Perivascular fatty tissue at the brachial artery is linked to insulin resistance but not to local endothelial dysfunction

Department of Endocrinology, University of Tübingen, Otfried-Müller Strasse 10, 72076, Tübingen, Germany.
Diabetologia (Impact Factor: 6.67). 09/2008; 51(11):2093-9. DOI: 10.1007/s00125-008-1128-3
Source: PubMed


Different ectopic fat depots, such as visceral or hepatic fat, are known to affect whole body insulin sensitivity. It has recently been hypothesised that differences in perivascular adipose tissue (PVAT) mass around resistance vessels may also contribute to insulin resistance, possibly via direct vascular effects leading to reduced capillary cross-sectional area in the muscle, which in turn affects muscular blood flow and glucose uptake. Based on this, the aim of the present study was to test whether PVAT around conduit arteries (i.e. the brachial artery) influences NO bioavailability, expressed as flow-mediated dilation (FMD), or insulin sensitivity in humans in vivo.
Insulin sensitivity was measured by OGTT in all 95 participants (59 women, 36 men; median age 47 years, range 19-66 years) and by the gold standard, a euglycaemic-hyperinsulinaemic clamp, in a randomly selected subgroup of 33 participants. Quantification of the different fat compartments, including PVAT around the brachial artery, was achieved by high-resolution magnetic resonance imaging (1.5 T). Blood flow and FMD were measured at the brachial artery using high-resolution (13 MHz) ultrasound, after 5 min of forearm occlusion.
PVAT was negatively correlated with insulin sensitivity and the post-ischaemic increase in blood flow. The association between PVAT and insulin sensitivity (r = -0.54, beta = -0.37, p = 0.009) was independent of age, sex, visceral adipose tissue, liver fat, BMI and further cardiovascular risk factors. No correlation could be detected between PVAT and local endothelial function. However, we observed an independent association between PVAT and post-ischaemic increase in blood flow (r = -0.241; beta = -1.69; p = 0.02).
PVAT seems to play an independent role in the pathogenesis of insulin resistance. This may be due to direct vascular effects influencing muscular blood flow.

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Available from: Michael Boettcher, Oct 06, 2015
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    • "In a study using multidetector CT, abdominal periaortic adipose tissue was defined by a 5-mm cylindrical region of interest around the aortic wall [19]. Additionally, high-resolution MRI can quantify perivascular fat around arteries [20]. "
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    ABSTRACT: It is well known that people with high levels of body fat are at higher risk for developing diabetes mellitus, kidney disease, and cardiovascular disorders. Since individuals who are slightly overweight, or even individuals of normal weight, can vary in body fat distribution, their metabolic profiles and the degree of association of these profiles with cardiometabolic risk factors may differ. Fat distribution might be more of a predictive factor for cardiorenometabolic risk than obesity itself, which has led researchers to investigate whether ectopic fat accumulation may partially account for the development of cardiorenometabolic disorders. In addition to visceral obesity, fat can accumulate in the liver and muscle, and these intrahepatic and intramuscular lipid stores are associated with insulin resistance and adverse metabolic phenotypes. More recently, pericardial fat, perivascular fat, and perirenal fat were found to be associated with coronary atherosclerosis, cardiovascular diseases, and kidney damage, respectively. Thus, regional fat distribution may play a key role in understanding the development of cardiorenometabolic diseases in nonobese people.
    03/2014; 29(1):1-4. DOI:10.3803/EnM.2014.29.1.1
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    • "It also does not appear to be a species effect, as similar results were observed in rat, mouse, dog, pig, and human vessels. This occurs in various vascular beds, like the aorta, the mesenteric circulation, coronary arteries,53 or limb vessels,54 therefore suggesting it does not depend either on the white- or the brown-like quality of the adipose tissue. The anticontractile effect of PVAT was also reproduced for veins,55 which like arteries, are surrounded by PVAT. "
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    ABSTRACT: The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT.
    Vascular Health and Risk Management 03/2013; 9:105-16. DOI:10.2147/VHRM.S33760
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    • "PVAT may have a direct paracrine, and possibly vasocrine (i.e., from one vessel to downstream vessels), effect on the vasculature due to the inherent proximity to the vasculature (9,20). In humans, PVAT around the brachial artery is independently associated with insulin sensitivity (21). Additionally, PVAT exhibits an altered adipokine profile compared with other adipose depots in obesity (10,11,22). "
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    ABSTRACT: Microvascular recruitment in muscle is a determinant of insulin sensitivity. Whether perivascular adipose tissue (PVAT) is involved in disturbed insulin-induced vasoreactivity is unknown, as are the underlying mechanisms. This study investigates whether PVAT regulates insulin-induced vasodilation in muscle, the underlying mechanisms, and how obesity disturbs this vasodilation. Insulin-induced vasoreactivity of resistance arteries was studied with PVAT from C57BL/6 or db/db mice. PVAT weight in muscle was higher in db/db mice compared with C57BL/6 mice. PVAT from C57BL/6 mice uncovered insulin-induced vasodilation; this vasodilation was abrogated with PVAT from db/db mice. Blocking adiponectin abolished the vasodilator effect of insulin in the presence of C57BL/6 PVAT, and adiponectin secretion was lower in db/db PVAT. To investigate this interaction further, resistance arteries of AMPKα2(+/+) and AMPKα2(-/-) were studied. In AMPKα2(-/-) resistance arteries, insulin caused vasoconstriction in the presence of PVAT, and AMPKα2(+/+) resistance arteries showed a neutral response. On the other hand, inhibition of the inflammatory kinase Jun NH(2)-terminal kinase (JNK) in db/db PVAT restored insulin-induced vasodilation in an adiponectin-dependent manner. In conclusion, PVAT controls insulin-induced vasoreactivity in the muscle microcirculation through secretion of adiponectin and subsequent AMPKα2 signaling. PVAT from obese mice inhibits insulin-induced vasodilation, which can be restored by inhibition of JNK.
    Diabetes 10/2012; 62(2). DOI:10.2337/db11-1603 · 8.10 Impact Factor
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