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Article ; Online: Weight loss induces changes in adaptive thermogenesis in female and male physique athletes.

Isola, Ville / Hulmi, Juha J / Petäjä, Pirita / Helms, Eric R / Karppinen, Jari E / Ahtiainen, Juha P

Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme

2023 Volume 48, Issue 4, Page(s) 307–320

Abstract: Physique athletes lose substantial weight preparing for competitions, potentially altering systemic metabolism. We investigated sex differences in body composition, resting energy expenditure (REE), and appetite-regulating and thyroid hormone changes ... ...

Abstract	Physique athletes lose substantial weight preparing for competitions, potentially altering systemic metabolism. We investigated sex differences in body composition, resting energy expenditure (REE), and appetite-regulating and thyroid hormone changes during a competition preparation among drug-free physique athletes. The participants were female (10 competing (COMP) and 10 nondieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP were tested before they started their diet 23 weeks before competing (PRE), during their diet one week before competing (MID), and 23 weeks after competing (POST), whereas CTRL were tested at similar intervals but did not diet. Measurements included body composition by dual-energy X-ray absorptiometry, muscle size, and subcutaneous fat thickness (SFA) by ultrasound, REE by indirect calorimetry, circulating ghrelin, leptin T3, and T4 hormone analysis. Fat mass (FM) and SFA decreased in both sexes (
MeSH term(s)	Humans ; Female ; Male ; Leptin ; Basal Metabolism ; Weight Loss/physiology ; Energy Metabolism ; Body Composition ; Athletes ; Thermogenesis
Chemical Substances	Leptin
Language	English
Publishing date	2023-01-16
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2236708-1
ISSN	1715-5320 ; 1715-5312
ISSN (online)	1715-5320
ISSN	1715-5312
DOI	10.1139/apnm-2022-0372
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Article ; Online: Targeting the Activin Receptor Signaling to Counteract the Multi-Systemic Complications of Cancer and Its Treatments.

Hulmi, Juha J / Nissinen, Tuuli A / Penna, Fabio / Bonetto, Andrea

Cells

2021 Volume 10, Issue 3

Abstract: Muscle wasting, i.e., cachexia, frequently occurs in cancer and associates with poor prognosis and increased morbidity and mortality. Anticancer treatments have also been shown to contribute to sustainment or exacerbation of cachexia, thus affecting ... ...

Abstract	Muscle wasting, i.e., cachexia, frequently occurs in cancer and associates with poor prognosis and increased morbidity and mortality. Anticancer treatments have also been shown to contribute to sustainment or exacerbation of cachexia, thus affecting quality of life and overall survival in cancer patients. Pre-clinical studies have shown that blocking activin receptor type 2 (ACVR2) or its ligands and their downstream signaling can preserve muscle mass in rodents bearing experimental cancers, as well as in chemotherapy-treated animals. In tumor-bearing mice, the prevention of skeletal and respiratory muscle wasting was also associated with improved survival. However, the definitive proof that improved survival directly results from muscle preservation following blockade of ACVR2 signaling is still lacking, especially considering that concurrent beneficial effects in organs other than skeletal muscle have also been described in the presence of cancer or following chemotherapy treatments paired with counteraction of ACVR2 signaling. Hence, here, we aim to provide an up-to-date literature review on the multifaceted anti-cachectic effects of ACVR2 blockade in preclinical models of cancer, as well as in combination with anticancer treatments.
MeSH term(s)	Activin Receptors, Type II/metabolism ; Cachexia/etiology ; Cachexia/physiopathology ; Humans ; Neoplasms/complications ; Neoplasms/mortality ; Signal Transduction ; Survival Analysis
Chemical Substances	Activin Receptors, Type II (EC 2.7.11.30)
Language	English
Publishing date	2021-02-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10030516
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Article ; Online: Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1

Fachada, Vasco / Silvennoinen, Mika / Sahinaho, Ulla-Maria / Rahkila, Paavo / Kivelä, Riikka / Hulmi, Juha J / Kujala, Urho / Kainulainen, Heikki

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: 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 ... ...

Abstract	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-1α) 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-1α. 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.
MeSH term(s)	Humans ; Amino Acids, Branched-Chain/metabolism ; Exercise ; Lipids ; Muscle, Skeletal/metabolism ; Perilipin-2/metabolism ; Perilipins/metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Proteins/metabolism
Chemical Substances	Amino Acids, Branched-Chain ; Lipids ; Perilipin-2 ; Perilipins ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPARGC1A protein, human ; Proteins
Language	English
Publishing date	2023-02-21
Publishing country	Switzerland
Document type	Journal Article ; Twin Study
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24054282
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Article ; Online: Dietary Intake, Serum Hormone Concentrations, Amenorrhea and Bone Mineral Density of Physique Athletes and Active Gym Enthusiasts.

