MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity.
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.
Westcott
Daniel J
DJ
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
Delproposto
Jennifer B
JB
Geletka
Lynn M
LM
Wang
Tianyi
T
Singer
Kanakadurga
K
Saltiel
Alan R
AR
Lumeng
Carey N
CN
D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D001212:Asialoglycoproteins / Q000502:physiology*; D001823:Body Composition; D002448:Cell Adhesion; D002465:Cell Movement; D004041:Dietary Fats / Q000008:administration & dosage; D018149:Glucose Intolerance / Q000209:etiology; D007249:Inflammation / Q000209:etiology*; D007333:Insulin Resistance; D037181:Lectins, C-Type / Q000502:physiology*; D016256:Lewis X Antigen / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology*; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D054390:Receptors, CCR2 / Q000502:physiology
D001212:Asialoglycoproteins; C515335:Ccr2 protein, mouse; C064720:Clec10a protein, mouse; D004041:Dietary Fats; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D008565:Membrane Proteins; D054390:Receptors, CCR2