Difference between revisions of "Sheldon 2015 Abstract MiPschool Greenville 2015"
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{{Abstract | {{Abstract | ||
|title=Twelve weeks of treadmill training as a treatment for western diet induced NASH alters mitochondrial respiration in hyperphagic OLETF rats. | |||
|authors=Sheldon RD, Linden MA, Morris EM, Meers GM, Laughlin MH, Rector RS | |||
|year=2015 | |year=2015 | ||
|event=MiPschool Greenville 2015 | |event=MiPschool Greenville 2015 | ||
|abstract=Impairments in mitochondrial function are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the progression to nonalcoholic steatohepatitis (NASH; hepatic inflammation and fibrosis). Lifestyle interventions (diet and exercise) are among the most effective preventative measures against NAFLD, yet less is known about the propensity for exercise training to reverse established NASH. Here we tested the hypothesis that initiation of treadmill exercise training in early NASH would improve hepatic mitochondrial respiration in rats. Hyperphagic OLETF (Otsuka Long-Evans Tokushima Fatty) rats were fed a western-style diet (WD; 45% fat, 1% cholesterol, 17% sucrose) for 24-weeks. Following 12-weeks of WD, OLETF rats were randomly divided into sedentary control (SED), endurance treadmill exercise training (EX), and food restriction (FR; ~85%, to account for reduced food intake that occurs with exercise ) groups for an additional 12-weeks. Isolated hepatic mitochondrial state II and state III respiration were assessed using Clark electrodes in response to stimulation with glutamate (G; 10 mM), malate (M; 1 mM), succinate (S; 10 mM) and/or ADP (0.2 mM). Maximal uncoupled respiration was determined via 2 µM serial additions of FCCP. FR resulted in elevated state III respiration through complex I (G+M; +36%) and complex I + II (G+M+S; +39%) and maximal uncoupled respiration (+FCCP; +29%) when compared to the EX group (''p'' < 0.05) while no changes were observes versus SED. Surprisingly, State III respiration through complex I+II (G+M+S) was significantly reduced (-23%; ''p'' < 0.05) in EX versus SED rats. Finally, EX caused an increase (~10%) versus SED (''p''=) and FR in whole liver citrate synthase activity, suggesting that EX increases mitochondrial content. These data indicate that 12-weeks of treadmill exercise training with ongoing WD feeding are ineffective at improving and may further impair mitochondrial respiration in this model of NASH. Alternatively, the modest increase hepatic mitochondrial content may indicate a reduced functional need per unit of mitochondria. Future studies should address whether a synergism exists between a healthful diet and exercise training when used as a treatment paradigm for NASH. | |||
}} | |||
{{Labeling | |||
|area=Respiration, Exercise physiology;nutrition;life style | |||
|organism=Rat | |||
|preparations=Isolated mitochondria | |||
|couplingstates=LEAK, OXPHOS, ETS | |||
|substratestates=CI, CIII | |||
}} | }} | ||
== Affiliations == | == Affiliations == | ||
1- | Depts 1-Nutrition and Exercise Physiol, 2-Medicine, 3-Biomed Sci, Univ Missouri, | ||
4-Harry S Truman Memorial VA Hospital, Columbia, MO, USA. - | |||
== | == Figure 1 == | ||
# | [[Image:MiPschool2015Greenville Sheldon Figure.jpg|left|500px]] Figure 1. (A) Oxygen consumption rate in isolated hepatic mitochondria. (B) Citrate synthase activity in whole liver homogenate. *; EX different from FR, ''p'' < 0.05. #; EX different from SED, ''p'' < 0.05. | ||
Revision as of 13:56, 1 July 2015
| Twelve weeks of treadmill training as a treatment for western diet induced NASH alters mitochondrial respiration in hyperphagic OLETF rats. |
Link:
Sheldon RD, Linden MA, Morris EM, Meers GM, Laughlin MH, Rector RS (2015)
Event: MiPschool Greenville 2015
Impairments in mitochondrial function are implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the progression to nonalcoholic steatohepatitis (NASH; hepatic inflammation and fibrosis). Lifestyle interventions (diet and exercise) are among the most effective preventative measures against NAFLD, yet less is known about the propensity for exercise training to reverse established NASH. Here we tested the hypothesis that initiation of treadmill exercise training in early NASH would improve hepatic mitochondrial respiration in rats. Hyperphagic OLETF (Otsuka Long-Evans Tokushima Fatty) rats were fed a western-style diet (WD; 45% fat, 1% cholesterol, 17% sucrose) for 24-weeks. Following 12-weeks of WD, OLETF rats were randomly divided into sedentary control (SED), endurance treadmill exercise training (EX), and food restriction (FR; ~85%, to account for reduced food intake that occurs with exercise ) groups for an additional 12-weeks. Isolated hepatic mitochondrial state II and state III respiration were assessed using Clark electrodes in response to stimulation with glutamate (G; 10 mM), malate (M; 1 mM), succinate (S; 10 mM) and/or ADP (0.2 mM). Maximal uncoupled respiration was determined via 2 µM serial additions of FCCP. FR resulted in elevated state III respiration through complex I (G+M; +36%) and complex I + II (G+M+S; +39%) and maximal uncoupled respiration (+FCCP; +29%) when compared to the EX group (p < 0.05) while no changes were observes versus SED. Surprisingly, State III respiration through complex I+II (G+M+S) was significantly reduced (-23%; p < 0.05) in EX versus SED rats. Finally, EX caused an increase (~10%) versus SED (p=) and FR in whole liver citrate synthase activity, suggesting that EX increases mitochondrial content. These data indicate that 12-weeks of treadmill exercise training with ongoing WD feeding are ineffective at improving and may further impair mitochondrial respiration in this model of NASH. Alternatively, the modest increase hepatic mitochondrial content may indicate a reduced functional need per unit of mitochondria. Future studies should address whether a synergism exists between a healthful diet and exercise training when used as a treatment paradigm for NASH.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Organism: Rat
Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
Affiliations
Depts 1-Nutrition and Exercise Physiol, 2-Medicine, 3-Biomed Sci, Univ Missouri,
4-Harry S Truman Memorial VA Hospital, Columbia, MO, USA. -
Figure 1
Figure 1. (A) Oxygen consumption rate in isolated hepatic mitochondria. (B) Citrate synthase activity in whole liver homogenate. *; EX different from FR, p < 0.05. #; EX different from SED, p < 0.05.