Mursu, Jaakko / Ristimäki, Maija / Malinen, Inga / Petäjä, Pirita / Isola, Ville / Ahtiainen, Juha P / Hulmi, Juha J

Nutrients

2023 Volume 15, Issue 2

Abstract: As the diet, hormones, amenorrhea, and bone mineral density (BMD) of physique athletes (PA) and gym enthusiasts (GE) are little-explored, we studied those in 69 females (50 PA, 19 GE) and 20 males (11 PA, 9 GE). Energy availability (EA, kcal·kgFFM−1·d−1 ... ...

Abstract	As the diet, hormones, amenorrhea, and bone mineral density (BMD) of physique athletes (PA) and gym enthusiasts (GE) are little-explored, we studied those in 69 females (50 PA, 19 GE) and 20 males (11 PA, 9 GE). Energy availability (EA, kcal·kgFFM−1·d−1 in DXA) in female and male PA was ~41.3 and ~37.2, and in GE ~39.4 and ~35.3, respectively. Low EA (LEA) was found in 10% and 26% of female PA and GE, respectively, and in 11% of male GE. In PA, daily protein intake (g/kg body mass) was ~2.9−3.0, whereas carbohydrate and fat intakes were ~3.6−4.3 and ~0.8−1.0, respectively. PA had higher protein and carbohydrate and lower fat intakes than GE (p < 0.05). Estradiol, testosterone, IGF-1, insulin, leptin, TSH, T4, T3, cortisol, or BMD did not differ between PA and GE. Serum IGF-1 and leptin were explained 6% and 7%, respectively, by EA. In non-users of hormonal contraceptives, amenorrhea was found only in PA (27%) and was associated with lower fat percentage, but not EA, BMD, or hormones. In conclusion, off-season dietary intakes, hormone levels, and BMD meet the recommendations in most of the PA and GE. Maintaining too-low body fat during the off-season may predispose to menstrual disturbances.
MeSH term(s)	Humans ; Male ; Female ; Amenorrhea/etiology ; Bone Density ; Leptin ; Insulin-Like Growth Factor I ; Athletes ; Running ; Eating ; Carbohydrates
Chemical Substances	Leptin ; Insulin-Like Growth Factor I (67763-96-6) ; Carbohydrates
Language	English
Publishing date	2023-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15020382
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Article ; Online: Interaction of the C2C12 myotube contractions and glucose availability on transcriptome and extracellular vesicle microRNAs.

Lautaoja-Kivipelto, Juulia H / Karvinen, Sira / Korhonen, Tia-Marje / O'Connell, Thomas M / Tiirola, Marja / Hulmi, Juha J / Pekkala, Satu

American journal of physiology. Cell physiology

2023 Volume 326, Issue 2, Page(s) C348–C361

Abstract: Exercise-like electrical pulse stimulation (EL-EPS) of myotubes mimics many key physiological changes induced by in vivo exercise. Besides enabling intracellular research, EL-EPS allows to study secreted factors, including muscle-specific microRNAs ( ... ...

Abstract	Exercise-like electrical pulse stimulation (EL-EPS) of myotubes mimics many key physiological changes induced by in vivo exercise. Besides enabling intracellular research, EL-EPS allows to study secreted factors, including muscle-specific microRNAs (myomiRs) carried in extracellular vesicles (EVs). These factors can participate in contraction-induced intercellular cross talk and may mediate the health benefits of exercise. However, the current knowledge of these responses, especially under variable nutritional conditions, is limited. We investigated the effects of EL-EPS on C2C12 myotube transcriptome in high- and low-glucose conditions by messenger RNA sequencing, while the expression of EV-carried miRNAs was analyzed by small RNA sequencing and RT-qPCR. We show that higher glucose availability augmented contraction-induced transcriptional changes and that the majority of the differentially expressed genes were upregulated. Furthermore, based on the pathway analyses, processes related to contractility and cytokine/inflammatory responses were upregulated. In addition, we report that EL-EPS increased packing of miR-1-3p into EVs independent of glucose availability. Together our findings suggest that in vitro EL-EPS is a usable tool not only to study contraction-induced intracellular mechanisms but also extracellular responses. The distinct transcriptional changes observed under variable nutritional conditions emphasize the importance of careful consideration of media composition in future exercise-mimicking studies.
MeSH term(s)	MicroRNAs/metabolism ; Muscle Contraction/physiology ; Glucose/pharmacology ; Glucose/metabolism ; Transcriptome ; Muscle Fibers, Skeletal/metabolism ; Cytokines/metabolism ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Electric Stimulation
Chemical Substances	MicroRNAs ; Glucose (IY9XDZ35W2) ; Cytokines
Language	English
Publishing date	2023-12-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00401.2023
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Article ; Online: Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling.

