ResearchIn-Press PreviewMetabolismTherapeutics
Open Access | 10.1172/jci.insight.150461
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
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Lluch, A.
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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
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Veiga, S.
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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
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Latorre, J.
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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
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Moreno-Navarrete, J.
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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
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Bonifaci, N.
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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
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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
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Zhou, Y.
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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
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Horing, M.
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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
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Liebisch, G.
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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
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Olkkonen, V.
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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
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Llobet-Navas, D.
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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
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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
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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
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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
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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
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Ortega, F.
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Published June 23, 2022 - More info
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.