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Aroor 2015 Diabetes
Coupling states ET  + , LEAK  + , OXPHOS  + , ROUTINE  +
Diseases Diabetes  +
Has abstract Novel therapies are needed for treating th
Novel therapies are needed for treating the increasing prevalence of hepatic steatosis in western populations. In this regard, dipeptidyl peptidase-4 (DPP-4) inhibitors have recently been reported to attenuate the development of hepatic steatosis, but the potential mechanisms remain poorly defined. In the current study, four week old C57Bl/6 mice were fed a high fat/high fructose western diet (WD) or WD containing DPP-4 inhibitor, MK0626, for 16 weeks. The DPP-4 inhibitor prevented WD-induced hepatic steatosis and reduced hepatic insulin resistance by enhancing insulin suppression of hepatic glucose output. WD-induced accumulation of hepatic triacylglycerol (TAG) and diacylglycerol (DAG) content was significantly attenuated with DPP-4 inhibitor treatment. In addition, MK0626 significantly reduced mitochondrial incomplete palmitate oxidation and increased indices of pyruvate dehydrogenase activity, TCA cycle flux, and hepatic TAG secretion. Furthermore, DPP4-inhibition rescued WD-induced decreases in hepatic PGC-1α and CPT-1 mRNA expression and hepatic Sirt1 protein content. Moreover, plasma uric acid levels in WD fed mice were decreased after MK0626 treatment. These studies suggest that DPP-4 inhibition ameliorates hepatic steatosis and insulin resistance by suppressing hepatic TAG and DAG accumulation through enhanced mitochondrial carbohydrate utilization and hepatic TAG secretion/export with concomitant reduction of uric acid production.
omitant reduction of uric acid production.  +
Has info [ PMID:25605806]  +
Has publicationkeywords Hepatic insulin resistance  + , Lipidomics  + , MK-0626 (DPP-4 inhibitor)  + , NAFLD  + , Obesity  +
Has title Aroor AR, Habibi J, Ford DA, Nistala R, La
Aroor AR, Habibi J, Ford DA, Nistala R, Lastra G, Manrique C, Dunham MM, Ford KD, Thyfault JP, Parks EJ, Sowers JR, Rector RS (2015) Dipeptidyl peptidase-4 inhibition ameliorates western diet-induced hepatic steatosis and insulin resistance through hepatic lipid remodeling and modulation of hepatic mitochondrial function. Diabetes 64:1988-2001.
chondrial function. Diabetes 64:1988-2001.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Exercise physiology;nutrition;life style  + , Pharmacology;toxicology  + , Respiration  +
Pathways F  + , N  + , NS  + , S  +
Preparation Isolated mitochondria  +
Tissue and cell Liver  +
Was published by MiPNetLab US MO Columbia Rector RS +
Was published in journal Diabetes +
Was published in year 2015  +
Was written by Aroor AR + , Habibi J + , Ford DA + , Nistala R + , Lastra G + , Manrique C + , Dunham MM + , Ford KD + , Thyfault JP + , Parks EJ + , Sowers JR + , Rector RS +
Categories Publications
Modification date
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14:16:24, 19 March 2019  +
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