Lautaoja, Juulia H / Pekkala, Satu / Pasternack, Arja / Laitinen, Mika / Ritvos, Olli / Hulmi, Juha J

Biomolecules

2020 Volume 10, Issue 5

Abstract: Alongside in vivo models, a simpler and more mechanistic approach is required to study the effects of myostatin on skeletal muscle because myostatin is an important negative regulator of muscle size. In this study, myostatin was administered to murine ( ... ...

Abstract	Alongside in vivo models, a simpler and more mechanistic approach is required to study the effects of myostatin on skeletal muscle because myostatin is an important negative regulator of muscle size. In this study, myostatin was administered to murine (C2C12) and human (CHQ) myoblasts and myotubes. Canonical and noncanonical signaling downstream to myostatin, related ligands, and their receptor were analyzed. The effects of tumorkines were analyzed after coculture of C2C12 and colon cancer-C26 cells. The effects of myostatin on canonical and noncanonical signaling were strongly reduced in C2C12 cells after differentiation. This may be explained by increased follistatin, an endogenous blocker of myostatin and altered expression of activin receptor ligands. In contrast, CHQ cells were equally responsive to myostatin, and follistatin remained unaltered. Both myostatin administration and the coculture stimulated pathways associated with inflammation, especially in C2C12 cells. In conclusion, the effects of myostatin on intracellular signaling may be cell line- or organism-specific, and C2C12 myotubes seem to be a nonoptimal in vitro model for investigating the effects of myostatin on canonical and noncanonical signaling in skeletal muscle. This may be due to altered expression of activin receptor ligands and their regulators during muscle cell differentiation.
MeSH term(s)	Activins/metabolism ; Activins/pharmacology ; Animals ; Cell Differentiation ; Cell Line ; Cell Line, Tumor ; Culture Media, Conditioned/pharmacology ; Follistatin/metabolism ; Follistatin/pharmacology ; Humans ; Mice ; Muscle Fibers, Skeletal/cytology ; Muscle Fibers, Skeletal/drug effects ; Muscle Fibers, Skeletal/metabolism ; Myoblasts/cytology ; Myoblasts/drug effects ; Myoblasts/metabolism ; Myostatin/pharmacology ; Signal Transduction
Chemical Substances	Culture Media, Conditioned ; Follistatin ; Myostatin ; Activins (104625-48-1)
Language	English
Publishing date	2020-04-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom10050695
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Article ; Online: Sprint and Strength Training Modulates Autophagy and Proteostasis in Aging Sprinters.

Hentilä, Jaakko / Hulmi, Juha J / Laakkonen, Eija K / Ahtiainen, Juha P / Suominen, Harri / Korhonen, Marko T

Medicine and science in sports and exercise

2020 Volume 52, Issue 9, Page(s) 1948–1959

Abstract: Purpose: Exercise and aging may modulate muscle protein homeostasis and autophagy, but few studies examine highly trained middle-age or older individuals. This study elucidated the effects of a new long-term training stimulus on markers of muscle ... ...

Abstract	Purpose: Exercise and aging may modulate muscle protein homeostasis and autophagy, but few studies examine highly trained middle-age or older individuals. This study elucidated the effects of a new long-term training stimulus on markers of muscle autophagy and unfolded protein response (UPR) and on sprint running performance in masters sprinters. Methods: Thirty-two male competitive sprinters (age 40-76 yr) were randomly divided into experimental (EX) and control (CTRL) groups. The EX training program was a combination of heavy and explosive strength and sprint exercises aimed at improving sprint performance. Fifteen and thirteen participants completed the 20-wk intervention period in EX and CTRL, respectively. The latter were told to continue their routine exercises. Key protein markers were analyzed by Western blotting from vastus lateralis (VL) muscle biopsies. The muscle thickness of VL was analyzed by ultrasonography and sprint performance by a 60-m running test. Results: EX induced improvement in 60-m sprint performance when compared with controls (time-group, P = 0.003) without changes in VL muscle thickness. Content of lipidated microtubule-associated protein 1A/1B-light chain 3 (LC3-II) increased in EX (P = 0.022), suggesting increased autophagosome content. In addition, an autophagosome clearance marker sequestosome 1 (p62) decreased in EX (P = 0.006). Markers of UPR selectively modulated with decreases (e.g., ATF4, P = 0.003) and increases (e.g., EIF2α, P = 0.019) observed in EX. Conclusions: These findings suggest that a new intensive training stimulus that combines strength training with sprint training may increase muscle autophagosome content in a basal state without any evidence of impaired autophagosome clearance in masters sprinters. Simultaneously, the combined training may have a selective effect on the content of UPR signaling components.
MeSH term(s)	Adult ; Aged ; Aging/physiology ; Athletic Performance/physiology ; Autophagy ; Biomarkers/metabolism ; Endurance Training ; Glycolysis ; Humans ; Male ; Middle Aged ; Muscle Proteins/metabolism ; Muscle Proteins/physiology ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/physiology ; Proteostasis ; Resistance Training ; Running/physiology
Chemical Substances	Biomarkers ; Muscle Proteins
Language	English
Publishing date	2020-03-20
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	603994-7
ISSN	1530-0315 ; 0195-9131 ; 0025-7990
ISSN (online)	1530-0315
ISSN	0195-9131 ; 0025-7990
DOI	10.1249/MSS.0000000000002340
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Article ; Online: Serine synthesis pathway enzyme PHGDH is critical for muscle cell biomass, anabolic metabolism, and mTORC1 signaling.

