Obesity induced insulin resistance and oxidative stress in mice fed a high fat diet

Abstract

Insulin resistance (IR) is a common feature in obesity. There is a growing body of evidence linking the induction of obesity-related IR to an increase in oxidative stress. Objective: To determine if a high fat diet can induce IR and oxidative stress in a mouse model. To determine if there is an increase in oxidative stress related to adipocyte differentiation. Methods: Male mice (C57B6) were fed a high fat diet (HF) (45% kcal) or a control fed diet (CF) (10% kcal) ad libidum for 6 wk. IR was measured using an intraperitoneal glucose tolerance test. Oxidative stress was measured using thiol redox status in mouse plasma (Cys/CySS) and in differentiated and undifferentiated murine 3T3L1 cells (GSH/GSSG). Results: HF mice were significantly heavier than CF (p<.05). HF mice exhibited hyperglycemia (162±15) vs CF (82±7 mg/dL), as well as glucose intolerance (p<.05). HF mice had a 10 mv increase in plasma oxidation as compared to CF (p<.05). Cellular thiol redox in differentiated 3T3L1 cells was significantly higher (20 mv) than in undifferentiated cells. Conclusion: In this study we demonstrated that HF mice have increased IR and oxidative stress. We also showed that differentiation induces an increase in oxidative stress. This data suggests that oxidative stress and IR occur with increased adiposity. Further studies should determine mechanisms by which oxidative stress plays a role in obesity-induced IR.