Abstract
The growing prevalence of osteoporosis and obesity has enabled investigators to explore new perspectives at several levels on the genetic determinants that regulate body composition, energy homeostasis, and bone remodeling. Regulation of bone and adipose tissue begins at the level of the common mesenchymal progenitor and extends to the systematic hormonal and central neuronal control over tissue remodeling and substrate utilization. To assess this complex interaction, animal models, and recent large genome wide investigations have been the major investigational tools. In respect to animal investigations, reverse and forward genetic studies have both been widely utilized. In particular, obesity and bone QTLs have been explored in great depth in mouse studies. Environmental determinants have generally used a high fat diet and diet induced obesity to define gene × environmental interactions. In contrast, approaches to the genetics of fat and bone in humans have utilized genome wide association studies led by large consortia to catalog human genetic variation accompanied by new technologies capable of genotyping millions of single nucleotide variants (SNVs). Notwithstanding, the genetic relationship between fat and bone appears to be much more complex than anticipated and additional studies are needed to clarify that interaction.
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