Targeting sphingolipid metabolism in the treatment of obesity/type 2 diabetes.
Expert Opin Ther Targets
; 19(8): 1037-50, 2015.
Article
em En
| MEDLINE
| ID: mdl-25814122
ABSTRACT
INTRODUCTION:
Obesity is a major factor that is linked to the development of type 2 diabetes (T2D). Excess circulating fatty acids (FAs), which characterize obesity, induce insulin resistance, steatosis, ß cells dysfunction and apoptosis. These deleterious effects have been defined as lipotoxicity. AREAS COVERED FAs are metabolized to different lipid species, including ceramides which play a crucial role in lipotoxicity. The action of ceramides on tissues, such as muscle, liver, adipose tissue and pancreatic ß cells, during the development of T2D will also be reviewed. In addition, the potential antagonist action of other sphingolipids, namely sphingoid base phosphates, on lipotoxicity in skeletal muscle and ß cells will be addressed. EXPERT OPINION Ceramide is a critical mediator to the development of T2D linked to obesity. Targeting proteins involved in ceramide's deleterious action has not been possible due to their involvement in many other intracellular signaling pathways. A possible means of counteracting ceramide action would be to prevent the accumulation of the specific ceramide species involved in both insulin resistance and ß-cell apoptosis/dysfunction. Another possibility would be to adjust the dynamic balance between ceramide and sphingoid base phosphate, both known to display opposing properties on the development of T2D-linked obesity.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esfingolipídeos
/
Diabetes Mellitus Tipo 2
/
Obesidade
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article