Objective: Fetuin-A may mediate cross-talk between the liver and adipose tissue. We studied the physiologic regulation of fetuin-A and explored its potential regulation by leptin.
Design and methods: Fetuin-A levels were measured in three interventional studies as well as in in vitro experiments. Study 1: 15 lean subjects received placebo or physiologic replacement-dose recombinant human leptin (metreleptin) following short term complete caloric deprivation to induce severe hypoleptinemia; Study 2: 7 women with relative leptin deficiency due to strenuous exercise or low weight received 3 months of metreleptin; Study 3: 17 women with relative leptin deficiency were randomized to receive metreleptin or placebo over 9 months. In study 4 human hepatoma Hep G2 cells were treated with leptin. Fetuin-A mRNA expression and secretion were measured.
Results: Complete caloric deprivation significantly decreased leptin but had no effect on fetuin-A levels. Normalizing leptin levels with metreleptin in hypoleptinemic subjects had no effect on circulating fetuin-A levels. Leptin treatment had no effect on fetuin-A mRNA expression and secretion in vitro.
Conclusions: Circulating fetuin-A levels are not affected by short and long-term energy deprivation. Furthermore, both in vivo and in vitro experiments confirm that fetuin-A is not regulated by leptin.
Trial registration: ClinicalTrials.gov NCT00130117.
Keywords: Alpha-2-Heremans-Schmid glycoprotein; Fetuin-A; Leptin.
Published by Elsevier Inc.