Journal article
Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism
Cell metabolism, Vol.24(6), pp.820-834
12/13/2016
DOI: 10.1016/j.cmet.2016.10.002
PMID: 27818258
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.
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•Cold or β-adrenergic agonists selectively reduce adipose ceramides•Adipocyte-specific inhibition of ceramide synthesis induces adipose beiging•Ceramide effects on adipose metabolism are cell autonomous•Adipose sphingolipids increase in obesity and correlate with insulin resistance
Chaurasia et al. show that whole-body and fat-specific inhibition of ceramide synthesis induces browning and increases M2 macrophages preferentially in subcutaneous WAT of obese mice. Adipose sphingolipids, increased by overnutrition and decreased by cold, modulate β-adrenergic-induced thermogenesis.
Details
- Title: Subtitle
- Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism
- Creators
- Bhagirath Chaurasia - Baker Heart and Diabetes InstituteVincent Andre Kaddai - Baker Heart and Diabetes InstituteGraeme Iain Lancaster - Baker Heart and Diabetes InstituteDarren C. Henstridge - Baker Heart and Diabetes InstituteSandhya Sriram - Singapore Bioimaging ConsortiumDwight Lark Anolin Galam - Duke-NUS Medical SchoolVenkatesh Gopalan - Singapore Bioimaging ConsortiumK.N. Bhanu Prakash - Singapore Bioimaging ConsortiumS. Sendhil Velan - Singapore Bioimaging ConsortiumSarada Bulchand - Tata Institute of Fundamental ResearchTeh Jing Tsong - Duke-NUS Medical SchoolMei Wang - Duke-NUS Medical SchoolMonowarul Mobin Siddique - Universiti Brunei DarussalamGuan Yuguang - Duke-NUS Medical SchoolKristmundur Sigmundsson - Duke-NUS Medical SchoolNatalie A. Mellet - Baker Heart and Diabetes InstituteJacquelyn M. Weir - Baker Heart and Diabetes InstitutePeter J. Meikle - Baker Heart and Diabetes InstituteM. Shabeer Bin M. Yassin - National University of SingaporeAsim Shabbir - National University of SingaporeJames A. Shayman - University of MichiganYoshio Hirabayashi - RIKEN Center for Brain ScienceSue-Anne Toh Ee Shiow - National University of SingaporeShigeki Sugii - Duke-NUS Medical SchoolScott A. Summers - Baker Heart and Diabetes Institute
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.24(6), pp.820-834
- DOI
- 10.1016/j.cmet.2016.10.002
- PMID
- 27818258
- NLM abbreviation
- Cell Metab
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Publisher
- Elsevier Inc
- Grant note
- name: Vanderbilt Mouse Metabolic Phenotyping Center, award: DK059637; DOI: 10.13039/501100000925, name: NHMRC, award: APP1112502; name: Victorian State Government OIS scheme
- Language
- English
- Date published
- 12/13/2016
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359780302771
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