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Bone has recently emerged as a pleiotropic endocrine
organ that secretes at least two hormones, FGF23,
which regulate kidney function and osteocalcin,
which regulate glucose homeostasis.
Researchers now identified, through molecular and
genetic analyses in mice, lipocalin 2 (LCN2) as an
osteoblast-enriched, secreted protein.
Lipocalin 2 is released into the blood by
osteoblasts (the bone forming cells), crosses the
blood-brain barrier, binds to the melanocortin 4
receptor (MC4R) in the paraventricular and
ventromedial neurons of the hypothalamus, and
activates a signaling pathway that suppresses
appetite.
After a meal, Lipocalin 2 levels in the serum of
mice rapidly increase, and this increase is required
for suppression of appetite after eating.
Loss and gain-of-function experiments in mice
demonstrate that osteoblast-derived LCN2 maintains
glucose homeostasis by inducing insulin secretion
and improves glucose tolerance and insulin
sensitivity.
In addition, osteoblast-derived LCN2 inhibits
foodintake.
Study author Stavroula Kousteni, Associate Professor
of Medicine in Physiology and Cellular Biophysics of
Columbia University thinks that all hormones that
have a function in rodents also have the same
function in humans.
For Lipocalin 2, researchers show that serum levels
inversely correlate with body weight and the
long-term blood sugar marker HbA1c in type 2
diabetes mellitus patients.
Also, there is evidence in the literature that
Lipocalin 2 serum levels increase in lean humans
after a meal, just as we observed in mice.
All these observations are indication of a similar
type of regulation and function in humans.
These results identify LCN2 as a bone-derived
hormone with metabolic regulatory effects, which
suppresses appetite in a MC4R-dependent manner, and
show that the control of appetite is an endocrine
function of bone.
For more information
nature
MC4R-dependent suppression of appetite by
bone-derived lipocalin 2
Link...
Columbia University Medical Center
Department of Phisiology and Cellular Biophysics
Link...
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