Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization

Adipocyte. 2018;7(2):121-128. doi: 10.1080/21623945.2017.1413516. Epub 2018 Jan 29.

Abstract

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.

Keywords: adipose tissue macrophage; empagliflozin; fat browning; inflammation; insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipose Tissue, Brown / drug effects*
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Humans
  • Insulin Resistance*
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*

Substances

  • Sodium-Glucose Transporter 2 Inhibitors