Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet–Induced Obese Mice
| Autor: | Ben J. A. Janssen, Coen D.A. Stehouwer, Olaf Brouwers, Katrien H.J. Gaens, Kristiaan Wouters, Casper G. Schalkwijk, Toshio Miyata, Jack P.M. Cleutjens, Dionne E. Maessen |
|---|---|
| Přispěvatelé: | Promovendi CD, Interne Geneeskunde, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Pathologie, RS: CARIM - R3.06 - The vulnerable plaque: makers and markers, Farmacologie en Toxicologie, RS: CARIM - R2.03 - ECM + Wnt signaling, MUMC+: MA Interne Geneeskunde (3) |
| Rok vydání: | 2015 |
| Předmět: |
Heart Defects
Congenital Male 0301 basic medicine medicine.medical_specialty Panniculitis Endocrinology Diabetes and Metabolism Mice Obese Adipose tissue 030209 endocrinology & metabolism Inflammation Type 2 diabetes Biology Carbohydrate metabolism Diet High-Fat Drug Administration Schedule Gigantism Time-to-Treatment Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Insulin resistance 3T3-L1 Cells Intellectual Disability Internal medicine Internal Medicine medicine Animals Humans Obesity Cells Cultured Arrhythmias Cardiac Genetic Diseases X-Linked medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology Adipose Tissue Adipogenesis Insulin Resistance Adipocyte hypertrophy medicine.symptom Pyridoxamine |
| Zdroj: | Diabetes, 65(4), 956-966. American Diabetes Association |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db15-1390 |
| Popis: | Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)–induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by PM supplementation. PM inhibited the expansion of adipose tissue and adipocyte hypertrophy in mice. In addition, adipogenesis of murine 3T3-L1 and human Simpson-Golabi-Behmel Syndrome preadipocytes was dose- and time-dependently reduced by PM, as demonstrated by Oil Red O staining and reduced expression of adipogenic differentiation genes. No ectopic fat deposition was found in the liver of HFD mice. The high expression of proinflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. Treatment with PM partially prevented HFD-induced mild vascular dysfunction. Altogether, these findings highlight the potential of PM to serve as an intervention strategy in obesity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|