Marrow adipose tissue as an inducible brown adipose tissue depot

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 649-677-Adipocyte Biology
Basic
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-677
Casey R Doucette*, Phuong T Le and Clifford J Rosen
Maine Medical Center Research Institute, Scarborough, ME
The role of bone marrow adipose tissue (MAT) in the regulation of whole-body metabolism during stress response is not well understood. Here, we explore a potential function of MAT as an inducible brown-like fat depot in response to environmental stress, and how this may have an effect on bone homeostasis. Marrow fat is dynamic in response to metabolic stress, and MAT volume is known to increase with age, while brown adipose tissue (BAT) function is thought to decline. In this study, we hypothesized that activation of the sympathetic nervous system by acute cold exposure stimulates inducible BAT in the marrow, with a negative impact on bone. We capitalized on skeletal and metabolic differences between C3H/HeJ (C3H) and C57BL/6J (B6) mice; male C3H mice have higher bone density and greater marrow adipose tissue (MAT) volume than B6. We studied the effect of 4ºC exposure for 6 hours in 8-, 24-, and 52-week-old male mice. At baseline, male C3H mice had a lower core body temperature than B6. We also observed that the ability of C3H mice to maintain a steady core body temperature in response to cold declined with age, implicating a reduction in BAT activity. Levels of Ucp1 mRNA were unchanged in subscapular BAT depots of aged mice with cold exposure, supporting this implication. RNA isolated from whole bone with marrow from these aged mice, however, displayed drastically increased Ucp1 expression levels in C3H mice at room temperature as compared to B6 (100x, p<0.05). These levels rose even higher in C3H in response to cold (250x), suggesting that the marrow may have thermogenic properties. Expression levels of the bone formation markers Runx2 and Osteocalcin were significantly decreased (p<0.04) with cold exposure in C3H, and serum concentrations of the bone resorption marker RANKL were significantly increased (p<0.02), indicating that cold exposure has a negative effect on bone in these mice. We also noticed that, in 8-week-old mice, serum concentrations of FGF-21 increased with cold exposure in C3H (p<0.04), which supports the idea that cold exposure is altering energy status at the expense of bone, perhaps through regulation of glucose metabolism. Here, we show that activation of the sympathetic nervous system by cold challenge has strain-dependent effects on bone, and that MAT may be acting as a novel thermogenic depot when BAT function is reduced with age. Our findings suggest that changes in ambient temperature may contribute to age-related bone loss.

Nothing to Disclose: CRD, PTL, CJR

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH Grant R01AG040217 awarded to CJR, NIDDK Grant R24DK092759 awarded to CJR
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