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{{Abstract | {{Abstract | ||
|title=Regulation of LCAD and SIRT3 activities by NAD+ in skeletal muscle of fructose-fed rats. | |||
|authors=George S, Ojuka E | |||
|year=2015 | |year=2015 | ||
|event=MiPschool Cape Town 2015 | |event=MiPschool Cape Town 2015 | ||
|abstract=Excess fructose consumption has been shown to mediate mitochondrial | |||
β-oxidation dysfunction in skeletal muscle, resulting in decreased fattyacid | |||
mediated respiration and elevated levels of long chain acylcarnitine | |||
intermediates [1]. It has been observed that fructose decreases the | |||
expression of LCAD (long chain acyl-CoA dehydrogenase) [2], the rate | |||
limiting enzyme in β-oxidation, and of SIRT3 (the NAD+-dependent | |||
deacetylase that regulates the activity of LCAD) [1]. Regular exercise | |||
has been shown to restore mitochondrial function, including β-oxidation, | |||
and improve insulin sensitivity in type-2 diabetics. Studies in mice and | |||
rats have found that exercise increases NAD+ levels (3), SIRT3 levels | |||
(4) and fatty acid oxidation (5). These observations suggest that a) the | |||
fructose-induced dysfunction in β-oxidation might be due to its effect | |||
on the NADH/NAD+ ratio in cells and b) a program of exercise might | |||
ameliorate the effects of fructose on β-oxidation. Therefore, the proposed study aims to test the following hypotheses: a) Fructose-induced | |||
decline in LCAD and SIRT3 activities results from decreased NAD+ | |||
levels. b) Regular exercise will ameliorate fructose-induced β-oxidation | |||
dysfunction in skeletal muscle by augmenting LCAD and SIRT3 activities | |||
as well as NAD+ content. c) Improvements in β-oxidation, SIRT3 activity | |||
and LCAD function by exercise result from increased NAD+ levels in | |||
cells. A rat model will be used to test these hypotheses. Rats will be | |||
randomly placed in one of the following treatment groups for 8 weeks: | |||
a) no treatment (control), b) 10% fructose water, c) 10% fructose + | |||
nicotidamide ribosome (an NAD+-boosting agent), d) 10% fructose + | |||
exercise, e) 10% fructose + exercise + FK866 (an inhibitor of the NAD+ | |||
salvage pathway) f) exercise, g) 10% glucose. All rats will receive chow | |||
and water ad libitum. The following parameters will be measured: a) | |||
abdominal fat weight, b) plasma free fatty acids, insulin, and glucose | |||
levels, c) acylcarnitine levels in blood and skeletal muscle by ESI-MS/ | |||
MS, and d) mitochondrial β-oxidation in permeabilized skeletal muscle | |||
fibres using high-resolution respirometry with long chain acylcarnitines | |||
+ malate as substrates. In addition, the activities and/or levels of LCAD, | |||
SIRT3, Citrate Synthase and NADH/NAD+ will be measured. | |||
|mipnetlab=ZA Cape Town Smith J, O2k-Network Manager South Africa, ZA Cape Town Ojuka EO | |||
}} | }} | ||
{{Labeling}} | {{Labeling | ||
|area=Exercise physiology;nutrition;life style | |||
|organism=Rat | |||
|tissues=Skeletal muscle | |||
|preparations=Permeabilized tissue | |||
|pathways=N | |||
|instruments=Oxygraph-2k | |||
}} | |||
== Affiliations == | |||
UCT/MRC Research Unit Exercise Sc & Sports Medicine, | |||
Dept Human Biol | |||
Univ Cape Town, Sport Science, South Africa. - GRGSID001@myuct.ac.za | |||
== References == |
Latest revision as of 16:16, 26 March 2018
Regulation of LCAD and SIRT3 activities by NAD+ in skeletal muscle of fructose-fed rats. |
Link:
Event: MiPschool Cape Town 2015
Excess fructose consumption has been shown to mediate mitochondrial β-oxidation dysfunction in skeletal muscle, resulting in decreased fattyacid mediated respiration and elevated levels of long chain acylcarnitine intermediates [1]. It has been observed that fructose decreases the expression of LCAD (long chain acyl-CoA dehydrogenase) [2], the rate limiting enzyme in β-oxidation, and of SIRT3 (the NAD+-dependent deacetylase that regulates the activity of LCAD) [1]. Regular exercise has been shown to restore mitochondrial function, including β-oxidation, and improve insulin sensitivity in type-2 diabetics. Studies in mice and rats have found that exercise increases NAD+ levels (3), SIRT3 levels (4) and fatty acid oxidation (5). These observations suggest that a) the fructose-induced dysfunction in β-oxidation might be due to its effect on the NADH/NAD+ ratio in cells and b) a program of exercise might ameliorate the effects of fructose on β-oxidation. Therefore, the proposed study aims to test the following hypotheses: a) Fructose-induced decline in LCAD and SIRT3 activities results from decreased NAD+ levels. b) Regular exercise will ameliorate fructose-induced β-oxidation dysfunction in skeletal muscle by augmenting LCAD and SIRT3 activities as well as NAD+ content. c) Improvements in β-oxidation, SIRT3 activity and LCAD function by exercise result from increased NAD+ levels in cells. A rat model will be used to test these hypotheses. Rats will be randomly placed in one of the following treatment groups for 8 weeks: a) no treatment (control), b) 10% fructose water, c) 10% fructose + nicotidamide ribosome (an NAD+-boosting agent), d) 10% fructose + exercise, e) 10% fructose + exercise + FK866 (an inhibitor of the NAD+ salvage pathway) f) exercise, g) 10% glucose. All rats will receive chow and water ad libitum. The following parameters will be measured: a) abdominal fat weight, b) plasma free fatty acids, insulin, and glucose levels, c) acylcarnitine levels in blood and skeletal muscle by ESI-MS/ MS, and d) mitochondrial β-oxidation in permeabilized skeletal muscle fibres using high-resolution respirometry with long chain acylcarnitines + malate as substrates. In addition, the activities and/or levels of LCAD, SIRT3, Citrate Synthase and NADH/NAD+ will be measured.
• O2k-Network Lab: ZA Cape Town Smith J, O2k-Network Manager South Africa, ZA Cape Town Ojuka EO
Labels: MiParea: Exercise physiology;nutrition;life style
Organism: Rat
Tissue;cell: Skeletal muscle
Preparation: Permeabilized tissue
Pathway: N HRR: Oxygraph-2k
Affiliations
UCT/MRC Research Unit Exercise Sc & Sports Medicine, Dept Human Biol Univ Cape Town, Sport Science, South Africa. - GRGSID001@myuct.ac.za