CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors

Abstract

Adipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or antiinflammatory cytokines. Here, we show that M2-like macrophages in adipose tissue regulate systemic glucose homeostasis by inhibiting adipocyte progenitor proliferation via the CD206/ TGFβ signaling pathway. We show that adipose tissue CD206 + cells are primarily M2-like macrophages, and ablation of CD206 + M2-like macrophages improves systemic insulin sensitivity, which was associated with an increased number of smaller adipocytes. Mice genetically engineered to have reduced numbers of CD206 + M2-like macrophages show a down-regulation of TGFβ signaling in adipose tissue, together with up-regulated proliferation and differentiation of adipocyte progenitors. Our findings indicate that CD206 + M2-like macrophages in adipose tissues create a microenvironment that inhibits growth and differentiation of adipocyte progenitors and, thereby, control adiposity and systemic insulin sensitivity.

Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages

“…Recently, resident CD206 + ATMs were suggested to inhibit adipogenesis and promote adipocyte hypertrophy and insulin resistance [17]. This would fit with our data early in HFD feeding at 7-14d, showing increased resident ATM quantity with no change in PAs (Figure 1E, Supplemental Figure S1).…”

“…These studies support the importance of M2-like tissue resident ATMs in tissue homeostasis. Indeed, ATMs with M2-like profiles are implicated in regulation of adipocyte hypertrophy and extracellular matrix remodeling, both of which are important for maintaining metabolically healthy adipose tissue [17–19]. Thus, phenotypic changes in both CD11c + and resident ATMs with obesity may together strongly influence adipose tissue health and contribute to development of insulin resistance.…”

Astaxanthin stimulates mitochondrial biogenesis in insulin resistant muscle via activation of AMPK pathway

“…Tissues for the western blot analysis were quickly frozen in liquid nitrogen and preserved at −80°C until the analysis. The western blot analysis was performed as described previously . Briefly, the tissues for western blotting were homogenized in lysis buffer containing 25 mM Tris–HCl (pH 7.4), 10 mM Na 3 VO 4 , 100 mM NaF, 50 mM Na 4 P2O 7 , 10 mM EDTA, 0.2% leupeptin (5 mg/mL), 0.5% aprotinin (5 mg/mL), 2 mM phenylmethylsulfonyl fluoride, and 1% Nonidet P‐40, using a Multi‐Beads Shocker cell disrupter (Yasui Kikai Corporation, Osaka, Japan).…”

“…For the intraperitoneal glucose tolerance test, the mice were fasted for 18 h and were administered an intraperitoneal injection of glucose; 1 mg/g body weight (BW). For the intraperitoneal insulin tolerance test, mice fasted for 2–3 h and were administered an intraperitoneal injection of human insulin (0.8 units/kg BW for the mice fed NC and 1.2 units/kg BW for the mice fed HFD . Blood samples were then collected from the tail vein at 0, 15, 30, 45, 60, 90, and 120 min after the injection for glucose/insulin measurement.…”

Genetic Models of Macrophage Depletion

“…Depletion of CD206 + macrophages resulted in an increased number of smaller adipocytes, as well as an amelioration of systemic insulin sensitivity. The results indicated that CD206 + macrophages may contribute to a special niche in adipose tissues which functions to suppress the growth and differentiation of adipocyte progenitors (60). …”