Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity

Andrea Benova; Michaela Ferencakova; Kristina Bardova; Jiri Funda; Jan Prochazka; Frantisek Spoutil; Tomas Cajka; Martina Dzubanova; Tim Balcaen; Greet Kerckhofs; Wouter Willekens; G. Harry van Lenthe; Arzuv Charyyeva; Glenda Alquicer; Alena Pecinova; Tomas Mracek; Olga Horakova; Roman Coupeau; Morten Svarer Hansen; Martin Rossmeisl; Jan Kopecky; Michaela Tencerova

doi:10.1038/s42003-023-05407-8

Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity

Andrea Benova
, Michaela Ferencakova
, Kristina Bardova
, Jiri Funda
, Jan Prochazka
, Frantisek Spoutil
, Tomas Cajka
, Martina Dzubanova
, Tim Balcaen
, Greet Kerckhofs
, Wouter Willekens
, G. Harry van Lenthe
, Arzuv Charyyeva
, Glenda Alquicer
, Alena Pecinova
, Tomas Mracek
, Olga Horakova
, Roman Coupeau
, Morten Svarer Hansen
, Martin Rossmeisl

Jan Kopecky, Michaela Tencerova^*

^*Corresponding author for this work

The Czech Academy of Sciences
Charles University
Catholic University of Louvain
University of Leuven

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

Original language	English
Article number	1043
Journal	Communications Biology
Volume	6
Number of pages	17
ISSN	2399-3642
DOIs	https://doi.org/10.1038/s42003-023-05407-8
Publication status	Published - 14. Oct 2023

Funding

We would like to thank the Histology Core facility at CCP Biocev for their excellent work in the preparation of bone samples. We thank Kimberly Crevits at FIBEr, KU Leuven, for performing the three-point bending tests. We would like to thank Dr. Ondrej Kuda from IPHYS, CAS for his scientific input in omega-3 PUFA experiments. We are grateful for the help writing the MATLAB script for automatic histogram windowing and relative gray value normalization of CECT images to Arne Maes from KU Leuven. We are thankful for omega-3 PUFA concentrate provided by Epax Norway AS (Ålesund, Norway). The authors would like to acknowledge the Metabolomics Core Facility at the Institute of Physiology of the Czech Academy of Sciences for global metabolomic and lipidomic profiling. This work was supported by START UP Research program by the Institute of Physiology of the Czech Academy of Sciences and the Czech Science Foundation GACR 20-03586S (M.T.), GACR 19-02411S (J.K.), EFSD/NovoNordisk foundation Future leaders award (NNF20SA0066174), National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU, Grant Agency of Charles University GAUK 339821 (A.B.), FRIA grant 40008717 (T.B.) and FWO G088218N (G.K. and T.B.). We would like to thank the Histology Core facility at CCP Biocev for their excellent work in the preparation of bone samples. We thank Kimberly Crevits at FIBEr, KU Leuven, for performing the three-point bending tests. We would like to thank Dr. Ondrej Kuda from IPHYS, CAS for his scientific input in omega-3 PUFA experiments. We are grateful for the help writing the MATLAB script for automatic histogram windowing and relative gray value normalization of CECT images to Arne Maes from KU Leuven. We are thankful for omega-3 PUFA concentrate provided by Epax Norway AS (Ålesund, Norway). The authors would like to acknowledge the Metabolomics Core Facility at the Institute of Physiology of the Czech Academy of Sciences for global metabolomic and lipidomic profiling. This work was supported by START UP Research program by the Institute of Physiology of the Czech Academy of Sciences and the Czech Science Foundation GACR 20-03586S (M.T.), GACR 19-02411S (J.K.), EFSD/NovoNordisk foundation Future leaders award (NNF20SA0066174), National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU, Grant Agency of Charles University GAUK 339821 (A.B.), FRIA grant 40008717 (T.B.) and FWO G088218N (G.K. and T.B.).

