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Physiological and metabolic characteristics of novel double-mutant female mice with targeted disruption of both growth hormone-releasing hormone and growth hormone receptor
- Source :
- Aging Cell
- Publication Year :
- 2020
-
Abstract
- Mice with disruptions of growth hormone‐releasing hormone (GHRH) or growth hormone receptor (GHR) exhibit similar phenotypes of prolonged lifespan and delayed age‐related diseases. However, these two models respond differently to calorie restriction indicating that they might carry different and/or independent mechanisms for improved longevity and healthspan. In order to elucidate these mechanisms, we generated GHRH and GHR double‐knockout mice (D‐KO). In the present study, we focused specifically on the characteristics of female D‐KO mice. The D‐KO mice have reduced body weight and enhanced insulin sensitivity compared to wild‐type (WT) controls. Growth retardation in D‐KO mice is accompanied by decreased GH expression in pituitary, decreased circulating IGF‐1, increased high‐molecular‐weight (HMW) adiponectin, and leptin hormones compared to WT controls. Generalized linear model‐based regression analysis, which controls for body weight differences between D‐KO and WT groups, shows that D‐KO mice have decreased lean mass, bone mineral density, and bone mineral content, but increased adiposity. Indirect calorimetry markers including oxygen consumption, carbon dioxide production, and energy expenditure were significantly lower in D‐KO mice relative to the controls. In comparison with WT mice, the D‐KO mice displayed reduced respiratory exchange ratio (RER) values only during the light cycle, suggesting a circadian‐related metabolic shift toward fat utilization. Interestingly, to date survival data suggest extended lifespan in D‐KO female mice.<br />In comparison with WT mice, the D‐KO mice displayed reduced respiratory exchange ratio (RER) values only during the light cycle, suggesting a circadian‐related metabolic shift towards fat utilization.
- Subjects :
- 0301 basic medicine
Leptin
medicine.medical_specialty
Aging
Calorie restriction
Longevity
Growth hormone receptor
Biology
Growth Hormone-Releasing Hormone
GHR
03 medical and health sciences
Gene Knockout Techniques
Mice
0302 clinical medicine
Oxygen Consumption
GHRH
Internal medicine
medicine
Animals
insulin sensitivity
Insulin-Like Growth Factor I
Respiratory exchange ratio
Adiposity
Caloric Restriction
Gene Editing
Mice, Knockout
indirect calorimetry
Adiponectin
Body Weight
Cell Biology
Receptors, Somatotropin
Carbon Dioxide
Growth hormone–releasing hormone
030104 developmental biology
Endocrinology
Growth Hormone
CRISPR
Lean body mass
Female
Original Article
Energy Metabolism
metabolism
030217 neurology & neurosurgery
Hormone
Signal Transduction
Subjects
Details
- ISSN :
- 14749726
- Volume :
- 20
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Aging cell
- Accession number :
- edsair.doi.dedup.....b6aed77c422399e25c359fbde38be86c