Format

Send to

Choose Destination
Diabetes. 2016 Apr;65(4):956-66. doi: 10.2337/db15-1390. Epub 2015 Dec 30.

Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

Author information

1
CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
2
CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Pathology, Maastricht University Medical Center, Maastricht, the Netherlands.
3
CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Pharmacology, Maastricht University Medical Center, Maastricht, the Netherlands.
4
United Centers for Advanced Research and Translational Medicine, Tohoku University, Sendai, Japan.
5
CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands c.schalkwijk@maastrichtuniversity.nl.

Abstract

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.

PMID:
26718500
DOI:
10.2337/db15-1390
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center