Aerobic capacity and hepatic mitochondrial lipid oxidation alters susceptibility for chronic high-fat diet-induced hepatic steatosis.
Rats selectively bred for high capacity running (HCR) or low capacity running (LCR) display divergence for intrinsic aerobic capacity and hepatic mitochondrial oxidative capacity, both factors associated with susceptibility for nonalcoholic fatty liver disease. Here, we tested if HCR and LCR rats display differences in susceptibility for hepatic steatosis after 16 wk of high-fat diets (HFD) with either 45% or 60% of kcals from fat. HCR rats were protected against HFD-induced hepatic steatosis, whereas only the 60% HFD induced steatosis in LCR rats, as marked by a doubling of liver triglycerides. Hepatic complete fatty acid oxidation (FAO) and mitochondrial respiratory capacity were all lower in LCR compared with HCR rats. LCR rats also displayed lower hepatic complete and incomplete FAO in the presence of etomoxir, suggesting a reduced role for noncarnitine palmitoyltransferase-1-mediated lipid catabolism in LCR versus HCR rats. Hepatic complete FAO and mitochondrial respiration were largely unaffected by either chronic HFD; however, 60% HFD feeding markedly reduced 2-pyruvate oxidation, a marker of tricarboxylic acid (TCA) cycle flux, and mitochondrial complete FAO only in LCR rats. LCR rats displayed lower levels of hepatic long-chain acylcarnitines than HCR rats but maintained similar levels of hepatic acetyl-carnitine levels, further supporting lower rates of β-oxidation, and TCA cycle flux in LCR than HCR rats. Finally, only LCR rats displayed early reductions in TCA cycle genes after the acute initiation of a HFD. In conclusion, intrinsically high aerobic capacity confers protection against HFD-induced hepatic steatosis through elevated hepatic mitochondrial oxidative capacity.
Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas.
E Matthew
EM
Morris
Medicine and Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri.
Grace M E
GM
Meers
Anesthesiology, University of Michigan, Ann Arbor, Michigan.
Lauren G
LG
Koch
Anesthesiology, University of Michigan, Ann Arbor, Michigan.
Steven L
SL
Britton
Pharmacology and Advanced Imaging Research, University of Texas Southwestern, Dallas, Texas.
Justin A
JA
Fletcher
Pharmacology and Advanced Imaging Research, University of Texas Southwestern, Dallas, Texas.
Xiaorong
X
Fu
Arkansas Children's Nutrition Center and the Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Kartik
K
Shankar
Pharmacology and Advanced Imaging Research, University of Texas Southwestern, Dallas, Texas.
Shawn C
SC
Burgess
Medicine and Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri.
Jamal A
JA
Ibdah
Medicine and Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri; Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; Research Service, Harry S. Truman Memorial Veterans Affairs Hospital, Columbia, Missouri.
R Scott
RS
Rector
Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas; Research Service, Kansas City Veterans Affairs Medical Center, Kansas City, Missourit; and jthyfault@kumc.edu.
John P
JP
Thyfault
D000332:Aerobiosis; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D059305:Diet, High-Fat; D004198:Disease Susceptibility; D005227:Fatty Acids / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D014280:Triglycerides; C116917:acylcarnitine; D019289:Pyruvic Acid; D002331:Carnitine
acylcarnitines; exercise; fat oxidation; fatty liver; fitness