Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice

Maria Razzoli, Jacob McCallum, Allison Gurney, William C. Engeland, Alessandro Bartolomucci

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Genetic predisposition and environmental challenges interact to determine individual vulnerability to obesity and type 2 diabetes. We previously established a mouse model of chronic subordination stress-induced hyperphagia, obesity, metabolic like-syndrome and insulin resistance in the presence of a high-fat diet. However, it remains to be established if social stress could also aggravate glucose intolerance in subjects genetically predisposed to develop obesity and type 2 diabetes. To answer this question, we subjected genetically obese mice due to deficiency of the leptin receptor (db/db strain) to chronic subordination stress. Over five weeks, subordination stress in db/db mice led to persistent hyperphagia, hyperglycemia and exacerbated glucose intolerance altogether suggestive of an aggravated disorder when compared to controls. On the contrary, body weight and fat mass were similarly affected in stressed and control mice likely due to the hyperactivity shown by subordinate mice. Stressed db/db mice also showed increased plasma inflammatory markers. Altogether our results suggest that chronic stress can aggravate glucose intolerance but not obesity in genetically predisposed subjects on the basis of a disrupted leptin circuitry.

Original languageEnglish (US)
JournalGenes and Nutrition
Issue number3
StatePublished - May 2015

Bibliographical note

Funding Information:
Acknowledgments The authors wish to thank Marina Yoder for technical assistance in the conduct of the corticosterone radio-immuno-assay. This work was supported by U of MN Medical School to AB and by NSF IOS1025199 to WCE.

Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.


  • Corticosterone
  • Metabolic function
  • Social defeat
  • Subordination


Dive into the research topics of 'Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice'. Together they form a unique fingerprint.

Cite this