Aroor 2015 Diabetes: Difference between revisions
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{{Publication | {{Publication | ||
|title=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 [ | |title=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. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/25605806 PMID:25605806] | |||
|authors=Aroor AR, Habibi J, Ford DA, Nistala R, Lastra G, Manrique C, Dunham MM, Ford KD, Thyfault JP, Parks EJ, Sowers JR, Rector RS | |authors=Aroor AR, Habibi J, Ford DA, Nistala R, Lastra G, Manrique C, Dunham MM, Ford KD, Thyfault JP, Parks EJ, Sowers JR, Rector RS | ||
|year=2015 | |year=2015 | ||
|journal=Diabetes | |journal=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-1ฮฑ 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. | |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-1ฮฑ 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. | ||
|keywords=Lipidomics, NAFLD, Obesity, Hepatic insulin resistance, MK-0626 (DPP-4 inhibitor) | |||
|mipnetlab=US MO Columbia Rector RS | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Exercise physiology;nutrition;life style, | |area=Respiration, Exercise physiology;nutrition;life style, Pharmacology;toxicology | ||
|diseases=Diabetes | |||
|organism=Mouse | |organism=Mouse | ||
| | |tissues=Liver | ||
|preparations=Isolated mitochondria | |||
|couplingstates=LEAK, ROUTINE, OXPHOS, ET | |||
|pathways=F, N, S, NS | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
[[Image:Logo MitoFit.jpg|right|120px|link=http://www.mitofit.org/index.php/MitoFit|MitoFit]] | |||
== MitoFit news 2015#12 == | |||
* 2015-07-16: High fat/high fructose and modulation of hepatic mitochondrial function. ยป [[K-Regio_MitoFit#2015 |MitoFit news]] |
Latest revision as of 16:16, 19 March 2019
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-1ฮฑ 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. โข Keywords: Lipidomics, NAFLD, Obesity, Hepatic insulin resistance, MK-0626 (DPP-4 inhibitor)
โข 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. ยป MitoFit news