title: HCV synergizes with body weight in the promotion of insulin resistance.
abstract: Hepatitis C virus (HCV) infection appears to contribute to the development of insulin resistance (IR). Among the multiple determinants of IR, body mass index (BMI) is the most important. We investigated the contribution of HCV to BMI-associated IR using a transgenic mouse model expressing HCV core protein. Eight transgenic and five nontransgenic littermate controls were evaluated. Glucose and insulin tolerance tests (ITT) were performed on two separate occasions. Multivariate linear mixed modelling was used to evaluate and compare the effect of weight on IR between HCV core transgenic and nontransgenic controls. There were no statistically significant differences in glucose or ITT (P = 0.58 and P = 0.59, respectively) between the two groups, and no difference in median weights between transgenic and control mice (P = 0.11). However, there was greater variance in the distributions of Tg when compared to nontransgenic mice for both glucose and insulin tolerance. When evaluating this closely, a differential contribution of weight to IR curves between these groups was noted (P = 0.05). Among nontransgenic mice, IR curves for mice of different weights were comparable, however, for transgenic mice, higher weights resulted in larger levels of IR curves with slower decay. In all animals, steatosis was absent or minimal. We conclude that weight has a greater effect on IR in HCV core expressing transgenic mice than littermate controls. HCV therefore synergizes with weight in the promotion of IR. Steatosis was not a prerequisite for the development of IR, implying that HCV's effects on IR may be independent of steatosis.
authors.affiliation: Gastroenterology and Nutrition Unit, Department of Medicine, Children's Hospital Boston, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Delgado-Borrego
authors.forename: Y
authors.initials: Y
authors.lastname: Kamegaya
authors.forename: S H
authors.initials: SH
authors.lastname: Jordan
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
authors.forename: C
authors.initials: C
authors.lastname: Valim
authors.forename: R T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000818:Animals; D015992:Body Mass Index; D001835:Body Weight; D004195:Disease Models, Animal; D006526:Hepatitis C / Q000150:complications*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008822:Mice, Transgenic