Bariatric surgery is emerging as an effective method to alleviate a multitude of medical conditions associated with morbid obesity and type 2 diabetes. However, little is known about the effects and mechanisms of bariatric surgery on visceral fat inflammation and endothelial dysfunction in type 2 diabetes. We hypothesize that bariatric surgery ameliorates interferon-gamma (IFNγ-mediated adipose tissue inflammation/oxidative stress and improves endothelial function in type 2 diabetic mice.
Methods and Results
Control mice (m Leprdb) and diabetic mice (Leprdb) were treated with either sham surgery or Improved Gastric Bypass Surgery (IGBS) and then evaluated at 5, 10, 20, and 30 days to assess post-surgical effects. Surgery reduced body weight, abdominal adiposity, blood glucose level, and food intake in Leprdb. The surgery-induced decrease in visceral adiposity was accompanied by amelioration of T-lymphocytes and macrophage infiltration, as well as reduction in the expression of IFNγ and other inflammatory cytokines in the mesenteric adipose tissue (MAT) of Leprdb mice. Furthermore, surgery improved endothelium-dependent, but not endothelium-independent vasorelaxation in small mesenteric arteries (SMA) of Leprdb mice. The improvement in endothelial function was largely attenuated by nitric oxide synthase inhibitor (L-NAME) incubation. IFNγ treatment increased the mRNA expression of tumor necrosis factor-alpha (TNFα) in the MAT of control mice, and incubation of SMA of control mice with TNFα caused impairment of endothelial function. Superoxide production in MAT/SMA and nitrotyrosine protein level in SMA were elevated in diabetic mice. Surgery reduced MAT/SMA oxidative stress in Leprdb mice.
The amelioration of adipose tissue inflammation and the improvement of endothelial function may represent important mechanisms that result in cardiovascular benefits following bariatric surgery.
Keywords: Diabetes, Adipose, Inflammation, Endothelial Function, Interferon-gamma