Version 1
: Received: 7 August 2024 / Approved: 8 August 2024 / Online: 8 August 2024 (12:32:44 CEST)
How to cite:
Türküner, M. S.; Yazıcı, A.; Özcan, F. SIK2 Controls the Homeostatic Character of POMC Secretome Acutely in Response to Pharmacological ER Stress Induction. Preprints2024, 2024080611. https://doi.org/10.20944/preprints202408.0611.v1
Türküner, M. S.; Yazıcı, A.; Özcan, F. SIK2 Controls the Homeostatic Character of POMC Secretome Acutely in Response to Pharmacological ER Stress Induction. Preprints 2024, 2024080611. https://doi.org/10.20944/preprints202408.0611.v1
Türküner, M. S.; Yazıcı, A.; Özcan, F. SIK2 Controls the Homeostatic Character of POMC Secretome Acutely in Response to Pharmacological ER Stress Induction. Preprints2024, 2024080611. https://doi.org/10.20944/preprints202408.0611.v1
APA Style
Türküner, M. S., Yazıcı, A., & Özcan, F. (2024). SIK2 Controls the Homeostatic Character of POMC Secretome Acutely in Response to Pharmacological ER Stress Induction. Preprints. https://doi.org/10.20944/preprints202408.0611.v1
Chicago/Turabian Style
Türküner, M. S., Ayşe Yazıcı and Ferruh Özcan. 2024 "SIK2 Controls the Homeostatic Character of POMC Secretome Acutely in Response to Pharmacological ER Stress Induction" Preprints. https://doi.org/10.20944/preprints202408.0611.v1
Abstract
The neuronal etiology of obesity is centered around diet-induced inflammatory state in the arcuate nucleus of the hypothalamus which impairs the functionality of pro-opiomelanocortine neurons (POMCs) responsible for whole-body energy homeostasis and feeding behavior. Intriguingly, systemic salt inducible kinase 2 (SIK2) knockout mouse demonstrated reduced food intake and energy expenditure along with modestly dysregulated metabolic parameters suggesting a causal link between the absence of SIK2 activity in POMCs and the observed phenotype. To test this hypothesis, we conducted a comparative secretomics study from POMC neurons following pharmacologically induced endoplasmic reticulum (ER) stress induction, a hallmark of metabolic inflammation and POMC dysregulation in diet induced obese (DIO) mice. Our data provide significant in vitro evidence for the POMC specific SIK2 activity in controlling the energy metabolism and feeding in DIO mice by regulating the nature of related POMC secretome. Our data also suggests that under physiological stress conditions SIK2 may act as a gatekeeper for the secreted inflammatory factors and signaling molecules critical for cellular survival and energy homeostasis. On the other hand, in the absence of SIK2 gate opens leading to surge of inflammatory cytokines and apoptotic cues concomitant with the dysregulation of POMC neurons.
Keywords
SIK2; POMC; inflammation; neuronal secretome; ER stress; hypothalamic obesity
Subject
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
