Intra‐Abdominal Lipectomy Reduces Large Arterial Stiffness and Blood Pressure in Metabolic Syndrome

Abstract

Increased intra‐abdominal (visceral) adipose tissue is a key feature of the metabolic syndrome. Expansion of visceral adipose tissue and the associated altered adipokine profile are linked to the development of hypertension. While reduction in visceral adipose tissue volume offers cardioprotective effects, the mechanisms underlying these effects remain understudied and unclear. In this study, we removed ~90% of visceral adipose tissue (=~5% body weight) by intra‐abdominal lipectomy and assessed large arterial stiffness, large artery structural matrix components, and blood pressure in a metabolic syndrome rat model (JCR:LA‐cp, JCR). Large artery compliance was significantly decreased in JCR vs. normal (Sprague Dawley, SD) rats (75±2% JCR vs. SD (carotid)) with a concomitant significant increase in MMP12‐dependent elastin degradation (3–6 fold vs. SD). Intra‐abdominal lipectomy normalized large artery stiffness, blocked MMP12 activation and reduced elastin degradation in JCR animals (~75% (carotid) vs. untreated JCR). Likewise, hypertension in JCR animals was significantly attenuated by intra‐abdominal lipectomy (MABP=156±3 mmHg JCR vs. 90±6 mmHg SD vs. 132±4 mmHg JCR+lipectomy). 20‐hydroxyeicosatetraeonic acid (20‐HETE), an arachidonic acid metabolite known to be a potent vasoconstrictor in resistance arteries, was significantly elevated in the visceral adipose tissue of JCR rats (~6 fold vs. SD). Like intra‐abdominal lipectomy, 20‐HETE antagonists restored large artery elasticity, blocked MMP12 activation and elastin degradation and significantly decreased blood pressure (125±3 mmHg JCR+20‐HETE antagonists) in JCR rats. Thus, 20‐HETE may be an important adipokine that mediates, in part, the adverse effects of expanded visceral fat volume in the metabolic syndrome. Its removal and inhibition may provide therapeutic and pharmacological approaches, respectively, for the management of central obesity‐driven large artery stiffness and hypertension in the metabolic syndrome.Support or Funding InformationNational Heart, Lung and Blood Institute (NHLBI): 1F31HL137356‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.