Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Supplemental material
  • Version history
  • Article usage
  • Citations to this article
Advertisement

ResearchIn-Press PreviewMetabolismTherapeutics Open Access | 10.1172/jci.insight.150461

A compound directed against S6K1 hampers fat mass expansion and mitigates diet-induced hepatosteatosis

Aina Lluch,1 Sonia R. Veiga,2 Jèssica Latorre,1 José M. Moreno-Navarrete,3 Núria Bonifaci,4 Van Dien Nguyen,5 You Zhou,6 Marcus Horing,7 Gerhard Liebisch,8 Vesa M. Olkkonen,9 David Llobet-Navas,10 George Thomas,11 Ruth Rodriguez-Barrueco,12 José M. Fernández-Real,13 Sara C. Kozma,11 and Francisco J. Ortega1

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Lluch, A. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Veiga, S. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Latorre, J. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Moreno-Navarrete, J. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Bonifaci, N. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Nguyen, V. in: JCI | PubMed | Google Scholar

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Zhou, Y. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Horing, M. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Liebisch, G. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Olkkonen, V. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Llobet-Navas, D. in: JCI | PubMed | Google Scholar |

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Thomas, G. in: JCI | PubMed | Google Scholar

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Rodriguez-Barrueco, R. in: JCI | PubMed | Google Scholar

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Fernández-Real, J. in: JCI | PubMed | Google Scholar

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Kozma, S. in: JCI | PubMed | Google Scholar

1Department of Diabetes, Endocrinology, and Nutrition (UDEN), Girona Biomedical Research Institute (IDIBGI), Girona, Spain

2Department of Aging & Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

3Girona Biomedical Research Institute (IDIBGI), Girona, Spain

4Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

5Division of Infection and Immunity, Cardiff University School of Medicine, Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

6Systems Immunity Research Institute, Cardiff University, Cardiff, United Kingdom

7Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

8Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

9Biomedicum, Minerva Foundation Institute for Medical Research, Helsinki, Finland

10Institute of Genetic Medicine, Newcastle University, Newastle, United Kingdom

11Laboratory of Cancer Metabolism, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain

12School of Medicine, University of Barcelona (UB), Barcelona, Spain

13Department of Endocrinology, Girona Biomedical Research Institute (IDIBGI), Girona, Spain

Find articles by Ortega, F. in: JCI | PubMed | Google Scholar |

Published June 23, 2022 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.150461.
Copyright © 2022, Lluch et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 23, 2022 - Version history
View PDF
Abstract

The ribosomal protein S6 kinase 1 (S6K1) is a relevant effector downstream the mammalian target of rapamycin complex 1 (mTORC1), best known for its role in the control of lipid homeostasis. Consistent with this, mice lacking the S6k1 gene have a defect in their ability to induce the commitment of fat precursor cells to the adipogenic lineage, which contributes to a significant reduction of fat mass. Here, we assess the therapeutic blockage of S6K1 in diet-induced obese mice challenged with LY2584702 tosylate, a specific oral S6K1 inhibitor initially developed for the treatment of solid tumours. We show that diminished S6K1 activity hampers fat mass expansion and ameliorates dyslipidaemia and hepatic steatosis, while modifying transcriptome-wide gene expression programs relevant for adipose and liver function. Accordingly, impaired mTORC1 signalling in fat (decreased) and liver (increased) co-segregated with defective epithelial-mesenchymal transition, being prominent the decreased expression of Cd36 (coding for a fatty acid translocase) and Lgals1 (Galectin 1) in both tissues. All these factors combined align with reduced adipocyte size and improved lipidomic signatures in the liver, while hepatic steatosis and hypertriglyceridemia were improved in treatments lasting either 3 months or 6 weeks.

Graphical Abstract
graphical abstract
Supplemental material

View Supplemental Figures S1-S8

View

Version history
  • Version 1 (June 23, 2022): In-Press Preview

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Supplemental material
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts