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Preadipocyte factor-1 levels are higher in women with hypothalamic amenorrhea and are associated with bone mineral content and bone mineral density through a mechanism independent of leptin.

ABSTRACT: Preadipocyte factor 1 (pref-1) is increased in anorexia nervosa and is associated negatively with bone mineral density (BMD). No previous studies exist on pref-1 in women with exercise-induced hypothalamic amenorrhea (HA), which similar to anorexia nervosa, is an energy-deficiency state associated with hypoleptinemia.Our objective was to evaluate whether pref-1 levels are also elevated and associated with low BMD and to assess whether leptin regulates pref-1 levels in women with HA.Study 1 was a double-blinded, placebo-controlled randomized clinical trial of metreleptin administration in women with HA. Study 2 was an open-label study of metreleptin administration in low physiological, supraphysiological, and pharmacological doses in healthy women volunteers.At Beth Israel Deaconess Medical Center, 20 women with HA and leptin levels higher than 5 ng/ml and nine healthy control women participated in study 1, and five healthy women participated in study 2.For study 1, 20 HA subjects were randomized to receive either 0.08 mg/kg metreleptin (n = 11) or placebo (n = 9). For study 2, five healthy subjects received 0.01, 0.1, and 0.3 mg/kg metreleptin in both fed and fasting conditions for 1 and 3 d, respectively.Circulating pref-1 and leptin levels were measured.Pref-1 was significantly higher in HA subjects vs. controls (P = 0.035) and negatively associated with BMD (? = -0.38; P < 0.01) and bone mineral content (? = -0.32; P < 0.05). Metreleptin administration did not alter pref-1 levels in any study reported herein.Pref-1 is higher in HA subjects than controls. Metreleptin administration at low physiological, supraphysiological, and pharmacological doses does not affect pref-1 levels, suggesting that hypoleptinemia is not responsible for higher pref-1 levels and that leptin does not regulate pref-1.

SUBMITTER: Aronis KN

PROVIDER: S-EPMC3200235 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Preadipocyte factor-1 levels are higher in women with hypothalamic amenorrhea and are associated with bone mineral content and bone mineral density through a mechanism independent of leptin.

Aronis Konstantinos N KN Kilim Holly H Chamberland John P JP Breggia Anne A Rosen Clifford C Mantzoros Christos S CS

The Journal of clinical endocrinology and metabolism 20110727 10

<h4>Context</h4>Preadipocyte factor 1 (pref-1) is increased in anorexia nervosa and is associated negatively with bone mineral density (BMD). No previous studies exist on pref-1 in women with exercise-induced hypothalamic amenorrhea (HA), which similar to anorexia nervosa, is an energy-deficiency state associated with hypoleptinemia.<h4>Objective</h4>Our objective was to evaluate whether pref-1 levels are also elevated and associated with low BMD and to assess whether leptin regulates pref-1 lev ...[more]

PMID: 21795455

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Project description:UnlabelledIn animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition.IntroductionContrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults.MethodsBAT volume (ml) and activity (standard uptake value) were determined by 18F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA.ResultsAmong 24 healthy adults (age 28±1 years, F=10), BAT volumes were 82.4±99.5 ml in women and 49.7±54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4±8.1% (p=0.03), than men. BAT volume correlated positively with total and spine BMD (r2=0.40 and 0.49, respectively, p<0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (p<0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11±2% (p=0.02) and 22±2% (p<0.01), respectively. No associations were observed between BAT parameters and BMD in men.ConclusionsThis study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.

Dataset Information

Preadipocyte factor-1 levels are higher in women with hypothalamic amenorrhea and are associated with bone mineral content and bone mineral density through a mechanism independent of leptin.

Publications

Preadipocyte factor-1 levels are higher in women with hypothalamic amenorrhea and are associated with bone mineral content and bone mineral density through a mechanism independent of leptin.

Similar Datasets

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