Diet composition influences the effect of high fat diets on bone in growing male mice

Beaver, Laura M.; Prati, Maud; Gilman, Kristy E.; Luo, Ting; Shay, Neil F.; Branscum, Adam J.; Turner, Russell T.; Iwaniec, Urszula T.

doi:10.1016/j.bone.2023.116888

Cited by 2 publications

(1 citation statement)

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“…Obesity is believed to induce excessive adipocyte accumulation not only in peripheral WAT but also in bone marrow cavities in rodents and humans, contributing to detrimental disturbances in bone remodeling or bone regeneration 2 , 27 , 28 . Since ESRRA is responsive to stress-induced metabolic challenges including overfeeding 21 , 26 , we queried whether adipocyte-specific ablation of ESRRA is resistant to diet-induced obesity (DIO) or involved in fat-bone axis.…”

Section: Resultsmentioning

confidence: 99%

Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow

Huang,

Lu,

Wang

et al. 2024

Nat Commun

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Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.

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