Abstract 12058: Bariatric Surgery Reduces Adipose Inflammation and Improves Vascular Function in Type 2 Diabetic Mice
Bariatric surgery (BS) is emerging as an effective method to alleviate a multitude of conditions associated with morbid obesity and type 2 diabetes. However, little is known about the effects and mechanisms of BS on visceral adipose inflammation and vascular dysfunction in type 2 diabetes. Our previous study revealed the crucial role of interferon-gamma (IFN) in the regulation of visceral adipose inflammation and vascular dysfunction in type 2 diabetes. Within this context, we assess the hypothesis that BS-induced reduction of IFN-mediated adipose inflammation contributes to the improvement of vascular function in type 2 diabetic mice (Leprdb). To test this hypothesis, control mice (m Leprdb) and Leprdb mice were treated with either sham or BS and then evaluated at 5, 10, 20, and 30 days to assess post-surgical effects. BS was found to reduce body weight, fat mass, abdominal girth, mesenteric bed weight, and fasting glucose level in Leprdb without affecting those parameters in m Leprdb (n=6∼8 mice). The decrease in visceral adiposity is accompanied by amelioration of T-lymphocytes and macrophage infiltration, as well as reduction in mRNA and protein expression of IFN and monocyte chemoattractant protein-1 (MCP-1) in the mesenteric adipose (MAT) of Leprdb mice after BS. Furthermore, BS improves endothelial-dependent vasorelaxation to acetylcholine without affecting endothelial-independent vasorelaxation to sodium nitroprusside in small mesenteric arteries (SMA) of Leprdb mice. The improvement in endothelial function was abolished with nitric oxide synthase inhibitor (L-NAME) incubation, supporting the view that BS effectively improving vascular NO production in Leprdb. Superoxide production in MAT/SMA and macrophage accumulation in the vessel wall of SMA are elevated in diabetic mice. BS and anti-IFN treatment reduced MAT/SMA oxidative stress in Leprdb mice. Anti-IFN reduced macrophages accumulation in SMA of Leprdb, while IFN showed the opposite effects in m Leprdb. In conclusion, BS ameliorates adipose inflammation and vascular dysfunction in type 2 diabetes though inhibiting IFN-mediated adipose/vascular oxidative stress and inflammation in addition to reducing body weight and improving glycemic control.
- © 2010 by American Heart Association, Inc.