Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism

Bhagirath Chaurasia, Vincent Andre Kaddai, Graeme Iain Lancaster, Darren C. Henstridge, Sandhya Sriram, Dwight Lark Anolin Galam, Venkatesh Gopalan, K.N.Bhanu Prakash, S. Sendhil Velan, Sarada Bulchand, Teh Jing Tsong, Mei Wang, Monowarul Mobin Siddique, Guan Yuguang, Kristmundur Sigmundsson, Natalie A. Mellet, Jacquelyn M. Weir, Peter J. Meikle, M. Shabeer Bin M. Yassin, Asim ShabbirJames A. Shayman, Yoshio Hirabayashi, Sue-Anne Toh Ee Shiow, Shigeki Sugii, Scott A. Summers

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Abstract

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.

Original languageEnglish
Pages (from-to)820-834
Number of pages15
JournalCell Metabolism
Volume24
Issue number6
DOIs
Publication statusPublished - 13 Dec 2016
Externally publishedYes

Cite this

Chaurasia, B., Kaddai, V. A., Lancaster, G. I., Henstridge, D. C., Sriram, S., Galam, D. L. A., Gopalan, V., Prakash, K. N. B., Velan, S. S., Bulchand, S., Tsong, T. J., Wang, M., Siddique, M. M., Yuguang, G., Sigmundsson, K., Mellet, N. A., Weir, J. M., Meikle, P. J., Bin M. Yassin, M. S., ... Summers, S. A. (2016). Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism. Cell Metabolism, 24(6), 820-834. https://doi.org/10.1016/j.cmet.2016.10.002