Abstract
All-trans-retinoic acid (atRA), an active metabolite of vitamin A, exerts a potential role in the prevention of cardiovascular diseases. It has been shown that atRA ameliorates atherosclerosis while the exact mechanism underlying this protection remains unknown. This study investigated the influence of atRA on insulin resistance (IR), atherosclerosis, and the process of perivascular adipose tissue (PVAT) browning. Moreover, syntheses of adiponectin, adipokine with anti-atherogenic effects, and tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, were determined in PVAT. Apolipoprotein E-deficient mice (Apo-E) and control C57BL/6J wild-type mice were treated with atRA (5 mg/kg/day) or vehicle (corn oil) by plastic feeding tubes for 8 weeks. Long-term atRA treatment in Apo-E mice did not affect insulin resistance. AtRa administration ameliorated atherosclerosis, induced PVAT browning, and increased adiponectin production in PVAT in Apo-E mice. Furthermore, atRA increased nitric oxide (NO) level but did not affect adiponectin concentration in the aorta of Apo-E mice. These results indicate that atRA ameliorates atherosclerosis in Apo-E mice. We also observed the browning of PVAT. Besides, atRA increased the synthesis of adiponectin in PVAT and augmented NO level in the aorta in ApoE mice.
Highlights
The perivascular adipose tissue (PVAT) has a mixed composition of both types of white (WAT) and brown adipose tissue (BAT)[1]
Body weight was higher in the vehicle and All-trans-retinoic acid (atRA)-treated Apolipoprotein E-deficient mice (Apo-E) mice when compared to C57BL/6J mice (Table 2)
There was no significant difference in HOMA-insulin resistance (IR) between the vehicletreated and the atRA-treated group of Apo-E mice, as well as between the vehicle group and the atRA group of C57BL/6J mice (Table 2)
Summary
The perivascular adipose tissue (PVAT) has a mixed composition of both types of white (WAT) and brown adipose tissue (BAT)[1]. PVAT is recognized as an active endocrine organ that secrets several adipokines playing an important role in vascular function. BAT is increasingly recognized as a potential target to reduce atherosclerosis development and has an important role in lipoprotein metabolism as thermogenesis consumes large amounts of fatty acids[14]. Experiments with the use of a mouse as a model demonstrated that activation of BAT by cold temperature enhances the clearance of plasma lipids and prevents the development of atherosclerosis[15,16]. We investigated the role of atRA in atherosclerosis and the process of PVAT browning. We explored the atRA influence on insulin resistance (IR), and pro-inflammatory and antiinflammatory adipokines synthesis in PVAT. We measured adiponectin and NO levels in the aorta of the atRA- or vehicle-treated mice
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