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| Status |
Public on Nov 09, 2020 |
| Title |
Skeletal glucocorticoid signaling determines aging-related leptin resistance and obesity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Aging contributes to many chronic conditions, including central obesity, insulin resistance and osteoporosis, which are also critical features of glucocorticoid excess. To investigate tissue-specific sites of glucocorticoid (GC) action during aging, we disrupted GC signalling in mouse osteoblasts via transgenic overexpression of the GC-inactivating enzyme, 11β-hydroxysteroid-dehydrogenase type 2 (11β-HSD2). Wild-type mice with intact osteoblastic GC signalling developed leptin resistance, obesity and insulin resistance with aging. In contrast, transgenic (HSD2OB-tg) mice remained lean and leptin-sensitive, and were protected against aging-related hyperinsulinaemia, blunted sympathetic responses and loss of thermogenic adipose tissue. These salutary effects were independent of the osteoblast-derived factors osteocalcin and lipocalin-2. Gene expression analysis of bones from HSD2OB-tg mice indicated an early induction of pro-osteogenic and anti-adipogenic factors, and activation of a local pro-inflammatory TLR4-ZBTB16-NR1H3 network in osteoblastic cells. These findings reveal a critical role for skeletal glucocorticoid signaling in central leptin action, and in impaired metabolic function with aging
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| Overall design |
Wild-type and HSD2^OB-tg mice were housed under standard laboratory conditions at 24°C on a 12:12 h light–dark cycle with free access to standard chow and water. Mice were sacrificed at 3, 6, 12 and 18 m of age for females and 3 and 18 m of age for males. Food intake was determined every 4 to 6 wks. Total RNA extracted from tibiae and femur of 3, 6, 12, and 18 months old WT vs HSD2^ob-tg mice were interrogated using Affymetrix Mouse GeneChip Gene 2.1 ST arrays. Biological triplicates were investigated.
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| Contributor(s) |
Henneicke H, Lin RC, Swarbrick M, Zhou H, Siebel MJ |
| Citation(s) |
33045434 |
| Submission date |
Dec 04, 2019 |
| Last update date |
Nov 09, 2020 |
| Contact name |
Ruby CY Lin |
| E-mail(s) |
rubyl@unsw.edu.au, ruby.lin@sydney.edu.au
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| Organization name |
The Westmead Institute for Medical Research
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| Street address |
176 Hawkesbury Road, Westmead
|
| City |
Sydney |
| State/province |
NSW |
| ZIP/Postal code |
2145 |
| Country |
Australia |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA593512 |
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