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Threadmill exercise Threadmill exercise reduce reduce obestatin obestatin concentrations in rat concentrations in rat fundus and small fundus and small intestineintestine.(abbass Ghanbari-.(abbass Ghanbari-Niaki.2008Niaki.2008))

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Intruduction:Intruduction:

• Ghrelin and obestatin both are Ghrelin and obestatin both are orexigenic/anorexigenic peptides orexigenic/anorexigenic peptides which are secreted from which are secreted from gasterointestinal tracts(fondus gasterointestinal tracts(fondus submucusa cells).submucusa cells).

• Encoded by same gene.Encoded by same gene.

• Stimulate growth hormone releaseStimulate growth hormone release

• Have Have oppositeopposite actions on food intake actions on food intake

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•Ghrelin:Ghrelin:• A 28-amino acid peptide.A 28-amino acid peptide.• Novel player in the gut-brain regulation Novel player in the gut-brain regulation

of growth hormone and energy of growth hormone and energy balance.balance.

• Produced mainly by P/D1 cells lining Produced mainly by P/D1 cells lining the fundes of the human stomach and the fundes of the human stomach and epsilon cells of the pacreas thatepsilon cells of the pacreas that stimulates appetitestimulates appetite..

• Also produce in the hypothalamic Also produce in the hypothalamic arcuate nucleus which stimulate GH arcuate nucleus which stimulate GH hormone.hormone.

• Emerged as the first circulating hunger Emerged as the first circulating hunger hormone,increase food intake and fat hormone,increase food intake and fat massmass. .

• Discovery: Reported by Masayasu Discovery: Reported by Masayasu kojima (1999)kojima (1999)

• Root ghre;Root ghre; meaning to grow .meaning to grow .

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GHRELIN

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• Obestatine:Obestatine:• A 23-amino acid peptidA 23-amino acid peptid..• Found in late 2005 ,toFound in late 2005 ,to decreasedecrease appetite appetite..• Effects of obestatin on :Effects of obestatin on :1.1. GI motility.GI motility.2.2. Glucose homeostasis.Glucose homeostasis.3.3. Cell proliferations.Cell proliferations.4.4. Hormone secretion.Hormone secretion.5.5. Thirst,sleep,memory,anxiety,water intake.Thirst,sleep,memory,anxiety,water intake.6.6. Body weight ; energy expenditure.Body weight ; energy expenditure.7.7. Also induce early gene expression Also induce early gene expression

in:stomach,intestine,white adipose in:stomach,intestine,white adipose tissue,liver and kidneytissue,liver and kidney..

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• Singel session of circuit-resistanse Singel session of circuit-resistanse exercise at different intensities did exercise at different intensities did not change plasma obestatin not change plasma obestatin concentrations.concentrations.

• Only one study show:short(acute)and Only one study show:short(acute)and lung threadmill exercise have effect lung threadmill exercise have effect on on plasma plasma and and hypothalamushypothalamus ghrelin and obestatin levels.ghrelin and obestatin levels.

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• So;So;

We want explain on:We want explain on:

Effect of moderate-term threadmill Effect of moderate-term threadmill exerciseexercise

on fundus and intestine obestatin on fundus and intestine obestatin

concentraitions.concentraitions.

And see if existing this changing,what And see if existing this changing,what aboutabout

ATP concentrations in GI.ATP concentrations in GI.

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MATERIALS AND MATERIALS AND METHODMETHOD::1.1. Fourteen wistar male rats(14-16 weeks Fourteen wistar male rats(14-16 weeks

old)weighing 235-250g.old)weighing 235-250g.

2.2. Housed five per cage in with a volume Housed five per cage in with a volume 4L.4L.

3.3. 12:12 light-dark cycle.12:12 light-dark cycle.

4.4. Temperature :22±1.4 ˚CTemperature :22±1.4 ˚C

5.5. Humidity :55.6±4.0%Humidity :55.6±4.0%

6.6. Feed ad libitum and water.Feed ad libitum and water.

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• Rondomly asigned into 2 group:Rondomly asigned into 2 group:1.1. Control group(n=7)Control group(n=7)2.2. Training one(n=7)a moderate Training one(n=7)a moderate

running exercise program.running exercise program.• First familiarization of rats with First familiarization of rats with

apparatus for 4 days.apparatus for 4 days.• Exercise for 5 days/week for 6 weeksExercise for 5 days/week for 6 weeks• Fed but not exercise 48h prior to Fed but not exercise 48h prior to

sacrifice.sacrifice.• Food not water was removed from Food not water was removed from

cages 4h before experiment.cages 4h before experiment.

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•Tissue biopsies and blood Tissue biopsies and blood sample:sample:

• Anesthetized IP with ketamine and Anesthetized IP with ketamine and xylazine.xylazine.

• A part of fundus,upper small intestine A part of fundus,upper small intestine and liver were excised,clean divided and liver were excised,clean divided into 2 parts;washed in ice-cold into 2 parts;washed in ice-cold saline,frozen in liquid nitrogen.all parts saline,frozen in liquid nitrogen.all parts srored at -80˚C.srored at -80˚C.

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• Blood collected directly from heart in Blood collected directly from heart in test tubes containing test tubes containing EDTA,centrifugation,frozen and EDTA,centrifugation,frozen and stored -80˚C untill analysis.stored -80˚C untill analysis.

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• Fundus and intestine total Fundus and intestine total obestatin,ATP,liver obestatin,ATP,liver glycogen:glycogen:

Measured with EIA kit ,with minimum Measured with EIA kit ,with minimum detectable concentration 0.32 and 0.08detectable concentration 0.32 and 0.08ng/ml ,respectively for: fundus andng/ml ,respectively for: fundus andintestine total obestatin.intestine total obestatin.Fundus and intestine ATP was determined:Fundus and intestine ATP was determined:Bioaffina Gmbh ATP sensitiveBioaffina Gmbh ATP sensitivebioluminesence kit. bioluminesence kit. Liver glycogen determined by glycogen colometric kit.Liver glycogen determined by glycogen colometric kit.

