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Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization
Open accessAbstract
Obesity-associated low-grade inflammation underlies insulin resistance and associated metabolic comorbidities, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease. Excessive ectopic fat deposition in obesity causes disorders of energy homeostasis and low-grade chronic inflammation in metabolic tissues. In particular, obesity-induced recruitment and activation of adipose tissue macrophages play a key role in the pathogenesis of insulin resistance and T2D. Therefore, treatment options for energy metabolism and macrophage polarization in obese subjects are needed. Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion by inhibiting renal glucose reabsorption, thereby having subsequent anti-hyperglycemic effects and reducing body weight. We recently reported that the SGLT2 inhibitor empagliflozin increases fat utilization and browning in white adipose tissue and attenuates obesity-induced inflammation and insulin resistance by activating M2 macrophages. Thus, this review focuses on the beneficial effects of empagliflozin in energy homeostasis and obesity-related inflammation and insulin resistance.
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“whereas both dapagliflozin and empagliflozin were able to reduce liver lipid content in people with type 2 diabetes with (dapagliflozin [153,154]) or both with and without MASLD (empagliflozin [98]).”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [154]
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Metadata
- Authors
- Xu, L., & Ota, T.
- Affiliations
- Kanazawa University (JP)
- Corresponding author
- Ota, Tsuguhito
- Venue
- Adipocyte
- Publisher
- Informa UK Limited
- Published
- 2017-12-11
- Volume
- 7
- Issue
- 2
- Pages
- 1-8
- ISSN
- 2162-3945 (ISSN-L)
- 2162-397X
- PMC
- PMC6152529
- OpenAlex
- W2775166788
- Cited by
- 134
- References
- 63
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 21 · 2023: 27 · 2022: 25 · 2021: 14 · 2020: 18 · 2019: 5 · 2018: 4
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Adipocyte (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (16H03035)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- SGLT2 inhibitors, empagliflozin, obesity, insulin resistance, fat browning, white adipose tissue, macrophage polarization, M2 macrophages, low-grade inflammation, type 2 diabetes, non-alcoholic fatty liver disease, energy homeostasis, ectopic fat deposition, urinary glucose excretion
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Animals, Adipose Tissue, Brown, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Macrophage Activation, Macrophages, Obesity, Non-alcoholic Fatty Liver Disease
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