1. Biochem Biophys Res Commun. 2009 Jul 31;385(3):351-6. Epub 2009 May 20.

Critical role of Kupffer cells in the management of diet-induced diabetes and
obesity.

Neyrinck AM, Cani PD, Dewulf EM, De Backer F, Bindels LB, Delzenne NM.

Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Louvain Drug
Research Institute, Université catholique de Louvain, Brussels, Belgium.

The aim of this study was to investigate the role of Kupffer cell in glucose
metabolism and hepatic insulin sensitivity in mice. Both phagocytic activity and 
secretory capacity of Kupffer cells were blunted 24h after GdCl3 administration. 
Glucose tolerance--evaluated following an oral glucose tolerance test (OGTT)--was
higher in GdCl3-treated mice whereas fasting insulinemia and HOMA-IR index
decreased. The improvement of glucose tolerance and hepatic insulin signalling
pathway after inhibition of Kupffer cells was supported by a lower hepatic
gluconeogenic enzyme expression and a higher phosphorylation of Akt upon insulin 
challenge. Moreover, fasting hyperglycemia, insulin resistance and impaired
glucose tolerance--induced by high fat (HF) diet--were improved through chronic
administration of GdCl3. Interestingly, the inhibition of Kupffer cell exerted
antiobesity effects in HF-fed mice, and lowered hepatic steatosis. Therefore,
strategies targeting Kupffer cell functions could be a promising approach to
counteract obesity and related metabolic disorders.

PMID: 19463788 [PubMed - indexed for MEDLINE]