Keywords

Adiposity
Animals
Bone Marrow/metabolism
Bone and Bones/metabolism
Disease Models, Animal
Fatty Acids, Omega-3/pharmacology
Humans
Mice
Obesity/complications

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Benova, A., Ferencakova, M., Bardova, K., Funda, J., Prochazka, J., Spoutil, F., Cajka, T., Dzubanova, M., Balcaen, T., Kerckhofs, G., Willekens, W., van Lenthe, G. H., Charyyeva, A., Alquicer, G., Pecinova, A., Mracek, T., Horakova, O., Coupeau, R., Hansen, M. S., ... Tencerova, M. (2023). Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity. Communications Biology, 6, Article 1043. https://doi.org/10.1038/s42003-023-05407-8

@article{0f1b5153ca7c46609b5f4c19ebe860e2,

title = "Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity",

abstract = "Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.",

keywords = "Adiposity, Animals, Bone Marrow/metabolism, Bone and Bones/metabolism, Disease Models, Animal, Fatty Acids, Omega-3/pharmacology, Humans, Mice, Obesity/complications",

author = "Andrea Benova and Michaela Ferencakova and Kristina Bardova and Jiri Funda and Jan Prochazka and Frantisek Spoutil and Tomas Cajka and Martina Dzubanova and Tim Balcaen and Greet Kerckhofs and Wouter Willekens and \{van Lenthe\}, \{G. Harry\} and Arzuv Charyyeva and Glenda Alquicer and Alena Pecinova and Tomas Mracek and Olga Horakova and Roman Coupeau and Hansen, \{Morten Svarer\} and Martin Rossmeisl and Jan Kopecky and Michaela Tencerova",

note = "Funding Information: We would like to thank the Histology Core facility at CCP Biocev for their excellent work in the preparation of bone samples. We thank Kimberly Crevits at FIBEr, KU Leuven, for performing the three-point bending tests. We would like to thank Dr. Ondrej Kuda from IPHYS, CAS for his scientific input in omega-3 PUFA experiments. We are grateful for the help writing the MATLAB script for automatic histogram windowing and relative gray value normalization of CECT images to Arne Maes from KU Leuven. We are thankful for omega-3 PUFA concentrate provided by Epax Norway AS ({\AA}lesund, Norway). The authors would like to acknowledge the Metabolomics Core Facility at the Institute of Physiology of the Czech Academy of Sciences for global metabolomic and lipidomic profiling. This work was supported by START UP Research program by the Institute of Physiology of the Czech Academy of Sciences and the Czech Science Foundation GACR 20-03586S (M.T.), GACR 19-02411S (J.K.), EFSD/NovoNordisk foundation Future leaders award (NNF20SA0066174), National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID Project No. LX22NPO5104){\textemdash}Funded by the European Union{\textemdash}Next Generation EU, Grant Agency of Charles University GAUK 339821 (A.B.), FRIA grant 40008717 (T.B.) and FWO G088218N (G.K. and T.B.). Funding Information: We would like to thank the Histology Core facility at CCP Biocev for their excellent work in the preparation of bone samples. We thank Kimberly Crevits at FIBEr, KU Leuven, for performing the three-point bending tests. We would like to thank Dr. Ondrej Kuda from IPHYS, CAS for his scientific input in omega-3 PUFA experiments. We are grateful for the help writing the MATLAB script for automatic histogram windowing and relative gray value normalization of CECT images to Arne Maes from KU Leuven. We are thankful for omega-3 PUFA concentrate provided by Epax Norway AS ({\AA}lesund, Norway). The authors would like to acknowledge the Metabolomics Core Facility at the Institute of Physiology of the Czech Academy of Sciences for global metabolomic and lipidomic profiling. This work was supported by START UP Research program by the Institute of Physiology of the Czech Academy of Sciences and the Czech Science Foundation GACR 20-03586S (M.T.), GACR 19-02411S (J.K.), EFSD/NovoNordisk foundation Future leaders award (NNF20SA0066174), National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID Project No. LX22NPO5104){\textemdash}Funded by the European Union{\textemdash}Next Generation EU, Grant Agency of Charles University GAUK 339821 (A.B.), FRIA grant 40008717 (T.B.) and FWO G088218N (G.K. and T.B.). ",

year = "2023",

month = oct,

day = "14",

doi = "10.1038/s42003-023-05407-8",

language = "English",

volume = "6",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Nature Publishing Group",

