title: Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.
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.
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Dionne E
authors.initials: DE
authors.lastname: Maessen
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Olaf
authors.initials: O
authors.lastname: Brouwers
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Katrien H
authors.initials: KH
authors.lastname: Gaens
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Wouters
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Pathology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Jack P
authors.initials: JP
authors.lastname: Cleutjens
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Pharmacology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Janssen
authors.affiliation: United Centers for Advanced Research and Translational Medicine, Tohoku University, Sendai, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyata
authors.affiliation: CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: 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.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004334:Drug Administration Schedule; D040181:Genetic Diseases, X-Linked / Q000378:metabolism / Q000473:pathology; D005877:Gigantism / Q000378:metabolism / Q000473:pathology; D006330:Heart Defects, Congenital / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D007333:Insulin Resistance; D008607:Intellectual Disability / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D015434:Panniculitis / Q000378:metabolism / Q000517:prevention & control*; D011733:Pyridoxamine / Q000008:administration & dosage*; D061665:Time-to-Treatment
chemical_list: D011733:Pyridoxamine