation level of the mitochondrial proteome is 65% [7] which makes these proteins amenable to regulation by sirtuins. Blood levels of sirtuins were shown to correlate with several organ dysfunctions like coronary heart disease in obese patients [8][9][10] or type 1 and type 2 diabetes [11].…”

SIRT1 accelerates the progression of activity-based anorexia

“…In addition to being linked to physical activity, SIRT1 is implicated in the development of addictions 11,12 , anxiety 13,14 , and depression [14][15][16][17] , all of which are elements of AN, reinforcing the notion that this enzyme might play a key role in the pathology of AN. Furthermore, two recent studies showed an upregulation of SIRT1 expression in AN models of rodents 18,19 , while another found an increase in SIRT1 protein levels in humans with AN 20 , all of which further suggest a link between AN and SIRT1.…”

Blood SIRT1 Shows a Coherent Association with Leptin and Adiponectin in Relation to the Degree and Distribution of Adiposity: A Study in Obesity, Normal Weight and Anorexia Nervosa

“…The SIRT1 levels were determined according to the manufacturer's instructions using quantitative ELISAs (MyBioSource, Cod. GDMBS705558) as previously described [13]. Adiponectin was measured by Human Total Adiponectin/Acrp30 Quantikine ELISA kit (DRP300, R&D Systems, Minneapolis, MN, USA).…”

“…SIRT1 modulates gluconeogenesis in the liver, pancreatic ß cell insulin secretion [10], adipocyte differentiation [11] and heart protection [12]. In the case of overnutrition, tissue and plasma levels of SIRT1 are reduced, predisposing to metabolic derangement and its sequelae [13,14]. Indeed, SIRT1 inversely correlates with FM, and its reduction is associated with liver steatosis and increased epicardial fat thickness (EFT) in obese patients [15][16][17].…”