Difference between revisions of "Distefano 2017 MiPschool Obergurgl"

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Effects of calorie restriction-induced weight loss and exercise on skeletal muscle mitochondrial energetics of older obese subjects.

Link: MITOEAGLE

Distefano G, Standley RA, Carnero EA, Cornnell HH, Coen PM, Goodpaster BH (2017)

Event: MiPschool Obergurgl 2017

Dysfunctional skeletal muscle mitochondria have been linked to aging, obesity and type 2 diabetes. Lifestyle interventions such as calorie restriction-induced weight loss (CRWL) and exercise are both known to improve muscle metabolism. However, the effects of these interventions on skeletal muscle mitochondria of older obese subjects are not clear. The purpose of this ongoing study is to investigate the effect of 6-month diet-induced weight loss intervention with or without the addition of exercise training on skeletal muscle mitochondrial energetics of older obese adults.

Thirty-six older (60-79yrs) adults with obesity (BMI=30-48kg/m²) have completed the study. Subjects were randomized to one of the following 6-month intervention: Health education (CON: n=14, 6M/8F), Calorie restriction-induced weight loss (CRWL: n=9, 4M/5F), or Weight-loss and exercise (WLEX: n=13, 5M/8F). CON subjects participated in biweekly health education sessions with no specific exercise/dietary advice. CRWL and WLEX participants had a goal of 10% weight-loss through calorie restriction. Subjects in the WLEX group completed a supervised exercise program. Mitochondrial energetics were determined in-vivo and ex-vivo before and after the 6-month intervention. In-vivo mitochondrial energetics was determined by ³¹P magnetic resonance spectroscopy. To complement the in-vivo measurement of mitochondrial energetics, a percutaneous biopsy of the vastus lateralis was collected. Saponin-permeabilized myofibers were used for assessment of mitochondrial respiratory capacity using high-resolution respirometry (Oxygraph-2k, OROBOROS INSTRUMENTS). Two SUIT protocols were employed, each performed in duplicate. Protocol 1 measured complex I+II supported LEAK respiration (CI&II_L), complex I+II supported maximal oxidative phosphorylation (OXPHOS) (CI&II_P), and maximal uncoupled respiration (CI&II_E). Protocol 2 measured FAO-supported LEAK respiration (FAOL) and FAO-supported OXPHOS (FAO_P). Titration of ADP (37.5-4000uM) was performed in both protocols to evaluate ADP sensitivity.

Our preliminary results showed no significant differences in the in-vivo ATP_max production between any of the groups (p>0.05). However, we found that while mitochondrial respiration was unchanged in the CON and CRWL groups after the 6-month intervention (p>0.05), subjects in the WLEX group presented an increased CI&II_L, CI&II_P, CI&II_E, FAO_L and FAO_P (p<0.05). Additionally, while Km was unchanged in the three groups after intervention, an increased Vmax in the exercise group after training was found. No differences in the intrinsic mitochondrial function, measured through flux control ratios, was observed between groups (p>0.05). The respirometry data collected for this study was also used to test the reproducibility of the method. We found that, on average, the coefficient of variation was 9.7%, the technical error of measurement was 12.8%, the concordance coefficient correlation was 0.670, and the bias correction factor was 0.969.

In summary, our results suggest that exercise is required to improve mitochondrial respiratory capacity in skeletal muscle of older obese human subjects undergoing calorie restriction-induced weight loss. The findings of this study provide significant insights on the influence of age and lifestyle interventions on skeletal muscle mitochondria, substantially contributing to the MITOEAGLE network.

• Bioblast editor: Kandolf G • O2k-Network Lab: US PA Pittsburgh Goodpaster BH

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Obesity

Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue

Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property. Pathway: F, NS HRR: Oxygraph-2k

Affiliations and support

Distefano G(1), Standley RA(1), Carnero EA(1), Cornnell HH(1), Coen PM(1,2), Goodpaster BH(1,2)

Translational Research Inst Metabolism and Diabetes, Florida Hospital;
Sanford Burnham Prebys Medical Discovery Inst Lake Nona, Orlando, Orlando, FL, USA.- [email protected]

This work was supported by the National Institutes of Health/National Institute on Aging (R01 AG021961 awarded to B.H.G.)

