Pesta 2012 Abstract Bioblast
| Pesta D, Jamison Perry R, Zhang D, Jurczak M, Samuel V, Shulman GI (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 in the liver of the mitochondrial Indy protein (mINDY) of rats on energy and glucose metabolism assessed by a hyperinsulinemiceuglycemic clamp (HEC). Rats were fed a high fat diet (safflower diet) for 4 weeks. The treatment group (n=15) was injected 2 times per week with Indy ASO, the control group (n=15) with the same volume of saline. After 4 weeks of treatment, mINDY mRNA was reduced by 91% (p<0.001) in the treatment group. Hepatic triglycerides were reduced by 55% in mINDY ASO treated rats (57.7 vs. 31.2 mg/g liver, p<0.001). Basal glucose turnover (5.9 vs 8.4 mg/kg/min, p<0.05) as well as insulin stimulated glucose turnover (30.7 vs 34.7 mg/kg/min, p<0.1) and suppression of hepatic glucose production during HEC (19.7 vs 61.6%, p<0.05) were 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 and possibly increased peripheral energy demand in mINDY ASO treated rats. This might shift intracellular lipid storage from liver and muscle, where their accumulation impairs insulin signaling, to WAT.
Reference:
1. Birkenfeld AL, Lee HY, Guebre-Egziabher F, Alves TC, Jurczak MJ, Jornayvaz FR, Zhang D, Hsiao JJ, Martin-Montalvo A, Fischer-Rosinsky A, Spranger J, Pfeiffer AF, Jordan J, Fromm MF, Konig J, Lieske S, Carmean CM, Frederick DW, Weismann D, Knauf F, Irusta PM, De Cabo R, Helfand SL, Samuel VT, Shulman GI. Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice. Cell metabolism. Aug 3 2011;14(2):184-195.
• Keywords: Indy, ASO, citrate, mitochondria
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