Back to Search
Start Over
Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism.
- Source :
-
Cell metabolism [Cell Metab] 2016 Dec 13; Vol. 24 (6), pp. 820-834. Date of Electronic Publication: 2016 Nov 03. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Adipocytes drug effects
Adipose Tissue, Brown drug effects
Adrenergic beta-Agonists pharmacology
Adult
Aged
Animals
Body Mass Index
Cell Differentiation drug effects
Cell Differentiation genetics
Cold Temperature
Diabetes Mellitus metabolism
Dioxoles pharmacology
Energy Metabolism drug effects
Fatty Liver metabolism
Fatty Liver pathology
Gene Deletion
Gene Expression Regulation drug effects
Glucose metabolism
Humans
Inflammation genetics
Mice
Middle Aged
Obesity metabolism
Obesity pathology
Organ Specificity drug effects
Serine C-Palmitoyltransferase metabolism
Sphingolipids biosynthesis
Sphingolipids metabolism
Subcutaneous Fat drug effects
Subcutaneous Fat metabolism
Thermogenesis drug effects
Thermogenesis genetics
Young Adult
Adipocytes metabolism
Adipose Tissue, Brown metabolism
Adipose Tissue, Brown pathology
Ceramides pharmacology
Inflammation pathology
Subcutaneous Fat pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-7420
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 27818258
- Full Text :
- https://doi.org/10.1016/j.cmet.2016.10.002