TY - JOUR
T1 - Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism
AU - Chaurasia, Bhagirath
AU - Kaddai, Vincent Andre
AU - Lancaster, Graeme Iain
AU - Henstridge, Darren C.
AU - Sriram, Sandhya
AU - Galam, Dwight Lark Anolin
AU - Gopalan, Venkatesh
AU - Prakash, K.N.Bhanu
AU - Velan, S. Sendhil
AU - Bulchand, Sarada
AU - Tsong, Teh Jing
AU - Wang, Mei
AU - Siddique, Monowarul Mobin
AU - Yuguang, Guan
AU - Sigmundsson, Kristmundur
AU - Mellet, Natalie A.
AU - Weir, Jacquelyn M.
AU - Meikle, Peter J.
AU - Bin M. Yassin, M. Shabeer
AU - Shabbir, Asim
AU - Shayman, James A.
AU - Hirabayashi, Yoshio
AU - Shiow, Sue-Anne Toh Ee
AU - Sugii, Shigeki
AU - Summers, Scott A.
PY - 2016/12/13
Y1 - 2016/12/13
N2 - Adipocytes package incoming fatty acids into triglycerides and other glycerolipids, with only a fraction spilling into a parallel biosynthetic pathway that produces sphingolipids. Herein, we demonstrate that subcutaneous adipose tissue of type 2 diabetics contains considerably more sphingolipids than non-diabetic, BMI-matched counterparts. Whole-body and adipose tissue-specific inhibition/deletion of serine palmitoyltransferase (Sptlc), the first enzyme in the sphingolipid biosynthesis cascade, in mice markedly altered adipose morphology and metabolism, particularly in subcutaneous adipose tissue. The reduction in adipose sphingolipids increased brown and beige/brite adipocyte numbers, mitochondrial activity, and insulin sensitivity. The manipulation also increased numbers of anti-inflammatory M2 macrophages in the adipose bed and induced secretion of insulin-sensitizing adipokines. By comparison, deletion of serine palmitoyltransferase from macrophages had no discernible effects on metabolic homeostasis or adipose function. These data indicate that newly synthesized adipocyte sphingolipids are nutrient signals that drive changes in the adipose phenotype to influence whole-body energy expenditure and nutrient metabolism.
AB - Adipocytes package incoming fatty acids into triglycerides and other glycerolipids, with only a fraction spilling into a parallel biosynthetic pathway that produces sphingolipids. Herein, we demonstrate that subcutaneous adipose tissue of type 2 diabetics contains considerably more sphingolipids than non-diabetic, BMI-matched counterparts. Whole-body and adipose tissue-specific inhibition/deletion of serine palmitoyltransferase (Sptlc), the first enzyme in the sphingolipid biosynthesis cascade, in mice markedly altered adipose morphology and metabolism, particularly in subcutaneous adipose tissue. The reduction in adipose sphingolipids increased brown and beige/brite adipocyte numbers, mitochondrial activity, and insulin sensitivity. The manipulation also increased numbers of anti-inflammatory M2 macrophages in the adipose bed and induced secretion of insulin-sensitizing adipokines. By comparison, deletion of serine palmitoyltransferase from macrophages had no discernible effects on metabolic homeostasis or adipose function. These data indicate that newly synthesized adipocyte sphingolipids are nutrient signals that drive changes in the adipose phenotype to influence whole-body energy expenditure and nutrient metabolism.
UR - http://www.scopus.com/inward/record.url?scp=85003837216&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2016.10.002
DO - 10.1016/j.cmet.2016.10.002
M3 - Article
C2 - 27818258
AN - SCOPUS:85003837216
VL - 24
SP - 820
EP - 834
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -
