title: Preliminary data on the relationship between circulating levels of Sirtuin 4, anthropometric and metabolic parameters in obese subjects according to growth hormone/insulin-like growth factor-1 status.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Italy. Electronic address: sisavast@unina.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Savastano
authors.affiliation: IRCCS SDN, Napoli, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Di Somma
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.affiliation: Coleman & IOS srl, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Barrea
authors.affiliation: Dipartimento di Scienze Motorie e del Benessere Università Parthenope Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Orio
authors.affiliation: Center of Obesity and Eating Disorders, Stella Maris Mediterraneum Foundation, C/da S. Lucia, Chiaromonte, 80035 Potenza, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Finelli
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pasanisi
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Contaldo
authors.affiliation: Centro Ricerche Oncologiche di Mercogliano, Istituto Nazionale Per Lo Studio e La Cura Dei Tumori "Fondazione Giovanni Pascale", IRCCS, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tarantino
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000097:blood*; D009765:Obesity / Q000097:blood* / Q000378:metabolism; D010084:Oxidation-Reduction; D012307:Risk Factors; D037761:Sirtuins / Q000097:blood*; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C583557:IGF1 protein, human; D024101:Mitochondrial Proteins; D014280:Triglycerides; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C525357:SIRT4 protein, human; D037761:Sirtuins
keywords: Body composition; Cardio-metabolic risk; GH/IGF-1 axis; Serum Sirtuin 4