High-Fat Diet Induces IKKβ and Reduces Insulin Sensitivity in Rats with Low Running Capacity

Rats bred for a high-capacity to run (HCR) do not develop insulin resistance on a high-fat diet (HFD) vs. those bred for a low-capacity for running (LCR). Recently, a link between obesity and insulin resistance has been established via IKKss action and IRS-1 Ser 312/307 phosphorylation. This study measured IkBα and IRS-1 pSer 307 in mixed gastrocnemius muscle in HCR and LCR rats challenged with a 12-wk HFD. HFD treatment resulted in significantly higher glucose and insulin levels in LCR vs. HCR rats. IKBα levels, an inverse indicator of IKKss activity, were lower in LCR vs. HCR rats maintained on chow diet and were reduced further following HFD in LCR rats only. IRS-1 pSer 307 in the LCR rats increased on the HFD vs. chow. We conclude that differences in glucose tolerance between LCR and HCR rats are at least partly explained by differences in IKKss activity and pSer 307 levels.