The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice
Open accessAbstract
Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion (UGE), leading to blood glucose reductions and weight loss. However, the impacts of SGLT2 inhibition on energy homeostasis and obesity-induced insulin resistance are less well known. Here, we show that empagliflozin, a SGLT2 inhibitor, enhanced energy expenditure and attenuated inflammation and insulin resistance in high-fat-diet-induced obese (DIO) mice. C57BL/6J mice were pair-fed a high-fat diet (HFD) or a HFD with empagliflozin for 16weeks. Empagliflozin administration increased UGE in the DIO mice, whereas it suppressed HFD-induced weight gain, insulin resistance, and hepatic steatosis. Moreover, empagliflozin shifted energy metabolism towards fat utilization, elevated AMP-activated protein kinase and acetyl-CoA carbolxylase phosphorylation in skeletal muscle, and increased hepatic and plasma fibroblast growth factor 21 levels. Importantly, empagliflozin increased energy expenditure, heat production, and the expression of uncoupling protein 1 in brown fat and in inguinal and epididymal white adipose tissue (WAT). Furthermore, empagliflozin reduced M1-polarized macrophage accumulation while inducing the anti-inflammatory M2 phenotype of macrophages within WAT and liver, lowering plasma TNFα levels and attenuating obesity-related chronic inflammation. Thus, empagliflozin suppressed weight gain by enhancing fat utilization and browning and attenuated obesity-induced inflammation and insulin resistance by polarizing M2 macrophages in WAT and liver.
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Citations
Cites
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Cited by
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SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control
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Metadata
- Authors
- Xu, L., Nagata, N., Nagashimada, M., Zhuge, F., Ni, Y., Chen, G., Mayoux, E., Kaneko, S., & Ota, T.
- Venue
- EBioMedicine
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 20
- Pages
- 137-149
- ISSN
- 2352-3964 (ISSN-L)
- OpenAlex
- W2619744261
- Cited by
- 493
- References
- 17
- FWCI
- 20.40
- Type
- journal article
- Language
- en
- Open access
- gold
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- Xu, L., Nagata, N., Nagashimada, M., Zhuge, F., Ni, Y., Chen, G., Mayoux, E., Kaneko, S., & Ota, T. (2017). SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice. EBioMedicine. https://doi.org/10.1016/j.ebiom.2017.05.028
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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