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Article

The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B

by
Pierre-Jean Cornejo
1,
Bastien Vergoni
1,
Mickaël Ohanna
2,
Brice Angot
1,
Teresa Gonzalez
1,3,
Jennifer Jager
1,
Jean-François Tanti
1 and
Mireille Cormont
1,*
1
Université Côte d’Azur, Inserm, C3M, Team “Molecular and Cellular Physiopathology of Obesity and Diabetes”, 06204 Nice, France
2
Université Côte d’Azur, Inserm, C3M, “Team Microenvironnement, Signalisation et Cancer”, 06204 Nice, France
3
Aix Marseille Université, Inserm, INRAE, C2VN, 13385 Marseille, France
*
Author to whom correspondence should be addressed.
Cells 2022, 11(16), 2581; https://doi.org/10.3390/cells11162581
Submission received: 17 June 2022 / Revised: 2 August 2022 / Accepted: 5 August 2022 / Published: 19 August 2022
(This article belongs to the Special Issue The Role of Adipose Tissue in Metabolic Diseases and Beyond)
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Abstract

Metabolic stresses alter the signaling and actions of insulin in adipocytes during obesity, but the molecular links remain incompletely understood. Members of the microRNA-34 (miR-34 family play a pivotal role in stress response, and previous studies showed an upregulation of miR-34a in adipose tissue during obesity. Here, we identified miR-34a as a new mediator of adipocyte insulin resistance. We confirmed the upregulation of miR-34a in adipose tissues of obese mice, which was observed in the adipocyte fraction exclusively. Overexpression of miR-34a in 3T3-L1 adipocytes or in fat pads of lean mice markedly reduced Akt activation by insulin and the insulin-induced glucose transport. This was accompanied by a decreased expression of VAMP2, a target of miR-34a, and an increased expression of the tyrosine phosphatase PTP1B. Importantly, PTP1B silencing prevented the inhibitory effect of miR-34a on insulin signaling. Mechanistically, miR-34a decreased the NAD+ level through inhibition of Naprt and Nampt, resulting in an inhibition of Sirtuin-1, which promoted an upregulation of PTP1B. Furthermore, the mRNA expression of Nampt and Naprt was decreased in adipose tissue of obese mice. Collectively, our results identify miR-34a as a new inhibitor of insulin signaling in adipocytes, providing a potential pathway to target to fight insulin resistance.
Keywords: obesity; insulin resistance; adipose tissue; GLUT4; VAMP2; NAD obesity; insulin resistance; adipose tissue; GLUT4; VAMP2; NAD

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MDPI and ACS Style

Cornejo, P.-J.; Vergoni, B.; Ohanna, M.; Angot, B.; Gonzalez, T.; Jager, J.; Tanti, J.-F.; Cormont, M. The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B. Cells 2022, 11, 2581. https://doi.org/10.3390/cells11162581

AMA Style

Cornejo P-J, Vergoni B, Ohanna M, Angot B, Gonzalez T, Jager J, Tanti J-F, Cormont M. The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B. Cells. 2022; 11(16):2581. https://doi.org/10.3390/cells11162581

Chicago/Turabian Style

Cornejo, Pierre-Jean, Bastien Vergoni, Mickaël Ohanna, Brice Angot, Teresa Gonzalez, Jennifer Jager, Jean-François Tanti, and Mireille Cormont. 2022. "The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B" Cells 11, no. 16: 2581. https://doi.org/10.3390/cells11162581

APA Style

Cornejo, P.-J., Vergoni, B., Ohanna, M., Angot, B., Gonzalez, T., Jager, J., Tanti, J.-F., & Cormont, M. (2022). The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B. Cells, 11(16), 2581. https://doi.org/10.3390/cells11162581

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