Pesta 2012 Abstract Bioblast
| Pesta D (2012) The effect of targeted knockdown of the Indy gene on energy metabolism in rats. Mitochondr Physiol Network 17.12. |
Link: MiPNet17.12 Bioblast 2012 - Open Access
Pesta D, Jamison Perry R, Zhang D, Jurczak M, Samuel V, Shulman GI (2012)
Event: Bioblast 2012
INDY as part of the SLC13 protein family is a high-affinity di- and tricarboxylate plasma membrane transporter involved in citrate import. Besides the effect on longevity, our lab has shown that deletion of INDY repatterns energy metabolism in a way that protects mice form high fat diet induced insulin resistance 1. In the present work, we use anti-sense oligonucleotides (ASOs) to study the effects of a constitutional knock down of the mitochondrial Indy protein (mINDY) in the liver of rats on energy and glucose metabolism assessed by a hyperinsulinemic euglycemic clamp (HEC). Rats were fed a high fat diet (safflower diet) for 4 weeks. The treatment group (n=12) was injected 2 times per week with Indy ASO, the control group (n=12) with the same volume of saline. After 4 weeks of treatment, mINDY mRNA was reduced by 84% (p<0.05) in the treatment group. Hepatic triglycerides were reduced by 17% in mINDY ASO treated rats (52.1 vs. 43.1 mg/g liver, p=0.02). Basal (6.8 vs 8.6 mg/kg/min, p=0.19) as well as insulin stimulated glucose turnover (29.4 vs 35.2 mg/kg/min, p=0.07) and suppression of hepatic glucose production during HEC (32.2 vs 59.0%, p=0.14) trended higher in the mINDY ASO treated group. Peripheral glucose uptake was not different in muscle, but there was a trend of increased uptake in WAT (21.2 vs 52.3 nmol/g/min, p=0.12). These preliminary data suggest increased insulin sensitivity in mINDY ASO treated rats, possibly by shifting intracellular lipid storage from liver and muscle, where their accumulation impairs insulin signaling, to WAT.
• Keywords: Indy, ASO, citrate, mitochondria
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