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Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism. 2016
Bhagirath Chaurasia, and
Vincent Andre Kaddai, and
Graeme Iain Lancaster, and
Darren C Henstridge, and
Sandhya Sriram, and
Dwight Lark Anolin Galam, and
Venkatesh Gopalan, and
K N Bhanu Prakash, and
S Sendhil Velan, and
Sarada Bulchand, and
Teh Jing Tsong, and
Mei Wang, and
Monowarul Mobin Siddique, and
Guan Yuguang, and
Kristmundur Sigmundsson, and
Natalie A Mellet, and
Jacquelyn M Weir, and
Peter J Meikle, and
M Shabeer Bin M Yassin, and
Asim Shabbir, and
James A Shayman, and
Yoshio Hirabayashi, and
Sue-Anne Toh Ee Shiow, and
Shigeki Sugii, and
Scott A Summers
Laboratory of Translational Metabolic Health, Baker IDI Heart and Diabetes Institute, Melbourne 3004, Australia. Electronic address: bhagirath.chaurasia@health.utah.edu.
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.
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