Low aerobic capacity and high-fat diet contribute to oxidative stress and IRS-1 degradation in the kidney.
OBJECTIVE
Insulin receptor (IR-alpha and IR-beta) is reduced in the kidney of insulin-resistant rodents. It is unknown if there are also reductions in insulin receptor substrate (IRS)-1 or if these effects are due to metabolic injury. Thereby, we hypothesized intrinsically high aerobic fitness would protect against high-fat diet (HFD)-induced reactive oxygen species (ROS) and IRS-1 degradation.


METHODS
We investigated the effects of HFD on triglyceride content, ROS production and IRS-1 degradation in the kidney of high-capacity (HCR)/low-capacity (LCR) rats, a model of intrinsic high and low aerobic capacity. Eighteen-week-old HCR and LCR rats were placed on a HFD or normal chow diet for 7 weeks. Intraperitoneal glucose tolerance, ROS, IR-beta, total IRS-1 and ubiquitination were measured.


RESULTS
The HCR displayed greater insulin sensitivity and were resistant to HFD-induced insulin resistance. In the LCR kidney, HFD increased ROS potential, and reduced total IR-beta and IRS-1 without altering triacylglycerol content. IRS-1 ubiquitination was higher in the LCR than HCR kidney, increased after HFD.


CONCLUSIONS
Our data support that HFD-mediated kidney ROS is associated with reductions in IRS-1 and systemic insulin resistance. Further, high intrinsic aerobic capacity protects against IRS-1 degradation in the kidney following exposure to HFD.
Morris
E Matthew
EM
Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65212, USA.
Whaley-Connell
Adam T
AT
Thyfault
John P
JP
Britton
Steven L
SL
Koch
Lauren G
LG
Wei
Yongzhong
Y
Ibdah
Jamal A
JA
Sowers
James R
JR
D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species
D004041:Dietary Fats; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D008055:Lipids; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D005947:Glucose