Instructions

All details: Abstracts

@@ Line 1: / Line 1: @@
 {{Abstract
 |title=[[File:MITOEAGLE-representation.jpg|left|60px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]]
+Effects of calorie restriction-induced weight loss and exercise on skeletal muscle mitochondrial energetics of older obese subjects.
 |info=[[MITOEAGLE]]
+|authors=Distefano G, Standley RA, Carnero EA, Cornnell HH, Coen PM, Goodpaster BH
 |year=2017
 |event=MiPschool Obergurgl 2017
 |abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]]
+Dysfunctional skeletal muscle mitochondria have been linked to aging, obesity and type 2 diabetes. Lifestyle interventions such as calorie restriction-induced weight loss (CRWL) and exercise are both known to improve muscle metabolism. However, the effects of these interventions on skeletal muscle mitochondria of older obese subjects are not clear. The purpose of this ongoing study is to investigate the effect of 6-month diet-induced weight loss intervention with or without the addition of exercise training on skeletal muscle mitochondrial energetics of older obese adults.
+Thirty-six older (60-79yrs) adults with obesity (BMI=30-48kg/m<sup>2</sup>) have completed the study. Subjects were randomized to one of the following 6-month intervention: Health education (CON: n=14, 6M/8F), Calorie restriction-induced weight loss (CRWL: n=9, 4M/5F), or Weight-loss and exercise (WLEX: n=13, 5M/8F). CON subjects participated in biweekly health education sessions with no specific exercise/dietary advice. CRWL and WLEX participants had a goal of 10% weight-loss through calorie restriction. Subjects in the WLEX group completed a supervised exercise program. Mitochondrial energetics were determined ''in-vivo'' and ''ex-vivo'' before and after the 6-month intervention. ''In-vivo'' mitochondrial energetics was determined by <sup>31</sup>P magnetic resonance spectroscopy. To complement the ''in-vivo'' measurement of mitochondrial energetics, a percutaneous biopsy of the vastus lateralis was collected. Saponin-permeabilized myofibers were used for assessment of mitochondrial respiratory capacity using high-resolution respirometry (Oxygraph-2k, OROBOROS INSTRUMENTS). Two SUIT protocols were employed, each performed in duplicate. Protocol 1 measured complex I+II supported LEAK respiration (CI&II<sub>''L''</sub>), complex I+II supported maximal oxidative phosphorylation (OXPHOS) (CI&II<sub>''P''</sub>), and maximal uncoupled respiration (CI&II<sub>''E''</sub>). Protocol 2 measured FAO-supported LEAK respiration (FAOL) and FAO-supported OXPHOS (FAO<sub>''P''</sub>). Titration of ADP (37.5-4000uM) was performed in both protocols to evaluate ADP sensitivity.
+Our preliminary results showed no significant differences in the ''in-vivo'' ATP<sub>max</sub> production between any of the groups (p>0.05). However, we found that while mitochondrial respiration was unchanged in the CON and CRWL groups after the 6-month intervention (p>0.05), subjects in the WLEX group presented an increased CI&II<sub>''L''</sub>, CI&II<sub>''P''</sub>, CI&II<sub>''E''</sub>, FAO<sub>''L''</sub> and FAO<sub>''P''</sub> (p<0.05). Additionally, while Km was unchanged in the three groups after intervention, an increased Vmax in the exercise group after training was found. No differences in the intrinsic mitochondrial function, measured through flux control ratios, was observed between groups (p>0.05). The respirometry data collected for this study was also used to test the reproducibility of the method. We found that, on average, the coefficient of variation was 9.7%, the technical error of measurement was 12.8%, the concordance coefficient correlation was 0.670, and the bias correction factor was 0.969.
+In summary, our results suggest that exercise is required to improve mitochondrial respiratory capacity in skeletal muscle of older obese human subjects undergoing calorie restriction-induced weight loss. The findings of this study provide significant insights on the influence of age and lifestyle interventions on skeletal muscle mitochondria, substantially contributing to the [[MITOEAGLE]] network.
+|editor=[[Kandolf G]]
+|mipnetlab=US PA Pittsburgh Goodpaster BH
+}}
+{{Labeling
+|area=Respiration, Exercise physiology;nutrition;life style
+|diseases=Obesity
+|organism=Human
+|tissues=Skeletal muscle
+|preparations=Permeabilized tissue
+|couplingstates=LEAK, OXPHOS, ETS
+|pathways=F, NS
+|instruments=Oxygraph-2k
 }}
-{{Labeling}}
+== Affiliations and support ==
-== Affiliations ==
+:::: Distefano G(1), Standley RA(1), Carnero EA(1), Cornnell HH(1), Coen PM(1,2), Goodpaster BH(1,2)
-:::: (1)
-::::#
+::::#Translational Research Inst Metabolism and Diabetes, Florida Hospital;
+::::#Sanford Burnham Prebys Medical Discovery Inst Lake Nona, Orlando, Orlando, FL, USA.- [email protected]
-== Figure 1 ==
+:::::This work was supported by the National Institutes of Health/National Institute on Aging (R01 AG021961 awarded to B.H.G.)