Marrow fat and preadipocyte factor‐1 levels decrease with recovery in women with anorexia nervosa

Women with anorexia nervosa (AN) have elevated marrow fat mass despite low visceral and subcutaneous fat depots, which is inversely associated with bone mineral density (BMD). Whether marrow fat mass remains persistently elevated or decreases with recovery from AN is currently unknown. In this study, we investigated changes in marrow fat in women who have recovered from AN (AN‐R). We also studied the relationship between preadipocyte factor (Pref)‐1—a member of the EGF‐like family of proteins and regulator of adipocyte and osteoblast differentiation—and fat depots and BMD in AN‐R compared with women with AN and healthy controls (HC). We studied 29 women: 14 with active or recovered AN (30.7 + 2.2 years [mean ± SEM]) and 15 normal‐weight controls (27.8 ± 1.2 years). We measured marrow adipose tissue (MAT) of the L4 vertebra and femur by 1H‐magnetic resonance spectroscopy; BMD of the spine, hip, and total body by DXA; and serum Pref‐1 and leptin levels. We found that MAT of the L4 vertebra was significantly lower in AN‐R compared with AN (p = 0.03) and was comparable to levels in HC. Pref‐1 levels were also significantly lower in AN‐R compared with AN (p = 0.02) and comparable to levels in healthy controls. Although Pref‐1 was positively associated with MAT of the L4 vertebra in AN (R = 0.94; p = 0.002), we found that it was inversely associated with MAT of the L4 vertebra in HC (R = −0.71; p = 0.004). Therefore, we have shown that MAT and Pref‐1 levels decrease with recovery from AN. Our data suggest that Pref‐1 may have differential effects in states of nutritional deprivation compared with nutritional sufficiency. © 2012 American Society for Bone and Mineral Research.

[1]  L. Lynch,et al.  Preadipocyte factor-1 is associated with metabolic profile in severe obesity. , 2011, The Journal of clinical endocrinology and metabolism.

[2]  M. Bredella,et al.  Vertebral Bone Marrow Fat Is Positively Associated With Visceral Fat and Inversely Associated With IGF‐1 in Obese Women , 2011, Obesity.

[3]  A. Breggia,et al.  Preadipocyte factor-1 is associated with marrow adiposity and bone mineral density in women with anorexia nervosa. , 2010, The Journal of clinical endocrinology and metabolism.

[4]  M. Bredella,et al.  Increased bone marrow fat in anorexia nervosa. , 2009, The Journal of clinical endocrinology and metabolism.

[5]  G. Shulman,et al.  Resistance to High-Fat Diet–Induced Obesity but Exacerbated Insulin Resistance in Mice Overexpressing Preadipocyte Factor-1 (Pref-1) , 2008, Diabetes.

[6]  M. Kassem,et al.  Demonstration of the presence of independent pre-osteoblastic and pre-adipocytic cell populations in bone marrow-derived mesenchymal stem cells. , 2008, Bone.

[7]  Bess Dawson-Hughes,et al.  Precision and stability of dual-energy X-ray absorptiometry measurements , 1991, Calcified Tissue International.

[8]  S. B. Heymsfield,et al.  MRI-measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women , 2007, Osteoporosis International.

[9]  Deborah R. Glasofer,et al.  Body fat redistribution after weight gain in women with anorexia nervosa. , 2005, The American journal of clinical nutrition.

[10]  A. Klibanski,et al.  Medical findings in outpatients with anorexia nervosa. , 2005, Archives of internal medicine.

[11]  T. Jensen,et al.  Regulation of Human Skeletal Stem Cells Differentiation by Dlk1/Pref‐1 , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[12]  L. Mosekilde,et al.  Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis , 2004, Biogerontology.

[13]  C. S. Lin,et al.  Potential value of vertebral proton MR spectroscopy in determining bone weakness. , 2001, AJNR. American journal of neuroradiology.

[14]  A. Klibanski,et al.  Changes in regional fat redistribution and the effects of estrogen during spontaneous weight gain in women with anorexia nervosa. , 2001, The American journal of clinical nutrition.

[15]  A. Klibanski,et al.  The effects of anorexia nervosa on bone metabolism in female adolescents. , 1999, The Journal of clinical endocrinology and metabolism.

[16]  L. Melton,et al.  Long-term fracture risk among women with anorexia nervosa: a population-based cohort study. , 1999, Mayo Clinic proceedings.

[17]  J. Treasure,et al.  Dissociation of Bone Turnover in Anorexia Nervosa , 1998, Annals of clinical biochemistry.

[18]  D. Ducassou,et al.  Comparison of two Hologic DXA systems (QDR 1000 and QDR 4500/A). , 1997, The British journal of radiology.

[19]  A. Klibanski,et al.  Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. , 1996, The Journal of clinical endocrinology and metabolism.

[20]  N. Rigotti,et al.  The clinical course of osteoporosis in anorexia nervosa. A longitudinal study of cortical bone mass. , 1991, Journal of the American Medical Association (JAMA).

[21]  W. O'Fallon,et al.  50-year trends in the incidence of anorexia nervosa in Rochester, Minn.: a population-based study. , 1991, The American journal of psychiatry.

[22]  W. Alexander,et al.  The American society for bone and mineral research , 1987, Steroids.

[23]  D. Yurgelun-Todd,et al.  Prevalence of anorexia nervosa and bulimia in three student populations , 1984 .