Mäntyselkä, Sakari / Kolari, Kalle / Baumert, Philipp / Ylä-Outinen, Laura / Kuikka, Lauri / Lahtonen, Suvi / Permi, Perttu / Wackerhage, Henning / Kalenius, Elina / Kivelä, Riikka / Hulmi, Juha J

American journal of physiology. Endocrinology and metabolism

2023 Volume 326, Issue 1, Page(s) E73–E91

Abstract: Cells use glycolytic intermediates for anabolism, e.g., via the serine synthesis and pentose phosphate pathways. However, we still understand poorly how these metabolic pathways contribute to skeletal muscle cell biomass generation. The first aim of this ...

Abstract	Cells use glycolytic intermediates for anabolism, e.g., via the serine synthesis and pentose phosphate pathways. However, we still understand poorly how these metabolic pathways contribute to skeletal muscle cell biomass generation. The first aim of this study was therefore to identify enzymes that limit protein synthesis, myotube size, and proliferation in skeletal muscle cells. We inhibited key enzymes of glycolysis, the pentose phosphate pathway, and the serine synthesis pathway to evaluate their importance in C2C12 myotube protein synthesis. Based on the results of this first screen, we then focused on the serine synthesis pathway enzyme phosphoglycerate dehydrogenase (PHGDH). We used two different PHGDH inhibitors and mouse C2C12 and human primary muscle cells to study the importance and function of PHGDH. Both myoblasts and myotubes incorporated glucose-derived carbon into proteins, RNA, and lipids, and we showed that PHGDH is essential in these processes. PHGDH inhibition decreased protein synthesis, myotube size, and myoblast proliferation without cytotoxic effects. The decreased protein synthesis in response to PHGDH inhibition appears to occur mainly mechanistic target of rapamycin complex 1 (mTORC1)-dependently, as was evident from experiments with insulin-like growth factor 1 and rapamycin. Further metabolomics analyses revealed that PHGDH inhibition accelerated glycolysis and altered amino acid, nucleotide, and lipid metabolism. Finally, we found that supplementing an antioxidant and redox modulator,
MeSH term(s)	Animals ; Humans ; Mice ; Biomass ; Carbon/metabolism ; Cell Proliferation ; Glucose/metabolism ; Lipids ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Muscle Fibers, Skeletal/metabolism ; Phosphoglycerate Dehydrogenase/genetics ; Phosphoglycerate Dehydrogenase/metabolism ; RNA/metabolism ; Serine/metabolism
Chemical Substances	Carbon (7440-44-0) ; Glucose (IY9XDZ35W2) ; Lipids ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Phosphoglycerate Dehydrogenase (EC 1.1.1.95) ; RNA (63231-63-0) ; Serine (452VLY9402)
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00151.2023
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Article ; Online: Age But Not Menopausal Status Is Linked to Lower Resting Energy Expenditure.

Karppinen, Jari E / Wiklund, Petri / Ihalainen, Johanna K / Juppi, Hanna-Kaarina / Isola, Ville / Hyvärinen, Matti / Ahokas, Essi K / Kujala, Urho M / Laukkanen, Jari / Hulmi, Juha J / Ahtiainen, Juha P / Cheng, Sulin / Laakkonen, Eija K

The Journal of clinical endocrinology and metabolism

2023 Volume 108, Issue 11, Page(s) 2789–2797

Abstract: Context: It remains uncertain whether aging before late adulthood and menopause are associated with fat-free mass and fat mass-adjusted resting energy expenditure (REEadj).: Objectives: We investigated whether REEadj differs between middle-aged and ... ...

