Novel Adipokines and Their Role in Bone Metabolism: A Narrative Review

Fnu Deepika, Siresha Bathina, Reina Armamento-Villareal, Fnu Deepika, Siresha Bathina, Reina Armamento-Villareal

Abstract

The growing burden of obesity and osteoporosis is a major public health concern. Emerging evidence of the role of adipokines on bone metabolism has led to the discovery of novel adipokines over the last decade. Obesity is recognized as a state of adipose tissue inflammation that adversely affects bone health. Adipokines secreted from white adipose tissue (WAT) and bone marrow adipose tissue (BMAT) exerts endocrine and paracrine effects on the survival and function of osteoblasts and osteoclasts. An increase in marrow fat is implicated in osteoporosis and, hence, it is crucial to understand the complex interplay between adipocytes and bone. The objective of this review is to summarize recent advances in our understanding of the role of different adipokines on bone metabolism.

Methods: This is a comprehensive review of the literature available in PubMED and Cochrane databases, with an emphasis on the last five years using the keywords.

Results: Leptin has shown some positive effects on bone metabolism; in contrast, both adiponectin and chemerin have consistently shown a negative association with BMD. No significant association was found between resistin and BMD. Novel adipokines such as visfatin, LCN-2, Nesfatin-1, RBP-4, apelin, and vaspin have shown bone-protective and osteoanabolic properties that could be translated into therapeutic targets.

Conclusion: New evidence suggests the potential role of novel adipokines as biomarkers to predict osteoporosis risk, and as therapeutic targets for the treatment of osteoporosis.

Keywords: adipokines; bone metabolism; bone mineral density; bone turnover markers; osteoblast; osteoclast; osteoporosis.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Cross-talk between different Adipocyte derived factors and bone. The above figure illustrates PPARγ inhibition or activation along with adipocyte-derived adipokines can alter or disrupt the communication between osteoblasts and osteoclasts. Adipokines; omentin visfatin and resistin enhance osteoblast differentiation and inhibit osteoclast formation. On the contrary, adipokines; leptin, chemerin, and adiponectin abrogate osteoblast formation and, thus, resulting in alterations in the homeostasis of bone [142,143,144].
Figure 2
Figure 2
Illustrates the role of Novel adipokines role in bone metabolism. Apelin, vaspin, and Nesfatin when bound to receptors of APJ, Grp78, and Cannabinoid receptors (CR) activate Pi3k -Akt pathway and Ras pathway for subsequent osteoblast survival and RUNX2/Osterix pathway leading to bone formation. On the other hand, lipocalin (LCN2) binds to the MC4R receptor complex on OCPs, inducing the p38 MAP kinase pathway, then binds to Sp1 sites on the RANK promoter, activating RANK expression. This in turn favors osteoclast formation and bone resorption. Thus, novel adipokines mediating the crosstalk between osteoblast and osteoclast add on a new mechanism by which Osteoblast can control bone resorption [147,148,149,150].

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