Whole-tissue 3D imaging reveals intra-adipose sympathetic plasticity regulated by NGF-TrkA signal in cold-induced beiging

Sympathetic arborizations act as the essential efferent signals in regulating the metabolism of peripheral organs including white adipose tissues (WAT). However, whether these local neural structures would be of plastic nature, and how such plasticity might participate in specific metabolic events of WAT, remains largely uncharacterized. In this study, we exploit the new volume fluorescence-imaging technique to observe the significant, and also reversible, plasticity of intra-adipose sympathetic arborizations in mouse inguinal WAT in response to cold challenge. We demonstrate that this sympathetic plasticity depends on the cold-elicited signal of nerve growth factor (NGF) and TrkA receptor. Blockage of NGF or TrkA signaling suppresses intra-adipose sympathetic plasticity, and moreover, the cold-induced beiging process of WAT. Furthermore, we show that NGF expression in WAT depends on the catecholamine signal in cold challenge. We therefore reveal the key physiological relevance, together with the regulatory mechanism, of intra-adipose sympathetic plasticity in the WAT metabolism.

Mast cells promote the beiging of white adipose tissue from cold shock / 中华内分泌代谢杂志

This article is the translation of Mast Cells Promote Seasonal White Adipose Beiging in Humans, published in the Diabetes in May, 2017(Diabetes 2017,66:1237-1246), with the consent of Diabetes.This study mainly investigated the mechanism of the beiging of white adipose tissue(WAT).Studies in rodents suggested that cold shock and a number of immune mediators were important for the beiging of subcutaneous white adipose tissue (SC-WAT).This study observed the seasonal beiging of SC-WAT from lean humans, measured the gene expression of various immune cell markers, and performed multivariate analysis of the gene expression data to identify genes that could predict uncoupling protein-1(UCP-1) expression.The mechanism of the induction of UCP-1 from adipocytes by mast cells was also explored by in vitro experiment.The results showed that TIB64 mast cells responded to cold shock by releasing histamine and interleukin 4 (IL-4) which promoted the expression of UCP-1 and the lipolysis of 3T3-L1 adipocytes.Pharmacological block of the degranulation of mast cells potently inhibited the release of histamine and adipocyte UCP-1 mRNA induction by conditioned medium.In summary, mast cells are an important immune cell type in the beiging of WAT which sense colder temperatures, and release factors that promote UCP-1 expression.

Inhibition and mechanism of olanzapine on white adipose tissue beiging in mice / 中国药科大学学报

@#As one of the first-line antipsychotic drugs, olanzapine(OLA)inducing insulin resistance and metabolic disorder has become a serious clinical concern. This study aimed at investigating the effect of OLA on white adipose tissue(WAT)beiging as a potential mechanism behind its metabolism-disturbing effects. C57BL6/J mice were orally administered with low and high-dose OLA(4, 8 mg/kg, once daily)for 28 consecutive days; body weight and food intake were recorded every other day. Mice were subjected to glucose-tolerance test(GTT)and a cohort from each group was challenged with cold stress for 36 h before sacrifice. The perirenal, epididymal and inguinal WAT were carefully dissected, weighed and processed separately for hematoxylin-eosin staining, UCP-1 immunohistochemical and Western blot analysis. The results showed that OLA induced significant impairment in basal heat generation and glucose regulation. There were fewer beige adipocytes in the inguinal WAT after OLA treatment. The beiging of inguinal WAT in response to cold stress was significantly inhibited in OLA-treated mice. Mechanistically, OLA induced the activation of mTOR-Notch pathway, as evidenced by a significant increase in phosphorylated mammalian target of rapamycin(p-mTOR)and intracellular domain of Notch1(N1ICD)expression. Together, our study reveals that the inhibitory effects on WAT beiging may explain the propensity of OLA to induce metabolic disturbance, and mTOR-Notch pathway activation could play key roles in this effect. Future validation and elucidation of these novel findings are expected to provide novel insights into the metabolic risks of OLA and related second generation antipsychotics, which may lead to innovative intervention strategies in the clinic.