Insulin Resistance Precedes Liver Adaptations After One Week of Exposure to a Very High-fat Diet

Obesity is associated with poor glucose control, hepatic steatosis, and inflammation. These poor clinical outcomes are often the result of prolonged periods of obesity. It is unclear how simultaneous short-term exposure to a very high- fat (VHF) diet and exercise may impact these outcomes.
PURPOSE: To determine the effect of one week of VHF diet and/or exercise training (EX) on glucose regulation, liver adiposity, and gene expression of inflammation within the liver of mice.
METHODS: C57BL/6 male mice (6 wks old) were randomized into 4 groups (n=8/group): low-fat (LF)/sedentary (SED), LF/EX, VHF/SED, and VHF/EX. The VHF and LF diets were 60% and 10% fat, respectively. The mice were placed on the diet and exercise intervention concomitantly. Treadmill exercise was performed 5 consecutive days at 12 m/min and 5% grade for 40 min/d. Fasting plasma glucose and insulin (INS) were assessed. Homeostatic model analysis (HOMA) was used to quantify insulin resistance. Triglyceride content of the liver (liver-TG) was assessed using a microtiter procedure. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 gene expression within the liver were assessed using quantitative real-time PCR. The LF/SED group was the referent group.

RESULTS: Body weights of the VHF groups were greater than the LF groups (p<0.001) after the one week diet intervention. Mice in the VHF groups had greater fasting INS and HOMA (p<0.05), while glucose concentrations were similar between dietary groups (p=0.075). No differences were observed between VHF diet and LF diet for liver-TG (p=0.375) or gene expression of TNF-α (p=0.072) within the liver. Exercise training reduced hepatic gene expression of IL-6 (p<0.05). No interactions between diet and exercise were observed for any variable (p>0.05).
CONCLUSION: Mice exposed to a VHF diet for one week exhibited insulin resistance without increased liver adiposity or upregulation of inflammatory markers, suggesting that short term exposure to very high fat diets quickly alters glucose regulation prior to alterations in liver inflammatory markers. Yet, this low volume of exercise stimulus appeared to begin countering some of the "proinflammatory" effects of the VHF diet, which needs further study.