Bariatric Surgery Reduces Visceral Adipose Inflammation and Improves Endothelial Function in Type 2 Diabetic Mice

Abstract

Objective 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. Conclusions The amelioration of adipose tissue inflammation and the improvement of endothelial function may represent important mechanisms that result in cardiovascular benefits following bariatric surgery.

Inflammatory markers and bariatric surgery: a meta-analysis

“…TNFa was found to impair endothelial function, and endothelial dependent vasorelaxation improved after surgery in these animals. Surgery was also found to improve oxidative stress in the mesenteric adipose tissue in Lepr db mice [116].…”

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

“…Recovery from metabolic disease is associated with decreased inflammation, both systemic and in adipose tissue (17,37,52,55,57,58,67,78). Insulin-independent reversal of T1D following BAT transplants follows a similar pattern, resulting in a progressive decrease in inflammation both systemically and in adipose tissue (26 -28).…”

Role of Adiposity-Driven Inflammation in Depressive Morbidity

“…One of the main protagonists is the white adipose tissue, as shown by findings reporting associations between circulating levels of cytokines and measures of central adiposity (Park et al, 2005;Visser et al, 1999). Conversely, weight loss, induced either by low-caloric diet or bariatric surgery, significantly reduces peripheral inflammation in obese individuals (Belza et al, 2009;Hakeam et al, 2009;Manco et al, 2007;Rao, 2012) and animals (Liu et al, 2014;Schneck et al, 2014;Zhang et al, 2011). Adipocytes, together with infiltrated macrophages and T cells that progressively accumulate in the white adipose tissue, have indeed the ability to potently secrete inflammatory mediators (Cancello et al, 2006;Gregor and Hotamisligil, 2011;Kim et al, 2014;Lasselin et al, 2014b;Zeyda et al, 2011).…”