}

Benova, A, Ferencakova, M, Bardova, K, Funda, J, Prochazka, J, Spoutil, F, Cajka, T, Dzubanova, M, Balcaen, T, Kerckhofs, G, Willekens, W, van Lenthe, GH, Charyyeva, A, Alquicer, G, Pecinova, A, Mracek, T, Horakova, O, Coupeau, R, Hansen, MS, Rossmeisl, M, Kopecky, J & Tencerova, M 2023, 'Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity', Communications Biology, vol. 6, 1043. https://doi.org/10.1038/s42003-023-05407-8

TY - JOUR

T1 - Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity

AU - Benova, Andrea

AU - Ferencakova, Michaela

AU - Bardova, Kristina

AU - Funda, Jiri

AU - Prochazka, Jan

AU - Spoutil, Frantisek

AU - Cajka, Tomas

AU - Dzubanova, Martina

AU - Balcaen, Tim

AU - Kerckhofs, Greet

AU - Willekens, Wouter

AU - van Lenthe, G. Harry

AU - Charyyeva, Arzuv

AU - Alquicer, Glenda

AU - Pecinova, Alena

AU - Mracek, Tomas

AU - Horakova, Olga

AU - Coupeau, Roman

AU - Hansen, Morten Svarer

AU - Rossmeisl, Martin

AU - Kopecky, Jan

AU - Tencerova, Michaela

N1 - Funding Information: We would like to thank the Histology Core facility at CCP Biocev for their excellent work in the preparation of bone samples. We thank Kimberly Crevits at FIBEr, KU Leuven, for performing the three-point bending tests. We would like to thank Dr. Ondrej Kuda from IPHYS, CAS for his scientific input in omega-3 PUFA experiments. We are grateful for the help writing the MATLAB script for automatic histogram windowing and relative gray value normalization of CECT images to Arne Maes from KU Leuven. We are thankful for omega-3 PUFA concentrate provided by Epax Norway AS (Ålesund, Norway). The authors would like to acknowledge the Metabolomics Core Facility at the Institute of Physiology of the Czech Academy of Sciences for global metabolomic and lipidomic profiling. This work was supported by START UP Research program by the Institute of Physiology of the Czech Academy of Sciences and the Czech Science Foundation GACR 20-03586S (M.T.), GACR 19-02411S (J.K.), EFSD/NovoNordisk foundation Future leaders award (NNF20SA0066174), National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU, Grant Agency of Charles University GAUK 339821 (A.B.), FRIA grant 40008717 (T.B.) and FWO G088218N (G.K. and T.B.). Funding Information: We would like to thank the Histology Core facility at CCP Biocev for their excellent work in the preparation of bone samples. We thank Kimberly Crevits at FIBEr, KU Leuven, for performing the three-point bending tests. We would like to thank Dr. Ondrej Kuda from IPHYS, CAS for his scientific input in omega-3 PUFA experiments. We are grateful for the help writing the MATLAB script for automatic histogram windowing and relative gray value normalization of CECT images to Arne Maes from KU Leuven. We are thankful for omega-3 PUFA concentrate provided by Epax Norway AS (Ålesund, Norway). The authors would like to acknowledge the Metabolomics Core Facility at the Institute of Physiology of the Czech Academy of Sciences for global metabolomic and lipidomic profiling. This work was supported by START UP Research program by the Institute of Physiology of the Czech Academy of Sciences and the Czech Science Foundation GACR 20-03586S (M.T.), GACR 19-02411S (J.K.), EFSD/NovoNordisk foundation Future leaders award (NNF20SA0066174), National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU, Grant Agency of Charles University GAUK 339821 (A.B.), FRIA grant 40008717 (T.B.) and FWO G088218N (G.K. and T.B.).

PY - 2023/10/14

Y1 - 2023/10/14

N2 - Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

AB - Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

KW - Adiposity

KW - Animals

KW - Bone Marrow/metabolism

KW - Bone and Bones/metabolism

KW - Disease Models, Animal

KW - Fatty Acids, Omega-3/pharmacology

KW - Humans

KW - Mice

KW - Obesity/complications

U2 - 10.1038/s42003-023-05407-8

DO - 10.1038/s42003-023-05407-8

M3 - Journal article

C2 - 37833362

AN - SCOPUS:85174275716

SN - 2399-3642

VL - 6

JO - Communications Biology

JF - Communications Biology

M1 - 1043

ER -

Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity

Abstract

Funding

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