Aroor 2015 Diabetes
| 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. |
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) Diabetes
Abstract: 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-1Ξ± 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. β’ Keywords: Lipidomics, NAFLD, Obesity, Hepatic insulin resistance, MK-0626 (DPP-4 inhibitor)
β’ O2k-Network Lab: US MO Columbia Rector RS
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, Pharmacology;toxicology
Pathology: Diabetes
Organism: Mouse Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: LEAK, ROUTINE, OXPHOS, ET
Pathway: F, N, S, NS
HRR: Oxygraph-2k
MitoFit news 2015#12
- 2015-07-16: High fat/high fructose and modulation of hepatic mitochondrial function. Β» MitoFit news
