Circulating fetuin-A levels are not affected by short and long-term energy deprivation and/or by leptin administration

Abstract

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.

Conflict of interest statement

Conflict of interest

Dr. CS Mantzoros has received research support for investigator initiated trials from Amylin Pharmaceuticals, Inc. through Beth Israel Deaconess Medical Center. All other authors have no relevant conflicts of interest related to this research.

Published by Elsevier Inc.

Figures

Fig. 1

A: Measurement of Fetuin-A at the beginning (day 1) and end (day 3 or 4) of a baseline fed condition, 72-h complete fasting with administration of placebo, and 72-h complete fasting with administration of metreleptin (n = 8 normal-weight men and 7 normal-weight women). ■ day 1; □ final day, p = 0.13. B: Measurement of Fetuin-A in 17 women with chronic leptin deficiency and HA randomized to receive metreleptin or placebo for 36 weeks. —Placebo—Metreleptin, repeated measures ANOVA, p = 0.19.