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11 results on '"Lautaoja, Juulia H."'

2. Branched-Chain Amino Acid Deprivation Decreases Lipid Oxidation and Lipogenesis in C2C12 Myotubes

Author

Karvinen, Sira, Fachada, Vasco, Sahinaho, Ulla-Maria, Pekkala, Satu, Lautaoja, Juulia H., Mäntyselkä, Sakari, Permi, Perttu, Hulmi, Juha J., Silvennoinen, Mika, Kainulainen, Heikki, Institute of Biotechnology, and Helsinki Institute of Life Science HiLIFE

Subjects
metabolic health, EXERCISE, aminohapot, METABOLISM, DEHYDROGENASE COMPLEX, SUPPLEMENTATION, rasva-aineenvaihdunta, in vitro exercise, ALPHA, ACTIVATION, MICE, aineenvaihduntahäiriöt, CONTRACTION, electrical pulse stimulation, SKELETAL-MUSCLE, 1182 Biochemistry, cell and molecular biology, lipids (amino acids, peptides, and proteins), skeletal muscle, aikuistyypin diabetes, OBESE, lihassolut, protein supplementation, nuclear magnetic resonance spectroscopy
Abstract

Impaired lipid metabolism is a common risk factor underlying several metabolic diseases such as metabolic syndrome and type 2 diabetes. Branched-chain amino acids (BCAAs) that include valine, leucine and isoleucine have been proven to share a role in lipid metabolism and hence in maintaining metabolic health. We have previously introduced a hypothesis suggesting that BCAA degradation mechanistically connects to lipid oxidation and storage in skeletal muscle. To test our hypothesis, the present study examined the effects of BCAA deprivation and supplementation on lipid oxidation, lipogenesis and lipid droplet characteristics in murine C2C12 myotubes. In addition, the role of myotube contractions on cell metabolism was studied by utilizing in vitro skeletal-muscle-specific exercise-like electrical pulse stimulation (EPS). Our results showed that the deprivation of BCAAs decreased both lipid oxidation and lipogenesis in C2C12 myotubes. BCAA deprivation further diminished the number of lipid droplets in the EPS-treated myotubes. EPS decreased lipid oxidation especially when combined with high BCAA supplementation. Similar to BCAA deprivation, high BCAA supplementation also decreased lipid oxidation. The present results highlight the role of an adequate level of BCAAs in healthy lipid metabolism.

Published
2022

5. Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling

Author

Lautaoja, Juulia H., Pekkala, Satu, Pasternack, Arja, Laitinen, Mika, Ritvos, Olli, Hulmi, Juha J., Medicum, Department of Physiology, Faculty of Medicine, University of Helsinki, HUS Internal Medicine and Rehabilitation, Department of Medicine, Helsinki University Hospital Area, and Growth factor physiology

Subjects
Muscle Fibers, Skeletal, lcsh:QR1-502, lihakset, lcsh:Microbiology, Article, TGF-BETA SUPERFAMILY, Cell Line, Myoblasts, Mice, tumorkine, Cell Line, Tumor, follistatin, Animals, Humans, CANCER CACHEXIA, skeletal muscle, MUSCLE ATROPHY, lihassolut, Smad, soluviestintä, RECEPTOR, Cell Differentiation, IN-VITRO, Myostatin, musculoskeletal system, MAPK, Activins, LEUKEMIA INHIBITORY FACTOR, ACTIVIN-A, inflammation, Culture Media, Conditioned, CELLS, PROTEIN-SYNTHESIS, myotube, GROWTH, 1182 Biochemistry, cell and molecular biology, proteiinit, 3111 Biomedicine, coculture, Signal Transduction
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.

Published
2020

11. Prevention of chemotherapy‐induced cachexia by ACVR2B ligand blocking has different effects on heart and skeletal muscle.

Author

Hulmi, Juha J., Nissinen, Tuuli A., Räsänen, Markus, Degerman, Joni, Lautaoja, Juulia H., Hemanthakumar, Karthik Amudhala, Backman, Janne T., Ritvos, Olli, Silvennoinen, Mika, and Kivelä, Riikka

Subjects
CACHEXIA, CHEMOTHERAPY complications, CANCER chemotherapy, QUALITY of life, TRANSFERRIN, ANTINEOPLASTIC agents, ACTIVIN receptors
Abstract

Abstract: Background: Toxicity of chemotherapy on skeletal muscles and the heart may significantly contribute to cancer cachexia, mortality, and decreased quality of life. Doxorubicin (DOX) is an effective cytostatic agent, which unfortunately has toxic effects on many healthy tissues. Blocking of activin receptor type IIB (ACVR2B) ligands is an often used strategy to prevent skeletal muscle loss, but its effects on the heart are relatively unknown. Methods: The effects of DOX treatment with or without pre‐treatment with soluble ACVR2B‐Fc (sACVR2B‐Fc) were investigated. The mice were randomly assigned into one of the three groups: (1) vehicle (PBS)‐treated controls, (2) DOX‐treated mice (DOX), and (3) DOX‐treated mice administered with sACVR2B‐Fc during the experiment (DOX + sACVR2B‐Fc). DOX was administered with a cumulative dose of 24 mg/kg during 2 weeks to investigate cachexia outcome in the heart and skeletal muscle. To understand similarities and differences between skeletal and cardiac muscles in their responses to chemotherapy, the tissues were collected 20 h after a single DOX (15 mg/kg) injection and analysed with genome‐wide transcriptomics and mRNA and protein analyses. The combination group was pre‐treated with sACVR2B‐Fc 48 h before DOX administration. Major findings were also studied in mice receiving only sACVR2B‐Fc. Results: The DOX treatment induced similar (~10%) wasting in skeletal muscle and the heart. However, transcriptional changes in response to DOX were much greater in skeletal muscle. Pathway analysis and unbiased transcription factor analysis showed that p53‐p21‐REDD1 is the main common pathway activated by DOX in both skeletal and cardiac muscles. These changes were attenuated by blocking ACVR2B ligands especially in skeletal muscle. Tceal7 (3‐fold to 5‐fold increase), transferrin receptor (1.5‐fold increase), and Ccl21 (0.6‐fold to 0.9‐fold decrease) were identified as novel genes responsive to blocking ACVR2B ligands. Overall, at the transcriptome level, ACVR2B ligand blocking had only minor influence in the heart while it had marked effects in skeletal muscle. The same was also true for the effects on tissue wasting. This may be explained in part by about 18‐fold higher gene expression of myostatin in skeletal muscle compared with the heart. Conclusions: Cardiac and skeletal muscles display similar atrophy after DOX treatment, but the mechanisms for this may differ between the tissues. The present results suggest that p53‐p21‐REDD1 signalling is the main common DOX‐activated pathway in these tissues and that blocking activin receptor ligands attenuates this response, especially in skeletal muscle supporting the overall stronger effects of this treatment in skeletal muscles. [ABSTRACT FROM AUTHOR]

Published
2018
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