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In Vivo Administration of an EET Agonist Rescues Diet‐ Induced Obesity and Associated Vascular and Adipose Tissue Abnormalities in SD Rats: Contributions of the Heme‐Heme Oxygenase System
Author(s) -
Sodhi Komal,
Inoue Kazuyoshi,
Schwartzman Michal L
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.819.51
Subject(s) - medicine , adipose tissue , endocrinology , adiponectin , heme oxygenase , enos , agonist , chemistry , heme , obesity , nitric oxide , receptor , insulin resistance , nitric oxide synthase , biochemistry , enzyme
Recent reports show interplay between EETs and the heme oxygenase (HO) system in attenuating adipogenesis in in vitro models, prompting an examination of the effects of treatment with an EET agonist on diet‐induced obesity and associated cardio‐metabolic dysfunction. Patho‐physiological effects of an EET agonist (NUDSA) were contrasted, in the absence and in the presence of SnMP (an HO inhibitor), in SD rats fed a high fat (58%, HF) or lean diet for 16 weeks. HF diet resulted in increased (p<0.05) body weight (BW), inflammatory cytokines and decreased levels adiponectin in the plasma; along with reduced vascular and adipose tissue levels of EETs and HO‐1. Treatment with NUDSA not only reversed BW, serum adiponectin and vascular and adipose tissue levels of EETs and HO‐1, but also, decreased blood pressure, subcutaneous and visceral fat content and serum TNFα and IL‐6 in rats on HF diet. Aortic endothelial function, p‐eNOS expression and adipose tissue markers of energy homeostasis i.e. pAMPK, Sirt1 and FAS, impaired (p<0.05) in rats on HF diet, were restored in animals treated with NUDSA. Prevention of these beneficial effects of NUDSA, in animals on HF diet and concurrently exposed to NUDSA and SnMP, support the role of EET‐HO interaction in mediating such effects. Taken together, our findings suggest that interplay of these two systems affords vascular and metabolic protection in diet induced obesity. NIH‐ HL034300