Author
Listed:
- Anastasia Georgiadi
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Valeria Lopez-Salazar
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Rabih El- Merahbi
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Rhoda Anane Karikari
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Xiaochuan Ma
(Karolinska Institute)
- André Mourão
(German Research Center for Environmental Health)
- Katarina Klepac
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Lea Bühler
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Ana Jimena Alfaro
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Isabell Kaczmarek
(University of Leipzig)
- Adam Linford
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Madeleen Bosma
(Karolinska Institute)
- Olga Shilkova
(Karolinska Institute)
- Olli Ritvos
(University of Helsinki)
- Nobuhiro Nakamura
(Tokyo Institute of Technology)
- Shigehisa Hirose
(Tokyo Institute of Technology)
- Maximilian Lassi
(German Center for Diabetes Research (DZD)
German Research Center for Environmental Health)
- Raffaele Teperino
(German Center for Diabetes Research (DZD)
German Research Center for Environmental Health)
- Juliano Machado
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Marcel Scheideler
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
- Arne Dietrich
(University of Leipzig)
- Arie Geerlof
(German Research Center for Environmental Health)
- Annette Feuchtinger
(German Research Center for Environmental Health)
- Andreas Blutke
(German Research Center for Environmental Health)
- Katrin Fischer
(German Research Center for Environmental Health)
- Timo Dirk Müller
(German Research Center for Environmental Health)
- Katharina Kessler
(German Center for Diabetes Research (DZD)
German Institute of Human Nutrition Potsdam-Rehbruecke
Charité University of Medicine
University of Cambridge)
- Torsten Schöneberg
(University of Leipzig)
- Doreen Thor
(University of Leipzig)
- Silke Hornemann
(German Center for Diabetes Research (DZD)
German Institute of Human Nutrition Potsdam-Rehbruecke)
- Michael Kruse
(German Institute of Human Nutrition Potsdam-Rehbruecke
Charité University of Medicine)
- Peter Nawroth
(German Research Center for Environmental Health
Heidelberg University Hospital
German Center for Diabetes Research (DZD))
- Olga Pivovarova-Ramich
(German Center for Diabetes Research (DZD)
German Institute of Human Nutrition Potsdam-Rehbruecke
Charité University of Medicine
German Institute of Human Nutrition Potsdam-Rehbruecke)
- Andreas Friedrich Hermann Pfeiffer
(German Center for Diabetes Research (DZD)
German Institute of Human Nutrition Potsdam-Rehbruecke
Charité University of Medicine)
- Michael Sattler
(German Research Center for Environmental Health)
- Matthias Blüher
(University of Leipzig)
- Stephan Herzig
(German Research Center for Environmental Health
Heidelberg University Hospital
Technical University Munich
German Center for Diabetes Research (DZD))
Abstract
The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.
Suggested Citation
Anastasia Georgiadi & Valeria Lopez-Salazar & Rabih El- Merahbi & Rhoda Anane Karikari & Xiaochuan Ma & André Mourão & Katarina Klepac & Lea Bühler & Ana Jimena Alfaro & Isabell Kaczmarek & Adam Linfo, 2021.
"Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue,"
Nature Communications, Nature, vol. 12(1), pages 1-21, December.
Handle:
RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22579-1
DOI: 10.1038/s41467-021-22579-1
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