Novel Endocrine Functions of Bone Marrow Fat

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Background

Bone marrow fat (BMF) is abundant in bone marrow cavity, however, the importance of bone marrow adipocytes have been ignored for a long time. ‘Filling’ was previously regarded as the main function of BMF. Although both white adipose tissue and bone have been accepted as endocrine organs, there are few concerns about BMF.

Recently, more and more researchers have tried to unravel the long-neglected role of BMF. Like the white adipose tissue, BMF could be a highly active endocrine organ. In addition, region-specific variations of BMF are demonstrated in rat, mouse and human. The distal ‘constitutive’ BMF (cBMF) is much more abundant and remains stable upon challenges. In contrast, the proximal ‘regulated’ BMF (rBMF) is much more active and could disappear in some condition. In addition to bone metabolism, BMF is also involved in energy balance, bone metastasis and hematopoiesis.

One of the most attractive functions of BMF is to act as an endocrine organ to regulate the functions of other tissues and organs. Fatty acids, adipokines such as adiponectin and leptin, as well as inflammatory factors such as TNF-α and IL-6 derived from bone marrow adipocytes may exert systemic effects. Studies have shown that patients with type 2 diabetes mellitus (T2DM) have higher levels of saturated fat in the bone marrow cavities. Patients with anorexia nervosa (AN) have lower serum leptin and insulin-like growth factor-1 (IGF1), and higher adiponectin and preadipocyte factor-1 (Pref1), but the relationship with BMF remains to be explored. The role of BMF in metabolic diseases should be systematically analyzed to better understand the endocrine functions of BMF in different pathophysiological environment.

The relationship between BMF and bone metastasis seems to be novel and interesting. Bone metastasis is frequently occurred in breast, prostate and lung cancer. So far, the mechanism is still poorly understood. ‘Seed and soil’ is traditionally used to explain this phenomenon. Breast, prostate and lung cancer cells (seeds) preferentially metastasize to bone (soils) instead of other organs and tissues. Bone acts as fertile ‘soils’ for these tumor cells. Although previous studies revealed numerous genes and cytokines related to bone metastasis, many factors are focused on the “seeds” but not the ‘soils’. Actually, BMF is the important component of the fertile ‘soils’ for tumor cells. Under the influence of lipid mobilizing factors released by the ‘seeds’, BMF releases free fatty acid and thus provides enough energy for “seeds”. More importantly, BMF could secret a series of adipokines (adiponectin and leptin, etc.) and inflammatory factors (IL-6,TFN-α, etc.) to enhance cell proliferation and inhibit apoptosis of tumor cells. In this way, BMF could support tumor cells to adhere, colonize and invade bone tissue in bone marrow microenvironment.

In this Research Topic, we welcome original articles, reviews, perspectives, method articles, case reports and hypotheses. The aim of the topic is to explore the novel endocrine functions of BMF and to deepen our understanding of BMF in energy balance, bone remodeling, bone metastasis, hematopoiesis and other endocrine aspects.

Keywords: Bone marrow fat, glucose metabolism, fat metabolism, bone turnover, bone metastasis

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