Nascent shifts in renal cellular metabolism, structure, and function due to chronic empagliflozin in prediabetic mice

Author:

Shepard Blythe D.1ORCID,Chau Jennifer2,Kurtz Ryan1,Rosenberg Avi Z.3,Sarder Pinaki4,Border Samuel P.4,Ginley Brandon35,Rodriguez Olga67,Albanese Chris678,Knoer Grace7,Greene Aarenee2,De Souza Aline M. A.2ORCID,Ranjit Suman910,Levi Moshe9ORCID,Ecelbarger Carolyn M.2ORCID

Affiliation:

1. Department of Human Science, Georgetown University, Washington, District of Columbia, United States

2. Department of Medicine,Georgetown University, Washington, District of Columbia, United States

3. Department of Pathology, Johns Hopkins University, Baltimore, Maryland, United States

4. J Crayton Pruitt Department of Biomedical Engineering, University of Florida, Gainesville, Florida, United States

5. Department of Computational Cell Biology, Anatomy, and Pathology, State University of New York at Buffalo, Buffalo, New York, United States

6. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, United States

7. Center for Translational Imaging, Georgetown University, Washington, District of Columbia, United States

8. Department of Radiology, Georgetown University, Washington, District of Columbia, United States

9. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, District of Columbia, United States

10. Microscopy & Imaging Shared Resources, Georgetown University, Washington, District of Columbia, United States

Abstract

Renal protection afforded by sodium glucose transporter, type 2 inhibitors (SGLT2i), e.g., empagliflozin (EMPA) involves complex intertwined mechanisms. Using a novel mouse model of obesity with insulin resistance, the TallyHo/Jng (TH) mouse on a high-milk-fat diet (HMFD), we found subtle changes in metabolism including altered regulation of sodium transporters that line the renal tubule. New potential epigenetic determinants of metabolic changes relating to FOXO and cancer signaling pathways were elucidated from an altered urine exosomal microRNA signature.

Funder

Dekkers Endowed Chair in Human Science

American Heart Association

HHS | NIH | National Cancer Institute

HHS | NIH | National Center for Advancing Translational Sciences

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

J. Willard and Alice S. Marriott Foundation

Publisher

American Physiological Society

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1. Cellular and molecular mechanisms of antidiabetics beyond glycemic control;American Journal of Physiology-Cell Physiology;2024-07-01

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