Morris 2015 Abstract MiPschool Greenville 2015
|Intrinsic high aerobic capacity is associated with protection of mitochondrial respiratory capacity and decreased inflammation following chronic high-fat/high-cholesterol diet challenge.|
Event: MiPschool Greenville 2015
We previously reported a novel model in which rats were artificially selected over several generations to produce high and low capacity runners (HCR and LCR) with contrasting intrinsic aerobic capacities. This divergent aerobic capacity produces increased hepatic fatty acid oxidation (FAO), maximal mitochondrial respiratory capacity, and decreased liver triacylglycerol (TAG) accumulation in the HCR compared to LCR rats. A body of evidence suggests that a Western diet results in alterations in mitochondrial function facilitating increased oxidative stress, which can produce elevated expression of pro-inflammatory genes. Herein we examined the hypothesis that increased aerobic capacity associated with increased hepatic FAO/mitochondrial respiratory capacity of the HCR rat would protect against development of hepatic inflammation following a chronic high-fat/high-cholesterol diet challenge. HCR/LCR rats were fed open source low-fat diet (LFD, 10% fat, Research Diet) prior to initiation of a 45% fat (kcal)/1% cholesterol (gram) diet (Research Diet) for 16 weeks. Both HCR and LCR rats demonstrated increased weight gain following HFHC, with only the LCR having increased fat mass gain compared to LFD. Both strains were observed to have reduced hepatic complete FAO due to HFHC; however, HCR complete FAO was greater than LCR regardless of diet. The HFHC resulted in reduced state 3 hepatic mitochondrial respiration of glutamate and pyruvate in both strains, with LCR also having reduced state 3 respiration of palmitoyl-carnitine (L-PC). However, HCR was observed to have greater hepatic mitochondrial state 3 and uncoupled respiration of glutamate, pyruvate, and L-PC compared to LCR regardless of diet. The differences in state 3 mitochondrial respiration due to diet are inversely associated with increased mRNA expression of hepatic inflammation markers (MCP-1, TLR4, TLR2, IL-b, and F4/80). However, HCR rats on HFHC demonstrate significantly lower expression of these markers compared LCR. In conclusion, HCR rats are partially protected against chronic HFHC diet induced hepatic inflammation, which is associated with greater mitochondrial respiratory capacity compared to LCR.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Other
Organism: Rat Tissue;cell: Liver
Coupling state: OXPHOS, ET Pathway: N
1-Dept Mol Integrative Physiol; 2-KU Medical Center, Kansas City, VA Medical Center; 3-Dept Anesthesiol, Univ Michigan, MI, USA. - [email protected]