Perivascular Adipose Tissue and Its Role in Type 2 Diabetes and Cardiovascular Disease

Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. Adipose tissue-derived substances (adipokines) and especially inflammatory products of adipose tissue control insulin sensitivity and vascular function. In the past years, adipose tissue associated with the vasculature, or perivascular adipose tissue (PAT), has been shown to produce a variety of adipokines that contribute to regulation of vascular tone and local inflammation. This review describes our current understanding of the mechanisms linking perivascular adipose tissue to vascular function, inflammation, and insulin resistance. Furthermore, we will discuss mechanisms controlling the quantity and adipokines secretion by PAT

Perivascular Fat and the Microcirculation: Relevance to Insulin Resistance, Diabetes, and Cardiovascular Disease

Type 2 diabetes and its major risk factor, obesity, are a growing burden for public health. The mechanisms that connect obesity and its related disorders, such as insulin resistance, type 2 diabetes, and hypertension, are still undefined. Microvascular dysfunction may be a pathophysiologic link between insulin resistance and hypertension in obesity. Many studies have shown that adipose tissue-derived substances (adipokines) interact with (micro)vascular function and influence insulin sensitivity. In the past, research focused on adipokines from perivascular adipose tissue (PVAT). In this review, we focus on the interactions between adipokines, predominantly from PVAT, and microvascular function in relation to the development of insulin resistance, diabetes, and cardiovascular disease

Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin

OBJECTIVE: A major site of action for the atheroprotective drug nicotinic acid (NA) is adipose tissue, via the G-protein-coupled receptor, GPR109A. Since, adipose tissue is an active secretory organ that contributes both positively and negatively to systemic inflammatory processes associated with cardiovascular disease, we hypothesized that NA would act directly upon adipocytes to alter the expression of pro-inflammatory chemokines, and the anti-inflammatory adipokine adiponectin. METHODS AND RESULTS: TNF-alpha treatment (1.0ng/mL) of 3T3-L1 adipocytes resulted in an increase in gene expression of fractalkine (9+/-3.3-fold, P<0.01); monocyte chemoattractant protein-1 (MCP-1) (24+/-1.2-fold, P<0.001), 'regulated upon activation, normal T cell expressed and secreted' (RANTES) (500+/-55-fold, P<0.001) and inducible nitric oxide synthase (iNOS) (200+/-70-fold, P<0.05). The addition of NA (10(-4)M) to TNF-alpha-treated adipocytes attenuated expression of fractalkine (50+/-12%, P<0.01); MCP-1 (50+/-6%, P<0.01), RANTES (70+/-3%, P<0.01) and iNOS (60+/-16%). This pattern was mirrored in protein released from the adipocytes into the surrounding media. The effect on gene expression was neutralised by pre-treatment with pertussis toxin. NA attenuated macrophage chemotaxis (by 27+/-3.5%, P<0.001) towards adipocyte conditioned media. By contrast, NA, (10(-6)-10(-3)M) increased, in a dose-dependent manner, mRNA of the atheroprotective hormone adiponectin (3-5-fold n=6, P<0.01). CONCLUSIONS: NA suppresses pro-atherogenic chemokines and upregulates the atheroprotective adiponectin through a G-protein-coupled pathway. Since adipose tissue has the potential to contribute to both systemic and local (perivascular) inflammation associated with atherosclerosis our results suggest a new "pleiotropic" role for NA

The association of visceral adiposity with cardiovascular events in patients with peripheral artery disease

Background: Previous studies have suggested that patients with peripheral artery disease (PAD) suffer from a high incidence of cardiovascular events (CVE). Visceral adiposity has been implicated in promoting CVEs. This study aimed to assess the association of relative visceral adipose volume with incident cardiovascular events in patients with peripheral artery disease. Methods: This was a prospective cohort study including 260 patients with PAD who presented between 2003 and 2012. Cases were patients with diagnosed PAD including symptomatic lower limb athero-thrombosis and asymptomatic abdominal aortic aneurysm. All patients underwent computed tomography angiography (CTA). Abdominal visceral to total adipose volume ratio (relative visceral adipose volume) was estimated from CTAs using a previously validated workstation protocol. Cardiovascular risk factors were recorded at entry. The association of visceral adiposity with major CVEs (death, non-fatal myocardial infarction or stroke) was examined using Kaplan Meier and Cox proportional hazard analyses. Results: A total of 92 major CVEs were recorded in 76 patients during a median follow-up of 2.8 (IQR 1.2 to 4.8) years, including myocardial infarction (n = 26), stroke (n = 10) and death (n = 56). At 3 years the incidence of major CVEs stratified by relative visceral adipose volume quartiles were 15% [Quartile (Q) 1], 17% (Q2), 11% (Q3) and 15% (Q4) (P = 0.517). Relative visceral adipose volume was not associated with major CVEs after adjustment for other risk factors. Conclusion: This study suggests that visceral adiposity does not play a central role in the predisposition for major CVEs in patients with PAD