Abstract	Context: It remains uncertain whether aging before late adulthood and menopause are associated with fat-free mass and fat mass-adjusted resting energy expenditure (REEadj). Objectives: We investigated whether REEadj differs between middle-aged and younger women and between middle-aged women with different menopausal statuses. We repeated the age group comparison between middle-aged mothers and their daughters to partially control for genotype. We also explored whether serum estradiol and FSH concentrations explain REEadj in midlife. Methods: We divided 120 women, including 16 mother-daughter pairs, into age groups; group I (n = 26) consisted of participants aged 17 to 21, group II (n = 35) of those aged 22 to 38, and group III (n = 59) of those aged 41 to 58 years. The women in group III were further categorized as pre- or perimenopausal (n = 19), postmenopausal (n = 30), or postmenopausal hormone therapy users (n = 10). REE was assessed using indirect calorimetry, body composition using dual-energy X-ray absorptiometry, and hormones using immunoassays. Results: The REEadj of group I was 126 kcal/day [95% confidence interval (CI): 93-160] higher than that of group III, and the REEadj of group II was 88 kcal/day (95% CI: 49-127) higher. Furthermore, daughters had a 100 kcal/day (95% CI: 63-138 kcal/day) higher REEadj than their middle-aged mothers (all P < .001). In group III, REEadj was not lower in postmenopausal women and did not vary by sex hormone concentrations. Conclusions: We demonstrated that REEadj declines with age in women before late adulthood, also when controlling partially for genetic background, and that menopause may not contribute to this decline.
MeSH term(s)	Middle Aged ; Humans ; Female ; Adult ; Menopause ; Aging ; Energy Metabolism ; Body Composition ; Calorimetry, Indirect
Language	English
Publishing date	2023-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad321
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Article ; Online: Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation.

Lautaoja, Juulia H / M O'Connell, Thomas / Mäntyselkä, Sakari / Peräkylä, Juuli / Kainulainen, Heikki / Pekkala, Satu / Permi, Perttu / Hulmi, Juha J

American journal of physiology. Endocrinology and metabolism

2021 Volume 321, Issue 2, Page(s) E229–E245

Abstract: The application of exercise-like electrical pulse simulation (EL-EPS) has become a widely used exercise mimetic in vitro. EL-EPS produces similar physiological responses as in vivo exercise, while less is known about the detailed metabolic effects. ... ...

Abstract	The application of exercise-like electrical pulse simulation (EL-EPS) has become a widely used exercise mimetic in vitro. EL-EPS produces similar physiological responses as in vivo exercise, while less is known about the detailed metabolic effects. Routinely, the C2C12 myotubes are cultured in high-glucose medium (4.5 g/L), which may alter EL-EPS responses. In this study, we evaluate the metabolic effects of EL-EPS under the high- and low-glucose (1.0 g/L) conditions to understand how substrate availability affects the myotube response to EL-EPS. The C2C12 myotube, media, and cell-free media metabolites were analyzed using untargeted nuclear magnetic resonance (NMR)-based metabolomics. Furthermore, translational and metabolic changes and possible exerkine effects were analyzed. EL-EPS enhanced substrate utilization as well as production and secretion of lactate, acetate, 3-hydroxybutyrate, and branched-chain fatty acids (BCFAs). The increase in BCFAs correlated with branched-chain amino acids (BCAAs) and BCFAs were strongly decreased when myotubes were cultured without BCAAs suggesting the action of acyl-CoA thioesterases on BCAA catabolites. Notably, not all EL-EPS responses were augmented by high glucose because EL-EPS increased phosphorylated c-Jun N-terminal kinase and interleukin-6 secretion independent of glucose availability. Administration of acetate and EL-EPS conditioned media on HepG2 hepatocytes had no adverse effects on lipolysis or triacylglycerol content. Our results demonstrate that unlike in cell-free media, the C2C12 myotube and media metabolites were affected by EL-EPS, particularly under high-glucose condition suggesting that media composition should be considered in future EL-EPS studies. Furthermore, acetate and BCFAs were identified as putative exerkines warranting more research.
MeSH term(s)	Amino Acids, Branched-Chain/metabolism ; Animals ; Cells, Cultured ; Electric Stimulation ; Glucose/metabolism ; Mice ; Muscle Fibers, Skeletal/metabolism ; Physical Conditioning, Animal
Chemical Substances	Amino Acids, Branched-Chain ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00133.2021
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In stock of ZB MED Cologne/Königswinter

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More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito