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

Abstract

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, and with leptin and adiponectin, it regulates metabolic homeostasis. Widely studied in tissues, SIRT1 is under evaluation as a plasmatic marker. We aimed at assessing whether circulating SIRT1 behaves consistently with leptin and adiponectin in conditions of deficiency, excess or normal fat content. Eighty subjects were evaluated: 27 with anorexia nervosa (AN), 26 normal-weight and 27 with obesity. Bloodstream SIRT1, leptin and adiponectin (ELISA), total and trunk fat mass (FM) %, abdominal visceral adipose tissue, liver steatosis and epicardial fat thickness (EFT) were assessed. For each fat store, the coefficient of determination (R2) was used to evaluate the prediction capability of SIRT1, leptin and adiponectin. Plasma SIRT1 and adiponectin coherently decreased with the increase of FM, while the opposite occurred with leptin. Mean levels of each analyte were different between groups (p < 0.005). A significant association between plasma variables and FM depots was observed. SIRT1 showed a good predictive strength for FM, particularly in the obesity group, where the best R2 was recorded for EFT (R2 = 0.7). Blood SIRT1, adiponectin and leptin behave coherently with FM and there is synchrony between them. The association of SIRT1 with FM is substantially superimposable to that of adiponectin and leptin. Given its homeostatic roles, SIRT1 may deserve to be considered as a plasma clinical/biochemical parameter of adiposity and metabolic health.

Circulating SIRT1 and Sclerostin Correlates with Bone Status in Young Women with Different Degrees of Adiposity

“…As already described, we found the highest levels of SIRT1 in the underweight group of patients [ 10 , 21 ]. Accordingly, mice under calorie restriction with a significant loss of body weight show the upregulation of SIRT1 mRNA expression in bone associated with increased bone mass [ 16 ].…”

“…Some studies on sclerostin and bone reported this condition [ 23 , 57 , 58 , 59 ] and, in some cases, higher serum sclerostin was measured in women with normal BMD compared to women with osteoporosis [ 23 ]. However, the subtle relationship between excess fat, weight load and skeletal mass could be made more complex by the impaired adipokine production being secondary to increased fat mass [ 21 ]. Indeed, an increased risk of fragility fractures, despite a normal BMD, has been associated with secondary factors [ 60 ].…”

“…Whole-body fat mass (FM, %), abdominal visceral adipose tissue (VAT, cm 3 ) and lean mass (kg) were also measured using the DXA technique. Body composition analysis of soft tissue was performed using the QDR2000 Product Software, version 13.5.3 A (Hologic, Middlesex County, MA, USA) and the regional limits were set as previously described [ 21 ].…”

“…In this scenario, the SIRT1/sclerostin pathway could represent an interesting way to evaluate the bone status in patients with different degrees of adiposity. Indeed, circulating SIRT1 shows a negative correlation with fat mass and a coherent trend with the well-recognized adipokines leptin and adiponectin [ 9 , 21 ], indicating a valid surrogate marker of adiposity; in contrast, sclerostin increases with fat [ 22 , 23 , 24 ]. Their mutual interaction still deserves to be clarified in relation to body composition and bone density and quality.…”

The regulatory role of the SIRT1/FoxO1 pathway in the prevention of insulin resistance in skeletal muscle by aerobic exercise in mice

“…By evaluating the serum SIRT1 levels of 80 subjects, it was found that its content was closely and positively correlated with leptin and adiponectin. SIRT1 can be used as a plasma marker in clinical applications to evaluate energy metabolism and can be applied to weight management in obese people [14,15].…”