Skeletal glucocorticoid signalling determines leptin resistance and obesity in aging mice.
Level 5 - mechanism / opinion, no new human data
Bench and animal research (transgenic mouse model) with no human subjects.
PubMed 33045434 · doi:10.1016/j.molmet.2020.101098
What was done
Transgenic mice lacking glucocorticoid signaling in osteoblasts and osteocytes (HSD2 OB/OCY -tg) and wild-type littermates were studied longitudinally at 3, 6, 12, and 18 months of age. The researchers assessed body composition, adipose morphology, skeletal gene expression, glucose and insulin tolerance, leptin sensitivity (via arcuate nucleus STAT3 phosphorylation and feeding inhibition), sympathetic outflow markers (tyrosine hydroxylase expression), adipose tissue oxygen consumption rate, and tissue-specific glucose uptake.
What was found
Wild-type mice developed obesity, insulin resistance, and leptin resistance starting at 6 months of age, alongside reduced hypothalamic and adipose tyrosine hydroxylase expression and progressive declines in adipose oxygen consumption. In contrast, HSD2 OB/OCY -tg mice remained lean, insulin-sensitive, and leptin-sensitive up to 18 months of age. At 18 months, adipose tissue glucose uptake was 3.7-fold higher in HSD2 OB/OCY -tg mice compared with wild-type mice.
Why it matters
The study identifies skeletal glucocorticoid signaling as a key upstream driver of systemic leptin resistance and age-associated metabolic decline in mice, implicating bone tissue directly in body weight regulation.
Limits
The study is restricted to animal models; relevance to human metabolic aging is not established. Sample sizes (n) and the sex distribution of the mice are not reported in the abstract.
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