Current evidence indicates that inverse association between leptin level and 25(OH)D concentration was observed in observational studies , which was not demonstrated in intervention studies with high heterogeneity .
We aim ed to investigate the potential association between vitamin D and serum leptin levels by pooling together the results from observational studies and clinical trials .
Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans
Aim /hypothesisLeptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors , but its role in regulating angiogenesis has never been studied in humans . Methods The potential angiogenic effect of two doses of metreleptin ( 50 and 100 ng/ml ) was evaluated in vitro , using a novel three-dimensional angiogenesis assay . Fifteen healthy , normoleptinaemic volunteers were administered both a physiological ( 0.1 mg/kg ) and a pharmacological ( 0.3 mg/kg ) single dose of metreleptin , in vivo , on two different inpatient admissions separated by 1–12 weeks . Serum was collected at 0 , 6 , 12 and 24 h after metreleptin administration . Twenty lean women , with leptin levels < 5 ng/ml , were r and omised in a 1:1 fashion to receive either physiological replacement doses of metreleptin ( 0.04–0.12 mg/kg q.d . ) or placebo for 32 weeks . Serum was collected at 0 , 8 , 20 and 32 weeks after r and omisation . Proteomic angiogenesis array analysis was performed to screen for angiogenic factors . Circulating concentrations of angiogenin , angiopoietin-1 , platelet derived endothelial factor (PDGF)-AA , matrix metalloproteinase ( MMP ) 8 and 9 , endothelial growth factor ( EGF ) and vascular EGF ( VEGF ) were also measured . Results Both metreleptin doses failed to induce angiogenesis in the in vitro model . Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration , circulating concentrations of angiogenesis markers did not change significantly in vivo . Conclusions /interpretationsThis is the first study that examines the effect of metreleptin administration in angiogenesis in humans . Metreleptin administration does not regulate circulating angiogenesis related factors in humans . Clinical trial registration : Clinical Trials.gov NCT00140205 and NCT00130117 . Funding : This study was supported by National Institutes of Health-National Center for Research Re sources grant M01-RR-01032 ( Harvard Clinical and Translational Science Center ) and grant number UL1 RR025758 . Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785 , 79929 and 81913 , and AG032030
Current evidence indicates that inverse association between leptin level and 25(OH)D concentration was observed in observational studies , which was not demonstrated in intervention studies with high heterogeneity .
We aim ed to investigate the potential association between vitamin D and serum leptin levels by pooling together the results from observational studies and clinical trials .