Dataset Information

The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile.

ABSTRACT: The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM.

SUBMITTER: Aragon-Herrera A

PROVIDER: S-EPMC8847595 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile.

Aragón-Herrera Alana A Otero-Santiago Manuel M Anido-Varela Laura L Moraña-Fernández Sandra S Campos-Toimil Manuel M García-Caballero Tomás T Barral Luis L Tarazón Estefanía E Roselló-Lletí Esther E Portolés Manuel M Gualillo Oreste O Moscoso Isabel I Lage Ricardo R González-Juanatey José Ramón JR Feijóo-Bandín Sandra S Lago Francisca F

Frontiers in pharmacology 20220202

The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understandi ...[more]

PMID: 35185578

Similar Datasets

Project description:BackgroundDiabetic encephalopathy (DE) is a complication of diabetes that leads to cognitive and behavioral decline. Utilizing safe and effective complementary and alternative medications for its management is a wise choice. Previous studies have shown that GuanXinNing Tablet (GXNT), an oral preparation primarily derived from two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., exerts a beneficial neuroprotective effect. In this study, we explored the protective effects of GXNT on DE in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet, aiming to ascertain its significance and potential mechanisms.MethodsZDF rats were induced to develop type 2 diabetes (T2DM) with DE by a high-fat diet and treated with GXNT for 8 weeks until they were 20 weeks old. Throughout the experiment, the animals' vital parameters, such as body weight, were continuously monitored. Cognitive function was evaluated using the Y maze test. Biochemical kits were employed to analyze blood glucose, lipids, and vascular endothelial-related factors. Cerebrovascular lesions were assessed using magnetic resonance angiography (MRA) imaging. Brain lesions were evaluated using hematoxylin and eosin (H&E) staining and ultrastructure observation. IgG and albumin (ALB) leakage were detected using immunofluorescence.ResultsGXNT demonstrated an enhancement in the overall well-being of the animals. It notably improved cognitive and behavioral abilities, as demonstrated by extended retention time in the novel heterogeneous arm during the Y-maze test. GXNT effectively regulated glucose and lipid metabolism, reducing fasting and postprandial blood glucose, glycated hemoglobin (HbA1c), and total cholesterol (TC) levels. Additionally, it exhibited a protective effect on the vascular endothelium by reducing the serum TXB2/PGI2 ratio while elevating NO and PGI2 levels. Moreover, GXNT ameliorated stenosis and occlusion in cerebral vessel branches, increased the number of microvessels and neurons around the hippocampus, and improved microvascular occlusion in the cerebral cortex, along with addressing perivascular cell abnormalities. Immunofluorescence staining showed a decrease in the fluorescence intensity of IgG and ALB in the cerebral cortex.ConclusionsGXNT demonstrated a highly satisfactory protective effect on DE in ZDF rats. Its mechanism of action could be based on the regulation of glucolipid metabolism and its protective effect on the vascular endothelium.

Dataset Information

The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile.

Publications

The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets