Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma

• Published in: Journal of cellular physiology 2018-12, Vol.233 (12), p.9159-9166
• Main Authors: Morris, Emma V., Edwards, Claire M.
• Format: Article
• Language: English
• Subjects: Adipocytes; adipokines; Adiponectin; Adipose tissue; Body fat; Bone cancer; Bone marrow; bone marrow (BM) adipocytes; Cancer; Cardiovascular diseases; Cell migration; Cell survival; Diabetes mellitus; Epidemics; Health risk assessment; Inflammation; Leptin; Monoclonal gammopathy; Multiple myeloma; multiple myeloma (MM); Obesity; Plasma cells; Risk analysis; Risk factors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26884

Obesity has become a global epidemic influencing the establishment and progression of a wide range of diseases, such as diabetes, cardiovascular disease, and cancer. In 2016, International Agency for Research on Cancer reported that obesity is now associated with 13 different cancers, one of which is multiple myeloma (MM), a destructive cancer of plasma cells that predominantly reside in the bone marrow. Obesity is the accumulation of excess body fat, which causes metabolic, endocrine, immunologic, and inflammatory‐like changes. Obesity is usually associated with an increase in visceral and/or subcutaneous fat; however, an additional fat depot that also responds to diet‐induced changes is bone marrow adipose tissue (BMAT). There have been several studies over the past few decades that have identified BMAT as a key driver in MM progression. Adipocytes secrete numerous adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, which when secreted at normal controlled levels have protective properties. However, in obesity these levels of secretion change, coupled with an increase in adipocyte number and size causing a profound and lasting effect on the bone microenvironment, contributing to MM cell growth, survival, and migration as well as potentially fueling bone destruction. Obesity is a modifiable risk factor making it an attractive option for targeted therapy. This review discusses the link between obesity, monoclonal gammopathy of undetermined significance (a benign condition that precedes MM), and myeloma, and the contribution of key adipokines to disease establishment and progression. There is increasing evidence for an association between obesity and myeloma pathogenesis. Understanding the mechanisms by which an increase in adiposity can drive disease progression may reveal new diagnostic and/or therapeutic approaches.