Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation Factor 3 in Adipose Tissue Macrophages.
Yun BuKatsuhide OkunishiSatomi YogosawaKouichi MizunoMaria Johnson IrudayamChester W BrownTetsuro IzumiPublished in: Diabetes (2018)
Previous genetic studies in mice have shown that functional loss of activin receptor-like kinase 7 (ALK7), a type I transforming growth factor-β receptor, increases lipolysis to resist fat accumulation in adipocytes. Although growth/differentiation factor 3 (GDF3) has been suggested to function as a ligand of ALK7 under nutrient-excess conditions, it is unknown how GDF3 production is regulated. Here, we show that a physiologically low level of insulin converts CD11c- adipose tissue macrophages (ATMs) into GDF3-producing CD11c+ macrophages ex vivo and directs ALK7-dependent accumulation of fat in vivo. Depletion of ATMs by clodronate upregulates adipose lipases and reduces fat mass in ALK7-intact obese mice, but not in their ALK7-deficient counterparts. Furthermore, depletion of ATMs or transplantation of GDF3-deficient bone marrow negates the in vivo effects of insulin on both lipolysis and fat accumulation in ALK7-intact mice. The GDF3-ALK7 axis between ATMs and adipocytes represents a previously unrecognized mechanism by which insulin regulates both fat metabolism and mass.
Keyphrases
- adipose tissue
- insulin resistance
- advanced non small cell lung cancer
- type diabetes
- high fat diet
- transforming growth factor
- bone marrow
- high fat diet induced
- glycemic control
- stem cells
- transcription factor
- gene expression
- epidermal growth factor receptor
- signaling pathway
- dna methylation
- metabolic syndrome
- skeletal muscle
- case control
- binding protein
- nk cells