# Editorial: Wnt signaling in endocrine and metabolic disorders

Frédéric Cailotto, Gaetano Santulli

<figure><img src="image_1.png" /></figure>

## To cite this version:

Frédéric Cailotto, Gaetano Santulli. Editorial: Wnt signaling in endocrine and metabolic disorders. Frontiers in Endocrinology, 2023, 14, pp.1254977. 10.3389/fendo.2023.1254977. hal-04284717

HAL Id: hal-04284717

https://hal.univ-lorraine.fr/hal-04284717

Submitted on 14 Nov 2023

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_3.png" /></figure>

Check for updates

OPEN ACCESS

EDITED AND REVIEWED BY
Ralf Jockers,
Université Paris Cité, France

*CORRESPONDENCE
Gaetano Santulli
gsantulli001@gmail.com

RECEIVED 08 July 2023
ACCEPTED 24 July 2023
PUBLISHED 07 August 2023

CITATION
Cailotto F and Santulli G (2023)
Editorial: Wnt signaling in endocrine and metabolic disorders.
Front. Endocrinol. 14:1254977.
doi: 10.3389/fendo.2023.1254977

COPYRIGHT
© 2023 Cailotto and Santulli. This is an open-access article distributed under the terms of the [Creative Commons Attribution License (CC BY)](https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

# Editorial: Wnt signaling in endocrine and metabolic disorders

Frederic Cailotto¹ and Gaetano Santulli²,³*

¹UMR7365 Ingénierie Moléculaire et Physiopathologie Articulaire (IMOPA) Centre National de la Recherche Scientifique - Université de Lorraine (CNRS-UL), Biopôle de l'Université de Lorraine, Vandœuvre-lès-Nancy, France, ²Department of Medicine, Wilf Family Cardiovascular Research Institute, Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, NY, United States, ³Department of Molecular Pharmacology, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Einstein Institute for Aging Research, Institute for Neuroimmunology and Inflammation (INI), Albert Einstein College of Medicine, New York, NY, United States

KEYWORDS

Wnt, metabolism, endocrinology & metabolism, Wnt/b-catenin, endocrinology, microRNA, Alzheimer's disease, cancer

## Editorial on the Research Topic

### Wnt signaling in endocrine and metabolic disorders

The present Research Topic, entitled "Wnt signaling in endocrine and metabolic disorders" aims to emphasize the functional role of the Wnt signaling pathway in human endocrinology, focusing on metabolic disease. Endocrine and metabolic disorders encompass a wide range of conditions affecting various organ systems and physiological processes. The Wnt signaling pathway, originally recognized for its role in embryonic development and tissue homeostasis (1, 2), has emerged as a crucial player in the pathogenesis of several human disorders, including cancer (3, 4), and greatly contributes to disease progression and potential therapeutic implications (5-7).

The first study in this Research Topic clarified that one of the mechanisms by which the "Modified Qing' E Formula" (MQEF), used for more than 1,300 years in China as a treatment for lumbodynia, may exert its therapeutic effect on steroid-induced ischemic necrosis of the femoral head, is through targeting exosomal microRNAs (miRNAs) to regulate multiple signaling pathways, including Wnt, PI3K-Akt, and MAPK (Zhu et al.). In another original report investigating miRNAs and Wnt signaling, Tripathi et al. demonstrate that miR-539-3p overexpression in osteoblasts downregulates several components of the Wnt signaling pathway and deteriorates trabecular microarchitecture, leading to decreased bone formation in ovariectomized mice. In the third original article in our Research Topic, a group of investigators led by Xiaolin Tu found that the small molecule C91 (CHIR99021) promotes osteogenic differentiation of bone marrow stromal cells via the activation of Wnt signaling (Wang et al.).

Vilaseca et al. provide an interesting overview of the functional roles of estrogen deficiency in the processes involved in the development of Alzheimer's disease, including Wnt signaling and glucose transport in the brain, amyloid precursor protein processing to form senile plaques, and Tau phosphorylation forming neurofibrillary tangles.

A very comprehensive review concludes our Research Topic: Franco et al. elegantly explain the main differences between the physiological roles of canonical Wnt signaling
(essential for cell growth, tissue remodeling, and organ formation) and its pathological involvement in the development of several human diseases, including cancer. Correctly interpreting the molecular bases of Wnt signaling and metabolism, ideally in a cell-type and tissue-specific manner (Franco et al.; 8–10), may provide formidable knowledge to biomedical scientists and clinicians, holding the promise of producing novel therapies.

In conclusion, understanding the intricate interplay between Wnt signaling and endocrine/metabolic disorders holds great promise for the development of targeted therapies and improved patient outcomes.

## Author contributions

FC: Writing - review & editing. GS: Writing - original draft

## Funding

The Santulli Lab is supported in part by the National Institutes of Health (NIH) (the National Heart, Lung, and Blood Institute [NHLBI: R01-HL164772, R01-HL159062, R01-HL146691, and T32-HL144456 to GS] and the National Institute of Diabetes and

Digestive and Kidney Diseases [NIDDK: R01-DK123259 and R01-DK033823 to GS]); the National Center for Advancing Translational Sciences (NCATS: UL1-TR002556-06 to GS); the Diabetes Action Research and Education Foundation (to GS); and the Monique Weill-Caulier and Irma T. Hirschl Trusts (to GS). FC is supported by grants from the Fondation pour la Recherche Médicale (FRM, n° REP202210016152).

## Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

## Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

## References

1. Li D, Sun J, Zhong TP. Wnt signaling in heart development and regeneration. *Curr Cardiol Rep* (2022) 24(10):1425-38.

2. Steinhart Z, Angers S. Wnt signaling in development and tissue homeostasis. *Development* (2018) 145(11):dev146589.

3. Zhou Y, Xu J, Luo H, Meng X, Chen M, Zhu D. Wnt signaling pathway in cancer immunotherapy. *Cancer Lett* (2022) 525:84-96.

4. Bugter JM, Fenderico N, Maurice MM. Mutations and mechanisms of WNT pathway tumour suppressors in cancer. *Nat Rev Cancer* (2021) 21(1):5-21.

5. Rim EY, Clevers H, Nusse R. The Wnt pathway: from signaling mechanisms to synthetic modulators. *Annu Rev Biochem* (2022) 91:571-98.

6. Albrecht LV, Tejeda-Munoz N, De Robertis EM. Cell biology of canonical Wnt signaling. *Annu Rev Cell Dev Biol* (2021) 37:369-89.

7. Akoumianakis I, Polkinghorne M, Antoniades C. Non-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications. *Nat Rev Cardiol* (2022) 19(12):783-97.

8. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. *Cell* (2012) 149 (6):1192-205.

9. Chen X, Tan H, Xu J, Tian Y, Yuan Q, Zuo Y, et al. Klotho-derived peptide 6 ameliorates diabetic kidney disease by targeting Wnt/beta-catenin signaling. *Kidney Int* (2022) 102(3):506-20.

10. Aamir K, Khan HU, Sethi G, Hossain MA, Arya A. Wnt signaling mediates TLR pathway and promote unrestrained adipogenesis and metaflammation: Therapeutic targets for obesity and type 2 diabetes. *Pharmacol Res* (2020) 152:104602.