MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity

J Exp Med. 2009 Dec 21;206(13):3143-56. doi: 10.1084/jem.20091333. Epub 2009 Dec 7.

Abstract

Adipose tissue macrophages (ATMs) play a critical role in obesity-induced inflammation and insulin resistance. Distinct subtypes of ATMs have been identified that differentially express macrophage galactose-type C-type lectin 1 (MGL1/CD301), a marker of alternatively activated macrophages. To evaluate if MGL1 is required for the anti-inflammatory function of resident (type 2) MGL1(+) ATMs, we examined the effects of diet-induced obesity (DIO) on inflammation and metabolism in Mgl1(-/-) mice. We found that Mgl1 is not required for the trafficking of type 2 ATMs to adipose tissue. Surprisingly, obese Mgl1(-/-) mice were protected from glucose intolerance, insulin resistance, and steatosis despite having more visceral fat. This protection was caused by a significant decrease in inflammatory (type 1) CD11c(+) ATMs in the visceral adipose tissue of Mgl1(-/-) mice. MGL1 was expressed specifically in 7/4(hi) inflammatory monocytes in the blood and obese Mgl1(-/-) mice had lower levels of 7/4(hi) monocytes. Mgl1(-/-) monocytes had decreased half-life after adoptive transfer and demonstrated decreased adhesion to adipocytes indicating a role for MGL1 in the regulation of monocyte function. This study identifies MGL1 as a novel regulator of inflammatory monocyte trafficking to adipose tissue in response to DIO.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / physiology
  • Adipose Tissue / pathology*
  • Animals
  • Asialoglycoproteins / physiology*
  • Body Composition
  • Cell Adhesion
  • Cell Movement
  • Dietary Fats / administration & dosage
  • Glucose Intolerance / etiology
  • Inflammation / etiology*
  • Insulin Resistance*
  • Lectins, C-Type / physiology*
  • Lewis X Antigen / biosynthesis
  • Macrophages / physiology
  • Male
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / physiology*
  • Obesity / complications*
  • Obesity / metabolism
  • Receptors, CCR2 / physiology

Substances

  • Asialoglycoproteins
  • Ccr2 protein, mouse
  • Clec10a protein, mouse
  • Dietary Fats
  • Lectins, C-Type
  • Lewis X Antigen
  • Membrane Proteins
  • Receptors, CCR2