Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism
| Autor: | Scott A. Summers, M. Shabeer Yassin, Venkatesh Gopalan, Yoshio Hirabayashi, Kristmundur Sigmundsson, Sarada Bulchand, S. Sendhil Velan, Jacquelyn M. Weir, Mei Wang, James A. Shayman, Teh Jing Tsong, Natalie A. Mellet, Shigeki Sugii, Dwight L. A. Galam, Asim Shabbir, Peter J. Meikle, Monowarul Mobin Siddique, K. N. Bhanu Prakash, Sue Anne Toh Ee Shiow, Bhagirath Chaurasia, Sandhya Sriram, Graeme I. Lancaster, Vincent A. Kaddai, Guan Yuguang, Darren C. Henstridge |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
FGF21 Physiology Serine C-Palmitoyltransferase Adipose tissue White adipose tissue Body Mass Index chemistry.chemical_compound Mice 0302 clinical medicine Adipose Tissue Brown Adipocyte Adipocytes Cell Differentiation Thermogenesis Adrenergic beta-Agonists Middle Aged Cold Temperature Organ Specificity 030220 oncology & carcinogenesis Adult medicine.medical_specialty Adipose tissue macrophages Subcutaneous Fat Adipokine Dioxoles Carbohydrate metabolism Biology Ceramides 03 medical and health sciences Young Adult Internal medicine medicine Diabetes Mellitus Animals Humans Obesity Molecular Biology Aged Inflammation Sphingolipids 3T3-L1 Cell Biology Fatty Liver 030104 developmental biology Endocrinology Glucose chemistry Gene Expression Regulation Energy Metabolism Gene Deletion |
| Zdroj: | Cell metabolism. 24(6) |
| ISSN: | 1932-7420 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|