title: Serum osteocalcin is associated with improved metabolic state via adiponectin in females versus testosterone in males. Gender specific nature of the bone-energy homeostasis axis.
abstract: OBJECTIVE
  The osteoblast-derived protein osteocalcin (OCN) is known to be involved in glucose metabolism by increasing adiponectin secretion from adipocytes. Recently, OCN was also found to enhance testosterone production in mouse testes, suggesting that OCN effects on energy metabolism may be mediated through testosterone. Our aim was to assess a possible gender difference in the metabolic effect of OCN in humans.
  
  
  METHODS
  We included 135 women and 155 men exhibiting changes in glucose tolerance in our study. Oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) and a hyperinsulinemic normoglycemic clamp were performed. For clamp indices, whole body (M1) and muscle (M2) glucose uptake values were used. Leptin, adiponectin serum lipid, lipoprotein, total serum OCN and testosterone levels, and body composition were determined.
  
  
  RESULTS
  Higher OCN values were associated with improving metabolic state in both genders. Adiponectin and OCN correlated significantly only in females (r=+0.254, p=0.0029), while in men, testosterone and OCN values showed a significant positive correlation (r=+0.243, p=0.0023), independent of age, BMI, HbA1c and body composition. In women, adiponectin was confirmed by feature selection analysis as being an independent determinant of OCN, in addition to age and three of the IVGTT glucose values. In men, besides M1, BMI, M2, leptin, body fat percent, and the 90-minute OGTT glucose reading testosterone, but not adiponectin were identified as independent contributors for OCN.
  
  
  CONCLUSIONS
  We confirmed the 'classic' adiponectin-mediated insulin-sensitising effect of OCN only in females. In men, a testosterone-mediated OCN metabolic effect is more likely.
authors.affiliation: Department of Metabolism, Drug Research Centre, Balatonfüred, Hungary. Electronic address: barbara.buday@drc.hu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Buday
authors.forename: Ferenc Péter
authors.initials: FP
authors.lastname: Pach
authors.forename: Botond
authors.initials: B
authors.lastname: Literati-Nagy
authors.forename: Marta
authors.initials: M
authors.lastname: Vitai
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Vecsei
authors.forename: Laszlo
authors.initials: L
authors.lastname: Koranyi
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000378:metabolism; D000328:Adult; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood* / Q000378:metabolism; D013739:Testosterone / Q000097:blood* / Q000378:metabolism
chemical_list: D052242:Adiponectin; D015675:Osteocalcin; D013739:Testosterone
keywords: 2DM; AIR; AUC; Adiponectin; BFP; BMI; DEXA; FFA; GI; HOMA-IR; IFG; IGI; IGT; IVGTT; Insulin resistance; M1; M2; NGT; OCN; OGTT; Osteocalcin; Testosterone; WC; acute insulin response of IVGTT; area under the curve; body fat percent; body mass index; clamp measured muscle glucose uptake; clamp measured whole body glucose uptake; dual energy X-ray absorptiometry; free fatty acid; glucose intolerant; homeostasis model assessment of insulin resistance; impaired fasting glucose; impaired glucose tolerant; insulogenic index of IVGTT; intravenous glucose tolerance test; normal glucose tolerant; oral glucose tolerance test; osteocalcin; type 2 diabetes mellitus; ucOCN; undercarboxylated osteocalcin; waist circumference