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

Adipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory 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

トップダウン法とボトムアップ法によるCO2フラックス推定値の比較 ～シベリア･ヤクーツクでのケーススタディ～

第6回極域科学シンポジウム分野横断セッション：[IA] 急変する北極気候システム及びその全球的な影響の総合的解明―GRENE北極気候変動研究事業研究成果報告2015―11月19日（木）　国立極地研究所１階交流アトリウ

Modelling of greenhouse gases and related species in the Arctic environment

Numerical modelling of greenhouse gases (GHGs) has become an integral part for understanding amplitude and variability in their concentrations and sources/sinks, atmospheric transport and climate implication. Carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) are the three major species studied in the Arctic Green Network of Excellence (GRENE), a programme funded by the Ministry of Education, Culture, Sports, Science and Technology-Japan (MEXT). In addition some of the ozone depleting substances, e.g., methyl chloroform (CH3CCl3), have provided strong constrain on the global mean abundance of hydroxyl (OH) radical and its relative abundance in the northern and southern hemispheres (NH/SH OH ratio; Patra et al., 2014). Being the main destroyer of many of the GHGs (e.g., CH4, hydrofluorocarbons), accurate quantification of OH was needed for estimation of CH4 sink in the troposphere, and thus the sources on the Earth’s surface by inverse modelling (Patra et al., 2016). OH is also contributes to chemical production of CO2, up to ~50% of land/ocean sink. The modellers are also required to verify the accuracy of model transport using tracers of short (e.g., 222Rn with 3.8 days) and long (SF6 with 3200 yrs) lifetimes. For understanding of the carbon cycle science, analyses of oxygen (O2/N2) variability are also conducted. List of chemistry-transport models (CTMs) participating in the Arctic GRENE programme are given Table 1.O08-05, Final Symposium on GRENE-Arctic Climate Change Research Project = GRENE北極気候変動研究事業研究成果報告会 (3-4 March, 2016, National Institute for Japanese Language and Linguistics, Tachikawa, Japan

Exogenous Cytokine-Free Differentiation of Human Pluripotent Stem Cells into Classical Brown Adipocytes

We previously established a method for a directed differentiation of human pluripotent stem cells into classical brown adipocytes (BA) by forming aggregates via massive floating culture in the presence of a specific cytokine cocktail. However, use of recombinant cytokines requires significant cost. Moreover, an enforced differentiation by exogenously added cytokines may amend skewed differentiation propensity of patient’s pluripotent stem cells, providing unsatisfactory disease models. Therefore, an exogenous cytokine-free method, where cytokines required for differentiation are provided in an auto/paracrine manner mimicking natural developmental process, is beneficial. Here we show that, if human pluripotent stem cells are cultured as size-controlled spheroids (100–120 µm radius, 2000–2500 cells/spheroid) in a mutually segregated manner with half-change of the medium every other day, they differentiate into classical BA via an authentic MYF5-positive myoblast route in the absence of exogenous cytokines. Differentiated BA exerted thermogenic activity in transplanted mice in response to beta-adrenergic receptor agonist stimuli. The cytokine-free differentiation method has further advantages in exploring BATokines, BA-derived physiologically active substances. Indeed, we have found that BA produces an unknown small (<1000 Da), highly hydrophilic molecule that augments insulin secretion from pancreatic beta cells. Our upgraded technique will contribute to an advancement of stem cell study for diverse purposes