Tuesday, July 26, 2011

Overweight or Just "Heavy Bones"? Recent Studies Provide Insights Into How Your Bones Affect Your Metabolism

Image 1: The yellow bone marrrow fat
turns out to be more than a filler.
In Germany there is a common saying that is predominantly used by the mothers of fat kids: "My son, overweight? No. He just has some really heavy bones." Well, I guess few of these proud mothers will be aware that recent research from the Boston Medical School (Fulzele. 2011) and the University of Toledo suggests that there may be more to the bone-bodyweight connection than even they may have thought.

In a comprehensive review of the latest findings on bone metabolism (Fulzele. 2011) Keertik Fulzele and Thomas L. Clemens state that the "contemporary model [which] assigns IGFs [insulin like growth factor] as central regulators of cell profileration, survival, and organism growth" and reduces the influence of insulin to the "level of regulation fuel utilization, storage, and energy expenditure" is too simplistic to to accommodate the overlapping roles of IGF and insulin in several physiologic processes, one of which is the recently discovered and previously unappreciated skeletal action of insulin. Via skeletal insulin receptors, the latter is intricately involved in
  • osteablast [=bone cells] bone acquisition
  • osteocalcin production
Of these, the production of the noncollagenous peptide ostecalcin could be of special interest with respect to the metabolic function of bone, as its undercarboxylated form (carboxylation of osteocalcin occurs in the presence of vitamin K and "activates" the peptide hormone, so that it can fulfill its bone-building function), which has a low affinity for bone matrix, appears to function as a hormone on the systemic level. On the other hand, insulin has lately been found to increase the accumulation of undercarboxylated osteocalcin, which "in turn acts in an endocrine fashion to regulate pancreatic insulin secretion and peripheral insulin responsiveness". It is this hitherto unknown mechanism by which your bones factor in the complex hormonal game that is your metabolism and by which skeletal energy-sensing pathways may manage fuel production, storage, and expenditure in a similar vein as their analogues in muscle and fat tissue.

Figure 1: Metabolic and endocrine functions of white (WAT) and brown (BAT) adipocytes in your bone marrow
(based on Czernik. 2011)
As the scientists point out, we are just beginning to understand the sophisticated role our bones play in the orchestration of our metabolism. Questions that still have to be answered relate to the ways, osteablasts "sense" glucose and other fuels, whether they simply burn amino acids and glucose as fuel and whether and to which extent medications that influence bone resorption could also be used for blood sugar management.
Answers to these questions will expand our understanding of the biology of the skeleton and should have implications in the diagnosis and management of patients with metabolic diseases, including osteoporosis and diabetes.
More information on the underlying mechanisms by which your bones directly influence your metabolic rate, and thus your weight, can be found in a Special Issue of the Journal 'Bone', entitled "Bone and Fat". In her paper (Czernik. 2011), Beata Lecka-Czernik elaborates on the possible influence the yellow bone fat, which - believe it or not - occupies a significant portion of your bone marrow cavity, could have on your metabolism, both locally, as well as systemically.
Did you know? The fat distribution in your skeleton is site, age, and gender specific (men have more bone fat than women). In adults the bone marrow cavity of long bone, for example, is entirely filled with fat, while the ileac crest marrow contains only ~40% fat. The overall amount of bone fat can double in the course of your life and the WAT- and BAT-like adipocytes appear to have similar metabolic and endocrine functions as their white (WAT) and brown (BAT) analogues on your hips, your belly and your neck.
In this context, the integrative models of Ferron et al and Fulzele et al. are of particular interest, as they could help elucidate the link between the anabolic effects of insulin signaling in osteoblasts and the regulation of insulin sensitivity in peripheral organs. And who knows, even if its not the "heavy bones" that contribute to the obesity pandemic,"fat bones" could well become a novel target in its prevention and treatment.