Empagliflozin Treatment Attenuates Hepatic Steatosis by Promoting White Adipose Expansion in Obese TallyHo Mice.

Autor:	Kurtz R; Department of Human Science, Georgetown University Medical Center, Washington, DC 20057, USA., Libby A; Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80012, USA., Jones BA; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA., Myakala K; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA., Wang X; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA., Lee Y; Department Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.; Center for Translational Imaging, Georgetown University Medical Center, Washington, DC 20057, USA., Knoer G; Department Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA., Lo Cascio JN; Department of Human Science, Georgetown University Medical Center, Washington, DC 20057, USA., McCormack M; Department Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA., Nguyen G; Department of Human Science, Georgetown University Medical Center, Washington, DC 20057, USA., Choos END; Department of Human Science, Georgetown University Medical Center, Washington, DC 20057, USA., Rodriguez O; Department Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.; Center for Translational Imaging, Georgetown University Medical Center, Washington, DC 20057, USA., Rosenberg AZ; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Ranjit S; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA.; Microscopy & Imaging Shared Resources, Georgetown University Medical Center, Washington, DC 20057, USA., Albanese C; Department Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.; Center for Translational Imaging, Georgetown University Medical Center, Washington, DC 20057, USA.; Department of Radiology, Georgetown University Medical Center, Washington, DC 20057, USA., Levi M; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA., Ecelbarger CM; Department of Medicine, Georgetown University Medical Center, Washington, DC 20057, USA., Shepard BD; Department of Human Science, Georgetown University Medical Center, Washington, DC 20057, USA.
Jazyk:	angličtina
Zdroj:	International journal of molecular sciences [Int J Mol Sci] 2022 May 18; Vol. 23 (10). Date of Electronic Publication: 2022 May 18.
DOI:	10.3390/ijms23105675
Abstrakt:	Sodium-glucose co-transporters (SGLTs) serve to reabsorb glucose in the kidney. Recently, these transporters, mainly SGLT2, have emerged as new therapeutic targets for patients with diabetes and kidney disease; by inhibiting glucose reabsorption, they promote glycosuria, weight loss, and improve glucose tolerance. They have also been linked to cardiac protection and mitigation of liver injury. However, to date, the mechanism(s) by which SGLT2 inhibition promotes systemic improvements is not fully appreciated. Using an obese TallyHo mouse model which recapitulates the human condition of diabetes and nonalcoholic fatty liver disease (NAFLD), we sought to determine how modulation of renal glucose handling impacts liver structure and function. Apart from an attenuation of hyperglycemia, Empagliflozin was found to decrease circulating triglycerides and lipid accumulation in the liver in male TallyHo mice. This correlated with lowered hepatic cholesterol esters. Using in vivo MRI analysis, we further determined that the reduction in hepatic steatosis in male TallyHo mice was associated with an increase in nuchal white fat indicative of "healthy adipose expansion". Notably, this whitening of the adipose came at the expense of brown adipose tissue. Collectively, these data indicate that the modulation of renal glucose handling has systemic effects and may be useful as a treatment option for NAFLD and steatohepatitis.
Databáze:	MEDLINE
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