Document Detail

The lipocalin-type prostaglandin D2 synthase knockout mouse model of insulin resistance and obesity demonstrates early hypothalamic-pituitary-adrenal axis hyperactivity.
MedLine Citation:
PMID:  23151358     Owner:  NLM     Status:  MEDLINE    
Obesity and diabetes are closely associated with hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the diet-induced obese C57BL/6 mouse was used to test the hypothesis that chronically elevated metabolic parameters associated with the development of obesity such as cholesterol and glucose can aggravate basal HPA axis activity. Because the lipocalin-type prostaglandin D(2) synthase (L-PGDS) knockout (KO) mouse is a model of accelerated insulin resistance, glucose intolerance, and obesity, it was further hypothesized that HPA activity would be greater in this model. Starting at 8 weeks of age, the L-PGDS KO and C57BL/6 mice were maintained on a low-fat or high-fat diet. After 20 or 37 weeks, fasting metabolic parameters and basal HPA axis hormones were measured and compared between genotypes. Correlation analyses were performed to identify associations between obesity-related chronic metabolic changes and changes in the basal activity of the HPA axis. Our results have identified strong positive correlations between total cholesterol, LDL-cholesterol, glucose, and HPA axis hormones that increase with age in the C57BL/6 mice. These data confirm that obesity-related elevations in cholesterol and glucose can heighten basal HPA activity. Additionally, the L-PGDS KO mice show early elevations in HPA activity with no age-related changes relative to the C57BL/6 mice.
Jodi F Evans; Shahidul Islam; Yoshihiro Urade; Naomi Eguchi; Louis Ragolia
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-18
Journal Detail:
Title:  The Journal of endocrinology     Volume:  216     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-03-11     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  169-80     Citation Subset:  IM    
Biomedical Research Core, Winthrop University Hospital, 222 Station Plaza North, Suite 505-B, Mineola, New York 11501, USA.
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MeSH Terms
Adrenocorticotropic Hormone / blood
Corticosterone / blood
Hypercholesterolemia / genetics,  metabolism
Hyperglycemia / genetics,  metabolism
Hypothalamo-Hypophyseal System / metabolism*
Insulin Resistance / genetics,  physiology*
Intramolecular Oxidoreductases / genetics,  metabolism*
Leptin / blood
Lipocalins / genetics,  metabolism*
Metabolic Syndrome X / genetics,  metabolism
Mice, Inbred C57BL
Mice, Knockout
Obesity / genetics,  metabolism*
Pituitary-Adrenal System / metabolism*
Grant Support
Reg. No./Substance:
0/Leptin; 0/Lipocalins; 50-22-6/Corticosterone; 9002-60-2/Adrenocorticotropic Hormone; EC 5.3.-/Intramolecular Oxidoreductases; EC R2 D-isomerase

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