Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism

被引：222

作者：

Chaurasia, Bhagirath ^{[1
,14
]}

Kaddai, Vincent Andre ^{[1
]}

Lancaster, Graeme Iain ^{[1
]}

Henstridge, Darren C. ^{[2
]}

Sriram, Sandhya ^{[3
]}

Galam, Dwight Lark Anolin ^{[4
]}

Gopalan, Venkatesh ^{[5
]}

Prakash, K. N. Bhanu ^{[5
]}

Velan, S. Sendhil ^{[5
]}

Bulchand, Sarada ^{[6
]}

Tsong, Teh Jing ^{[7
]}

Wang, Mei ^{[7
]}

Siddique, Monowarul Mobin ^{[8
]}

Guan Yuguang ^{[4
]}

Sigmundsson, Kristmundur ^{[4
]}

Mellet, Natalie A. ^{[9
]}

Weir, Jacquelyn M. ^{[9
]}

Meikle, Peter J. ^{[9
]}

Yassin, M. Shabeer Bin M. ^{[10
]}

Shabbir, Asim ^{[11
]}

Shayman, James A. ^{[12
]}

Hirabayashi, Yoshio ^{[13
]}

Shiow, Sue-Anne Toh Ee

Sugii, Shigeki ^{[3
,4
]}

Summers, Scott A. ^{[1
,14
]}

机构：

[1] Baker IDI Heart & Diabet Inst, Lab Translat Metab Hlth, Melbourne, Vic 3004, Australia

[2] Baker IDI Heart & Diabet Inst, Cellular & Mol Metab Lab, Melbourne, Vic 3004, Australia

[3] Singapore Bioimaging Consortium, Fat Metab & Stem Cell Grp, Singapore 138667, Singapore

[4] Duke NUS Grad Med Sch, Program Cardiovasc & Metab Disorders, Singapore 169547, Singapore

[5] Singapore Bioimaging Consortium, Lab Mol Imaging, Singapore 138667, Singapore

[6] Tata Inst Fundamental Res, Mumbai 400005, Maharashtra, India

[7] Duke NUS Grad Med Sch, Program Canc & Stem Cell Biol, Singapore 169857, Singapore

[8] Univ Brunei Darussalam, Fac Sci, Gadong 1410, Brunei

[9] Baker IDI Heart & Diabet Inst, Metab Lab, Melbourne, Vic 3004, Australia

[10] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117599, Singapore

[11] Natl Univ Singapore, Dept Surg, Singapore 117599, Singapore

[12] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[13] RIKEN Brain Sci Inst, Wako, Saitama 3510198, Japan

[14] Univ Utah, Dept Nutr & Integrat Physiol, Salt Lake City, UT 84112 USA

来源：

Cell Metabolism | 2016年 / 24卷 / 06期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

INDUCED INSULIN-RESISTANCE; STEM-CELLS; OBESITY; TISSUE; INHIBITION; IDENTIFICATION; BIOSYNTHESIS; LIPOTOXICITY; MACROPHAGES; EXPRESSION;

D O I：

10.1016/j.cmet.2016.10.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 insulinsensitizing 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.

引用

页码：820 / 834

页数：15

共 35 条

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Lipid oversupply, selective insulin resistance, and lipotoxicity: Molecular mechanisms [J].