Cooper 2018 Exp Physiol

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Cooper MA, McCoin C, Pei D, Thyfault JP, Koestler D, Wright DE (2018) Reduced mitochondrial reactive oxygen species production in peripheral nerves of mice fed a ketogenic diet. Exp Physiol 103:1206-12.

» PMID: 30088302

Cooper MA, McCoin C, Pei D, Thyfault JP, Koestler D, Wright DE (2018) Exp Physiol

Abstract: Metabolic syndrome and obesity are increasing epidemics that significantly impact the peripheral nervous system and lead to negative changes in sensation and peripheral nerve function. Research to understand the consequences of diet, obesity and fuel usage in sensory neurons has commonly focused on glucose metabolism. Here, we tested whether mouse sensory neurons and nerves have the capacity to metabolize fat-based fuels (palmitoyl-CoA) and whether these effects are altered by feeding of a ketogenic (90% kcal fat) diet compared with a control diet (14% kcal fat). Male C57Bl/6 mice were placed on the diets for 10 weeks, and after the mice were killed, the dorsal root ganglion (DRG) and sciatic nerve (SN) were placed in an Oroboros oxygraph-2K to examine diet-induced alterations in metabolism (respiration) of palmitoyl-CoA and H2O2 emission (fluorescence). In addition, RNAseq was performed on the DRG of mice fed a control or a ketogenic diet for 12 weeks, and genes associated with mitochondrial respiratory function were analysed. Our results suggest that the sciatic nerves from mice fed a ketogenic diet display reduced O2 respiration and H2O2 emission when metabolizing palmitoyl-CoA compared with mice fed a control diet. Assessments of changes in mRNA gene expression reveal alterations in genes encoding the NADH dehydrogenase complex and complex IV, which could alter production of reactive oxygen species. These new findings highlight the ability of sensory neurons and axons to oxidize fat-based fuel sources and show that these mechanisms are adaptable to dietary changes.

© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

Keywords: Dorsal root ganglion, Fat, Ketogenic, Metabolism, Mitochondria, Sciatic nerve Bioblast editor: Plangger M O2k-Network Lab: US KS Kansas City Thyfault JP


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes, Obesity 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Permeabilized tissue 

Regulation: Fatty acid  Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, NS  HRR: Oxygraph-2k, O2k-Fluorometer 

2018-09, Amplex UltraRed