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Pouneh K Fazeli, Alex Faje, Miriam A Bredella, Sai Polineni, Stephen Russell, Megi Resulaj, Clifford J. Rosen and Anne Klibanski

Objective: In anorexia nervosa, a psychiatric disease characterized by self-induced starvation and a model of chronic undernutrition, levels of subcutaneous (SAT) and visceral (VAT) adipose tissue are low, whereas marrow adipose tissue (MAT) levels are elevated compared to normal-weight women. The reason for this paradoxical elevation of an adipose tissue depot in starvation is not known. We sought to understand changes in MAT in response to sub-acute changes in weight and to compare these changes with those of other fat depots and body composition parameters.

Design and Methods: We conducted a 12-month longitudinal study including 46 premenopausal women (n=26 with anorexia nervosa and n=20 normal-weight controls) with a mean (SEM) age of 28.2+/-0.8 years. We measured MAT, SAT, VAT, and bone mineral density (BMD) at baseline and after 12 months.

Results: At baseline, SAT (p<0.0001), VAT (p<0.02) and BMD of the spine and hip (p<0.0002) were significantly lower and vertebral and metaphyseal MAT (p<0.001) significantly higher in anorexia nervosa compared to controls. Weight gain over 12 months was associated with increases not only in SAT and VAT, but also epiphyseal MAT (p<0.03). Changes in epiphyseal MAT were positively associated with changes in BMD (p<0.02).

Conclusions: In contrast to the steady-state, in which MAT levels are higher in anorexia nervosa and MAT and BMD are inversely associated, short-term weight gain is associated with increases in both MAT and BMD. These longitudinal data demonstrate the dynamic nature of this fat depot and provide further evidence of its possible role in mineral metabolism.

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Miriam A Bredella, Eleanor Lin, Danielle J Brick, Anu V Gerweck, Lindsey M Harrington, Martin Torriani, Bijoy J Thomas, David A Schoenfeld, Anne Breggia, Clifford J Rosen, Linda C Hemphill, Zida Wu, Nader Rifai, Andrea L Utz and Karen K Miller

Objective

Abdominal adiposity is associated with increased cardiovascular risk and decreased GH secretion. The objective of our study was to determine the effects of GH on body composition and cardiovascular risk markers in abdominally obese women.

Materials and methods

In this randomized, double-blind, placebo-controlled study, 79 obese premenopausal women received GH vs placebo for 6 months. Primary endpoints were i) total abdominal (total abdominal adipose tissue, TAT) fat by computed tomography (CT) (body composition) and ii) high-sensitivity C-reactive protein (hsCRP) (cardiovascular risk marker). Body composition was assessed by CT, dual-energy X-ray absorptiometry, and proton MR spectroscopy. Serum cardiovascular risk markers, carotid intima-media thickness, and endothelial function were measured.

Results

Mean 6-month GH dose was 1.7±0.1 mg/day, resulting in a mean IGF1 SDS increase from −1.7±0.08 to −0.1±0.3 in the GH group. GH administration decreased TAT and hsCRP compared with placebo. In addition, it increased thigh muscle mass and lean body mass and decreased subcutaneous abdominal and trunk fat, tissue plasminogen activator, apoB, and apoB/low-density lipoprotein compared with placebo. Visceral adipose tissue (VAT) decreased and intramyocellular lipid increased within the GH group. Six-month change in IGF1 levels was negatively associated with 6-month decrease in TAT and VAT. One subject had a 2 h glucose >200 mg/ml at 3 months; four subjects, three of whom were randomized to GH, had 2 h glucose levels >200 mg/ml at the end of the study.

Conclusion

GH administration in abdominally obese premenopausal women exerts beneficial effects on body composition and cardiovascular risk markers but is associated with a decrease in glucose tolerance in a minority of women.