263-LB: Functional Inactivation of Mast Cell Enhances Subcutaneous Adipose Tissue Browning through Decreasing Serotonin Release in Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 263-LB
Author(s):  
XIAN ZHANG
Cell Reports ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 792-803.e4 ◽  
Author(s):  
Xian Zhang ◽  
Xin Wang ◽  
Hao Yin ◽  
Lei Zhang ◽  
Airong Feng ◽  
...  

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Xian Zhang ◽  
Xin Wang ◽  
Guo-Ping Shi ◽  
Jian Liu

Adipose tissue browning and systemic energy expenditure provide a defense mechanism against obesity and associated metabolic diseases. In western diet-fed mice, inactivation of mast cells (MCs) ameliorates obesity and insulin resistance along with improved metabolic rate. Yet, a direct role of MCs in adipose tissue thermogenesis and browning remains unclear. Here we report that, in the context of mice on a chew diet, norepinephrine (NE)-stimulated metabolic rate is increased in MC-deficient Kit w-sh/w-sh mice and MC-stabilized wide-type (WT) mice. Such functional inactivation of MCs enhances thermogenesis and browning in subcutaneous adipose tissues (SAT), but not in brown (BAT) and epididymal adipose tissues (EAT). MC reconstitution to SAT blocks the aforesaid changes in Kit w-sh/w-sh mice. Mechanistic studies demonstrate that functional inactivation of MCs not only elevates the numbers of PDGFRα + bipotential adipocyte precursors but also accelerates beige adipocyte differentiation in SAT. Using tryptophan hydroxylase 1 inhibitor, we show that MC-derived serotonin inhibits SAT beige adipocyte biogenesis and systemic energy expenditure. Together, functional inactivation of MCs or inhibition of MC serotonin synthesis in SAT promotes adipocyte browning and systemic energy metabolism in mice.


2017 ◽  
Vol 76 (6) ◽  
pp. 1142-1148 ◽  
Author(s):  
Florent Eymard ◽  
Audrey Pigenet ◽  
Danièle Citadelle ◽  
Joan Tordjman ◽  
Louise Foucher ◽  
...  

ObjectivesCompared with subcutaneous adipose tissue (SCAT), infrapatellar fat pad (IFP), the main knee intra-articular adipose tissue (IAAT), has an inflammatory phenotype in patients with osteoarthritis (OA). We phenotyped suprapatellar fat pad (SPFP) and hip acetabular fat pad (AFP), two other IAATs, to determinate the unique signature of IAATs compared with SCAT.MethodsIFP, SPFP, AFP and autologous SCAT were obtained from patients with OA during total knee (n=38) or hip replacement (n=5). Fibrosis and adipocyte area were analysed by histology and vascularisation, leucocyte and mast cell infiltration were analysed by immunohistochemistry for von Willebrand factor, leucocytes and tryptase, respectively. Secretion of interleukin (IL)-6, IL-8 and prostaglandin E2 (PGE2) was assessed by ELISA. The mRNA expression of adipocyte-associated genes (ATGL, LPL, PPAR-γ, FABP4 and CD36) and developmental genes (SFRP2, HoxC9 and EN1) was determined. The inflammatory response of isolated fibroblast-like synoviocytes (FLS) to autologous IFP and SPFP conditioned media was examined.ResultsFibrosis, vascularisation and leucocyte and mast cell infiltration were greater in IAATs than SCAT, and levels of IL-6, IL-8 and PGE2 were greater in all IAATs than SCAT. IFP and SPFP induced a similar inflammatory response to FLS. Adipocyte area was smaller in IAATs than SCAT. Adipocyte-associated and developmental genes showed a similar gene expression pattern in all IAATs, different from SCAT.ConclusionsIFP but also SPFP and AFP (gathered under the term ‘IAAT’) may play a deleterious role in OA by affecting joint homeostasis because of their inflammatory phenotype and their close interaction with synovium in the same functional unit.


2019 ◽  
Author(s):  
Frederique Van de Velde ◽  
Margriet Ouwens ◽  
Arsene-Helene Batens ◽  
Samyah Shadid ◽  
Bruno Lapauw ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 701-P
Author(s):  
PALLAVI VARSHNEY ◽  
BENJAMIN J. RYAN ◽  
CHIWOON AHN ◽  
MICHAEL W. SCHLEH ◽  
JEFFREY F. HOROWITZ

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