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•Plasma glucose,growth Plasma glucose,growth hormone,insulin and cortisol hormone,insulin and cortisol concentrationconcentration::

• Plasma glucose determined by Plasma glucose determined by enzymatic colometric method.enzymatic colometric method.

• Plasma GH,insulin ,cortisol Plasma GH,insulin ,cortisol determined by ELISA method.determined by ELISA method.

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Result:Result:

• Significant diffrences not found in:Significant diffrences not found in:

Body weight.plasma glucose, cortisolBody weight.plasma glucose, cortisol

Consentrations.Consentrations.

Resting plasma total obestatin remaindResting plasma total obestatin remaind

Unchanged.Unchanged.

Total obestatin levels were significantlyTotal obestatin levels were significantly

decreased in traind rat fundus and decreased in traind rat fundus and intestineintestine..

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Fig. 1. Plasma, fundus, and intestine total obestatin concentrations in control and trained wild type male rats. Values are means ± SEM.

*Trained vs. control. Seven animals per group.

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• Fundus and intestine ATP concentration Fundus and intestine ATP concentration were unchanged.were unchanged.

• Higher glycogen concentration was Higher glycogen concentration was observed in trained rat liver.observed in trained rat liver.

• High concentration of GH level .High concentration of GH level .• **SO:negetive corrolations between both SO:negetive corrolations between both

fundus and intestine total obestatin fundus and intestine total obestatin concentrations and plasma GH levels.concentrations and plasma GH levels.

• No correlation between total obestatin No correlation between total obestatin concentration and any other variableconcentration and any other variable..

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Fig. 2. Plasma GH and liver glycogen concentrations in control and trained wild type male rats. *Trained vs. control. Values

are means ± SEM. Seven animals per group.

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DiscussionDiscussion

• The major findings of the present study The major findings of the present study were that fundus and intestine not plasma were that fundus and intestine not plasma obestatin concentrations were decreased obestatin concentrations were decreased and plasma GH level was elevated after the and plasma GH level was elevated after the treadmill exercise program.treadmill exercise program.

• Neither a single circuit-resistance exercise Neither a single circuit-resistance exercise at different intensities nor A short (acute) at different intensities nor A short (acute) and long-term treadmill exercise for 8 and long-term treadmill exercise for 8 weeks at 22 m/min did not change plasma weeks at 22 m/min did not change plasma obestatin levels in rat subjects .obestatin levels in rat subjects .

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• The mechanism(s) by which treadmill The mechanism(s) by which treadmill exercise reduces total obestatin exercise reduces total obestatin concentrations in rat fundus and intestine concentrations in rat fundus and intestine tissues is poorly understood.tissues is poorly understood.

• It has been suggested that plasma and It has been suggested that plasma and stomach ghrelin and obestatin levels are stomach ghrelin and obestatin levels are regulated by several hormones such as; regulated by several hormones such as; GH,insulin,somatostatin,glucagon.GH,insulin,somatostatin,glucagon.

• But;But; With consider to hormonal responses, only With consider to hormonal responses, only

plasma GH was significantly higher in plasma GH was significantly higher in trained rats .trained rats .

• A negative correlation has also been found A negative correlation has also been found between fundus and intestine total between fundus and intestine total concentrations and GH level Our results concentrations and GH level Our results are in agreement with the results were are in agreement with the results were previously reported by several studies.previously reported by several studies.

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• the growing information is exist about the growing information is exist about the effect of GH elevation upon plasma the effect of GH elevation upon plasma and stomach ghrelin suppression but and stomach ghrelin suppression but the information about the effect of the information about the effect of higher plasma GH on total obestatin higher plasma GH on total obestatin level is lacking.level is lacking.

• Food intake, glucose administration, Food intake, glucose administration, high-carbohydrate diet, and oral high-carbohydrate diet, and oral glucose tolerance test following a glucose tolerance test following a negative energy balance circumstances negative energy balance circumstances have been shown to decrease plasma have been shown to decrease plasma and stomach obestatin and ghrelin and stomach obestatin and ghrelin concentrations in human and animals concentrations in human and animals subjects.subjects.

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• Our data, however suggest that Our data, however suggest that 6 weeks treadmill exercise that 6 weeks treadmill exercise that increases hepatic glycogen level increases hepatic glycogen level which is accompanied with which is accompanied with reduction in total obestatin reduction in total obestatin concentrations in the fundus and concentrations in the fundus and intestine.intestine.

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• this is the first study this is the first study demonstrating that effect of demonstrating that effect of treadmill exercise upon fundus treadmill exercise upon fundus and intestine total obestatin and intestine total obestatin concentrations.concentrations.

• The present study is also the first The present study is also the first demonstrating that treadmill demonstrating that treadmill exercise reduces fundus and exercise reduces fundus and intestine total obestatin intestine total obestatin concentrations without a concentrations without a significant change in both fundus significant change in both fundus and intestine ATP levels.and intestine ATP levels.

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CONCLUSION:CONCLUSION:

• suggesting that treadmill suggesting that treadmill exercise training by enhancing exercise training by enhancing plasma GH and liver glycogen plasma GH and liver glycogen content may suppress fundus content may suppress fundus and intestine total obestatin and intestine total obestatin synthesis and their secretions.synthesis and their secretions. ((via a negative feedback action as proposed for via a negative feedback action as proposed for

ghrelin suppressionghrelin suppression.).)

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THANKS SO MUCH