Imperial College London
Alternate

DrIsabelleLeclerc

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3354i.leclerc

 
 
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Location

 

323ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Parks:2022:rs.3.rs-2136059/v1,
author = {Parks, SZ and Rutter, GA and Leclerc, I},
doi = {rs.3.rs-2136059/v1},
title = {Effects of whole-body sorcin knockout on body weight and hypothalamic ER-stress in C57BL/6 male mice fed a westernized diet},
url = {http://dx.doi.org/10.21203/rs.3.rs-2136059/v1},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title>        <jats:p>Background  Soluble Resistance Related Calcium Binding Protein (sorcin) is a calcium (Ca<jats:sup>2+</jats:sup>) binding protein which has been shown to play a role in maintaining intracellular endoplasmic reticulum (ER) Ca<jats:sup>2+</jats:sup> stores and lowering ER stress. Recently, our lab has demonstrated that sorcin expression was downregulated in the islets of Langerhans of mice fed a high-fat diet or in human islets incubated with the saturated fatty acid palmitate. We also showed that overexpression of sorcin under control of the rat insulin promoter (RIP7) in C57BL/6J mice, or whole body sorcin deletion in 129S1/SvImJ mice, improves or impairs insulin secretion and pancreatic β-cell function respectively. The mechanisms behind this beneficial role of sorcin in the pancreatic β-cell might depend on protection against lipotoxic endoplasmic reticulum (ER) stress through improved ER Ca<jats:sup>2+</jats:sup> dynamics and activation of the Activating Transcription Factor 6 (ATF6) branch of the unfolded protein response (UPR). Whether sorcin is also implicated in hypothalamic ER stress during the progression of obesity is unknown.Aim To investigate a potential role of sorcin in hypothalamic ER stress, leptin resistance, hyperphagia and obesity.Methods Whole-body sorcin null mice, backcrossed onto the C57BL/6J genetic background, were used. Body weight, food intake and EchoMRI body composition were measured in vivo whereas qRT-PCR analysis of sorcin and ER stress markers expression were performed on the arcuate nucleus of the hypothalamus. Leptin signalling through STAT3 phosphorylation was measured by Western blots on sorcin-null HEK293 cells, engineered by CRISPR/Cas9, and transfected with leptin receptor (LepRb).Results Sorcin expression was not influenced in the arcuate nucleus (ARC) of the hypothalamus by diet-induced obesity. Whole-body sorcin a
AU  - Parks,SZ
AU  - Rutter,GA
AU  - Leclerc,I
DO  - rs.3.rs-2136059/v1
PY  - 2022///
TI  - Effects of whole-body sorcin knockout on body weight and hypothalamic ER-stress in C57BL/6 male mice fed a westernized diet
UR  - http://dx.doi.org/10.21203/rs.3.rs-2136059/v1
ER  -
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