Format

Send to

Choose Destination
Free Radic Biol Med. 2018 Jan;114:122-130. doi: 10.1016/j.freeradbiomed.2017.09.021. Epub 2017 Sep 25.

Increased levels of inflammatory plasma markers and obesity risk in a mouse model of Down syndrome.

Author information

1
Cellular & Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
2
INSERM U1016, Cochin Institute, Paris, France; CNRS UMR 8104, Paris, France; University of Paris Descartes, Sorbonne Paris Cité, Paris, France.
3
Université Paris Diderot, Sorbonne Paris Cité, Unité Biologie Fonctionnelle et Adaptative - CNRS UMR 8251, Paris, France.
4
Université Paris Diderot, Sorbonne Paris Cité, Unité Biologie Fonctionnelle et Adaptative - CNRS UMR 8251, Paris, France; Université Paris Sud, France.
5
Cellular & Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain. Electronic address: mara.dierssen@crg.eu.

Abstract

Down syndrome (DS) is caused by the trisomy of human chromosome 21 and is the most common genetic cause of intellectual disability. In addition to the intellectual deficiencies and physical anomalies, DS individuals present a higher prevalence of obesity and subsequent metabolic disorders than healthy adults. There is increasing evidence from both clinical and experimental studies indicating the association of visceral obesity with a pro-inflammatory status and recent studies have reported that obese people with DS suffer from low-grade systemic inflammation. However, the link between adiposity and inflammation has not been explored in DS. Here we used Ts65Dn mice, a validated DS mouse model, for the study of obesity-related inflammatory markers. Ts65Dn mice presented increased energy intake, and a positive energy balance leading to increased adiposity (fat mass per body weight), but did not show overweight, which only was apparent upon high fat diet induced obesity. Trisomic mice also had fasting hyperglycemia and hypoinsulinemia, and normal incretin levels. Those trisomy-associated changes were accompanied by reduced ghrelin plasma levels and slightly but not significantly increased leptin levels. Upon a glucose load, Ts65Dn mice showed normal increase of incretins accompanied by over-responses of leptin and resistin, while maintaining the hyperglycemic and hypoinsulinemic phenotype. These changes in the adipoinsular axis were accompanied by increased plasma levels of inflammatory biomarkers previously correlated with obesity galectin-3 and HSP72, and reduced IL-6. Taken together, these results suggest that increased adiposity, and pro-inflammatory adipokines leading to low-grade inflammation are important players in the propensity to obesity in DS. We conclude that DS would be a case of impaired metabolic-inflammatory axis.

KEYWORDS:

Down syndrome; Galectin-3; Ghrelin; HSP72; Inflammation; Interleukin-6; Leptin; Obesity; Resistin

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center