Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1<i>α</i>

Cellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and th...

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Main Authors: Vasco Fachada, Mika Silvennoinen, Ulla-Maria Sahinaho, Paavo Rahkila, Riikka Kivelä, Juha J. Hulmi, Urho Kujala, Heikki Kainulainen
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/5/4282
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author Vasco Fachada
Mika Silvennoinen
Ulla-Maria Sahinaho
Paavo Rahkila
Riikka Kivelä
Juha J. Hulmi
Urho Kujala
Heikki Kainulainen
author_facet Vasco Fachada
Mika Silvennoinen
Ulla-Maria Sahinaho
Paavo Rahkila
Riikka Kivelä
Juha J. Hulmi
Urho Kujala
Heikki Kainulainen
author_sort Vasco Fachada
collection DOAJ
description Cellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and their related key proteins in response to physical activity and BCAA deprivation. By means of confocal microscopy, we examined IMCL and the lipid droplet coating proteins PLIN2 and PLIN5 in human twin pairs discordant for physical activity. Additionally, in order to study IMCLs, PLINs and their association to peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula>) in cytosolic and nuclear pools, we mimicked exercise-induced contractions in C2C12 myotubes by electrical pulse stimulation (EPS), with or without BCAA deprivation. The life-long physically active twins displayed an increased IMCL signal in type I fibers when compared to their inactive twin pair. Moreover, the inactive twins showed a decreased association between PLIN2 and IMCL. Similarly, in the C2C12 cell line, PLIN2 dissociated from IMCL when myotubes were deprived of BCAA, especially when contracting. In addition, in myotubes, EPS led to an increase in nuclear PLIN5 signal and its associations with IMCL and PGC-1<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula>. This study demonstrates how physical activity and BCAA availability affects IMCL and their associated proteins, providing further and novel evidence for the link between the BCAA, energy and lipid metabolisms.
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spelling doaj.art-6e42b1a9192845d3b53de8f2055c29d32023-11-17T07:46:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245428210.3390/ijms24054282Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1<i>α</i>Vasco Fachada0Mika Silvennoinen1Ulla-Maria Sahinaho2Paavo Rahkila3Riikka Kivelä4Juha J. Hulmi5Urho Kujala6Heikki Kainulainen7Faculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, FI-40014 Jyväskylä, FinlandFaculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, FI-40014 Jyväskylä, FinlandFaculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, FI-40014 Jyväskylä, FinlandFaculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, FI-40014 Jyväskylä, FinlandFaculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, FI-40014 Jyväskylä, FinlandFaculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, FI-40014 Jyväskylä, FinlandFaculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, FI-40014 Jyväskylä, FinlandFaculty of Sport and Health Sciences, NeuroMuscular Research Center, University of Jyväskylä, FI-40014 Jyväskylä, FinlandCellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and their related key proteins in response to physical activity and BCAA deprivation. By means of confocal microscopy, we examined IMCL and the lipid droplet coating proteins PLIN2 and PLIN5 in human twin pairs discordant for physical activity. Additionally, in order to study IMCLs, PLINs and their association to peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula>) in cytosolic and nuclear pools, we mimicked exercise-induced contractions in C2C12 myotubes by electrical pulse stimulation (EPS), with or without BCAA deprivation. The life-long physically active twins displayed an increased IMCL signal in type I fibers when compared to their inactive twin pair. Moreover, the inactive twins showed a decreased association between PLIN2 and IMCL. Similarly, in the C2C12 cell line, PLIN2 dissociated from IMCL when myotubes were deprived of BCAA, especially when contracting. In addition, in myotubes, EPS led to an increase in nuclear PLIN5 signal and its associations with IMCL and PGC-1<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula>. This study demonstrates how physical activity and BCAA availability affects IMCL and their associated proteins, providing further and novel evidence for the link between the BCAA, energy and lipid metabolisms.https://www.mdpi.com/1422-0067/24/5/4282lipid dropletsPLIN2PLIN5skeletal musclephysical activityC2C12
spellingShingle Vasco Fachada
Mika Silvennoinen
Ulla-Maria Sahinaho
Paavo Rahkila
Riikka Kivelä
Juha J. Hulmi
Urho Kujala
Heikki Kainulainen
Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1<i>α</i>
International Journal of Molecular Sciences
lipid droplets
PLIN2
PLIN5
skeletal muscle
physical activity
C2C12
title Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1<i>α</i>
title_full Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1<i>α</i>
title_fullStr Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1<i>α</i>
title_full_unstemmed Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1<i>α</i>
title_short Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1<i>α</i>
title_sort effects of long term physical activity and bcaa availability on the subcellular associations between intramyocellular lipids perilipins and pgc 1 i α i
topic lipid droplets
PLIN2
PLIN5
skeletal muscle
physical activity
C2C12
url https://www.mdpi.com/1422-0067/24/5/4282
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