SGK1 activation exacerbates diet-induced obesity, metabolic syndrome and hypertension

in Journal of Endocrinology
Authors:
Catalina Sierra-Ramos Department of Basic Medical Sciences, Institute of Biomedical Technologies and Center for Biomedical Research of the Canary Islands (CIBICAN), Universidad de La Laguna, Tenerife, Spain

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Silvia Velazquez-Garcia Department of Basic Medical Sciences, Institute of Biomedical Technologies and Center for Biomedical Research of the Canary Islands (CIBICAN), Universidad de La Laguna, Tenerife, Spain

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Arianna Vastola-Mascolo Department of Basic Medical Sciences, Institute of Biomedical Technologies and Center for Biomedical Research of the Canary Islands (CIBICAN), Universidad de La Laguna, Tenerife, Spain

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Guadalberto Hernández Department of Basic Medical Sciences, Institute of Biomedical Technologies and Center for Biomedical Research of the Canary Islands (CIBICAN), Universidad de La Laguna, Tenerife, Spain

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Nourdine Faresse Institute of Anatomy, University of Zurich, Zurich, Switzerland

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Diego Alvarez de la Rosa Department of Basic Medical Sciences, Institute of Biomedical Technologies and Center for Biomedical Research of the Canary Islands (CIBICAN), Universidad de La Laguna, Tenerife, Spain

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Correspondence should be addressed to D Alvarez de la Rosa: diego.alvarez@ull.edu.es

*(C Sierra-Ramos and S Velázquez-García contributed equally to this work)

†(N Faresse is now at DIVA Expertise, 1 Place Pierre Potier, Toulouse, France)

DOI:
https://doi.org/10.1530/JOE-19-0275
Volume/Issue:
Volume 244: Issue 1
Article Type:
Research Article
Page Range:
149–162
Online Publication Date:
Jan 2020
Copyright:
© 2020 Society for Endocrinology 2020
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The serum- and glucocorticoid-induced kinase 1 (SGK1) is a transcriptional target of steroid hormones including glucocorticoids or aldosterone in addition to other stimuli such as glucose. SGK1 is activated via phosphoinositide 3-kinase, placing it downstream of insulin signaling. SGK1 participates in the upregulation of kidney Na+ reabsorption by aldosterone and has been linked to obesity-related hypertension in humans. We hypothesized that a systemic increase in SGK1 activity may trigger a multiplicity of mechanisms leading to simultaneous development of the main conditions that characterize the metabolic syndrome (MetS), including hypertension. We used a transgenic mouse model made with a bacterial artificial chromosome containing the whole mouse Sgk1 gene modified to introduce an activating point mutation. Wild type or transgenic 14-week-old male mice were fed with standard chow diet or high-fat diet for up to 18 weeks. Development of the main features of MetS and hepatic steatosis were monitored, and in vitro adipocyte differentiation was studied. Our results show that transgenic animals under high-fat diet rapidly and markedly develop MetS characterized by obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. In addition, SGK1 gain-of-function accelerates the development of hepatic steatosis. Our study suggests that inappropriate SGK1 activity represents a risk factor in developing MetS with hypertension and related end-organ damage. Our data support SGK1 as a possible therapeutic target in MetS and related complications and provides a useful gain-of-function model for pre-clinical drug testing.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
14
Article Type:
Research Article
Received Date:
12 Sep 2019
Accepted Date:
10 Oct 2019
Print Publication Date:
01 Jan 2020
Online Publication Date:
Jan 2020
Keywords:
insulin resistance; blood pressure; serum and glucocorticoid-induced kinase; mouse model; fatty liver

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