Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

George 2015 Abstract MiPschool Cape Town 2015

From Bioblast
The printable version is no longer supported and may have rendering errors. Please update your browser bookmarks and please use the default browser print function instead.
Regulation of LCAD and SIRT3 activities by NAD+ in skeletal muscle of fructose-fed rats.

Link:

George S, Ojuka E (2015)

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: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

References