SBP2 deficiency in adipose tissue macrophages drives insulin resistance in obesity

Sci Adv. 2019 Aug 14;5(8):eaav0198. doi: 10.1126/sciadv.aav0198. eCollection 2019 Aug.

Abstract

Proinflammatory activation and accumulation of adipose tissue macrophages (ATMs) are associated with increased risk of insulin resistance in obesity. Here, we described the previously unidentified role of selenocysteine insertion sequence-binding protein 2 (SBP2) in maintaining insulin sensitivity in obesity. SBP2 was suppressed in ATMs of diet-induced obese mice and was correlated with adipose tissue inflammation. Loss of SBP2 initiated metabolic activation of ATMs, inducing intracellular reactive oxygen species content and inflammasome, which subsequently promoted IL-1β-associated local proliferation and infiltration of proinflammatory macrophages. ATM-specific knockdown of SBP2 in obese mice promoted insulin resistance by increasing fat tissue inflammation and expansion. Reexpression of SBP2 improved insulin sensitivity. Last, an herbal formula that specifically induced SBP2 expression in ATMs can experimentally improve insulin sensitivity. Clinical observation revealed that it improved hyperglycemia in patients with diabetes. This study identified SBP2 in ATMs as a potential target in rescuing insulin resistance in obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Movement
  • Cell Proliferation
  • Drugs, Chinese Herbal / therapeutic use
  • Gene Knockout Techniques
  • Humans
  • Hyperglycemia / drug therapy
  • Inflammasomes / metabolism
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology*
  • Interleukin-1beta / metabolism
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Middle Aged
  • Obesity / pathology*
  • RNA-Binding Proteins / genetics*
  • Reactive Oxygen Species / metabolism
  • Selenocysteine / genetics
  • Young Adult

Substances

  • Drugs, Chinese Herbal
  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • RNA-Binding Proteins
  • Reactive Oxygen Species
  • SECIS-binding protein 2, mouse
  • Selenocysteine