Silvia Savastano1, Carolina Di Somma2, Annamaria Colao3, Luigi Barrea4, Francesco Orio5, Carmine Finelli6, Fabrizio Pasanisi3, Franco Contaldo3, Giovanni Tarantino7. 1. Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Italy. Electronic address: sisavast@unina.it. 2. IRCCS SDN, Napoli, Italy. 3. Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Italy. 4. Coleman & IOS srl, Naples, Italy. 5. Dipartimento di Scienze Motorie e del Benessere Università Parthenope Napoli, Italy. 6. Center of Obesity and Eating Disorders, Stella Maris Mediterraneum Foundation, C/da S. Lucia, Chiaromonte, 80035 Potenza, Italy. 7. Centro Ricerche Oncologiche di Mercogliano, Istituto Nazionale Per Lo Studio e La Cura Dei Tumori "Fondazione Giovanni Pascale", IRCCS, Italy.
Abstract
BACKGROUND: The main components of GH/insulin-like growth factor (IGF)-1 axis and Sirtuin 4 (Sirt4), highly expressed in liver and skeletal muscle mitochondria, serve as active regulators of mitochondrial oxidative capacity with opposite functions. In obesity both GH/IGF-1 status and serum Sirt4 levels, likely mirroring its reduced mitochondrial expression, might be altered. OBJECTIVE: To evaluate the association between circulating levels of Sirt4, body composition, metabolic parameters and cardio-metabolic risk profile in obese patients according to their different GH/IGF-1 status. DESIGN: Cross-sectional study with measurement of serum Sirt4, GH after GH releasing hormone (GHRH)+Arginine test, IGF-1 and assessment of body composition, glucose and lipid metabolism in 50 class II-III obese subjects (BMI 35.6 to 62.1 kg/m(2)) and 15 normal weight subjects. Low GH secretion and IGF-1 were defined using pre-determined cutoff-points. The Homeostatic Metabolic Assessment of insulin resistance index and Visceral adiposity index were also calculated. The association of Sirt4 with peak stimulated GH and IGF-1, body composition, metabolic parameters and cardio-metabolic risk profile was assessed. RESULTS: Serum Sirt4 was inversely related to anthropometric and metabolic parameters and positively related to peak GH and IGF-1. After adjusting for peak GH and IGF-1, the relationships between Sirt4 and BMI became not significant. At multiple regression analysis IGF-1 (p<0.001) was the independent predictor for Sirt4. CONCLUSION: There was a close relationship between low IGF-1 and low serum Sirt4. This observation suggested that in obese patients, low GH/IGF-1 status was likely associated with a major compensatory decrease in circulating levels of Sirt4 to oppose to its negative regulator effect on mitochondrial oxidative capacity.
BACKGROUND: The main components of GH/insulin-like growth factor (IGF)-1 axis and Sirtuin 4 (Sirt4), highly expressed in liver and skeletal muscle mitochondria, serve as active regulators of mitochondrial oxidative capacity with opposite functions. In obesity both GH/IGF-1 status and serum Sirt4 levels, likely mirroring its reduced mitochondrial expression, might be altered. OBJECTIVE: To evaluate the association between circulating levels of Sirt4, body composition, metabolic parameters and cardio-metabolic risk profile in obesepatients according to their different GH/IGF-1 status. DESIGN: Cross-sectional study with measurement of serum Sirt4, GH after GH releasing hormone (GHRH)+Arginine test, IGF-1 and assessment of body composition, glucose and lipid metabolism in 50 class II-III obese subjects (BMI 35.6 to 62.1 kg/m(2)) and 15 normal weight subjects. Low GH secretion and IGF-1 were defined using pre-determined cutoff-points. The Homeostatic Metabolic Assessment of insulin resistance index and Visceral adiposity index were also calculated. The association of Sirt4 with peak stimulated GH and IGF-1, body composition, metabolic parameters and cardio-metabolic risk profile was assessed. RESULTS: Serum Sirt4 was inversely related to anthropometric and metabolic parameters and positively related to peak GH and IGF-1. After adjusting for peak GH and IGF-1, the relationships between Sirt4 and BMI became not significant. At multiple regression analysis IGF-1 (p<0.001) was the independent predictor for Sirt4. CONCLUSION: There was a close relationship between low IGF-1 and low serum Sirt4. This observation suggested that in obesepatients, low GH/IGF-1 status was likely associated with a major compensatory decrease in circulating levels of Sirt4 to oppose to its negative regulator effect on mitochondrial oxidative capacity.
Authors: Luigi Barrea; Giovanni Tarantino; Carolina Di Somma; Giovanna Muscogiuri; Paolo Emidio Macchia; Andrea Falco; Annamaria Colao; Silvia Savastano Journal: Oxid Med Cell Longev Date: 2017-06-15 Impact factor: 6.543