Obesity-related perivascular adipose tissue damage is reversed by sustained weight loss in the rat

Bussey, CE; Withers, SB; Aldous, RG; Edwards, G; Heagerty, AM

Abstract

Objective – Perivascular adipose tissue (PVAT) exerts an anticontractile effect in response to various vasoconstrictor agonists and this is lost in obesity. A recent study reported that bariatric surgery reverses the damaging effects of obesity on PVAT function. However, PVAT function has not been characterised following weight loss induced by caloric restriction, which is often the first line treatment for obesity.

Approach and Results – Contractility studies were performed using wire myography on small mesenteric arteries with and without PVAT from control, diet-induced obese, calorie restricted and sustained weight loss rats. Changes in the PVAT environment were assessed using immunohistochemistry. PVAT from healthy animals elicited an anticontractile effect in response to norepinephrine. This was abolished in diet-induced obesity through a mechanism involving increased local TNFα and reduced nitric oxide bioavailability within PVAT. Sustained weight loss led to improvement in PVAT function associated with restoration of adipocyte size, reduced TNFα and increased nitric oxide synthase function. This was associated with reversal of obesity-induced hypertension and normalisation of plasma adipokine levels, including leptin and insulin.

Conclusions – We have shown that diet-induced weight loss reverses obesity-induced PVAT damage through a mechanism involving reduced inflammation and increased nitric oxide synthase activity within PVAT. These data reveal inflammation and nitric oxide synthase, particularly eNOS, as potential targets for the treatment of PVAT dysfunction associated with obesity and the metabolic syndrome.

Citation

Bussey, C., Withers, S., Aldous, R., Edwards, G., & Heagerty, A. (2016). Obesity-related perivascular adipose tissue damage is reversed by sustained weight loss in the rat. Arteriosclerosis, Thrombosis, and Vascular Biology, 36(7), 1377-1385. https://doi.org/10.1161/ATVBAHA.116.307210

• Journal Article Type: Article
• Acceptance Date: Apr 26, 2016
• Online Publication Date: May 12, 2016
• Publication Date: Jul 1, 2016
• Deposit Date: May 20, 2016
• Publicly Available Date: Nov 12, 2016
• Journal: Arteriosclerosis, Thrombosis, and Vascular Biology
• Print ISSN: 1079-5642
• Electronic ISSN: 1524-4636
• Publisher: American Heart Association
• Volume: 36
• Issue: 7
• Pages: 1377-1385
• DOI: https://doi.org/10.1161/ATVBAHA.116.307210
• Publisher URL: http://dx.doi.org/10.1161/ATVBAHA.116.307210
• Related Public URLs: http://atvb.ahajournals.org/
• Additional Information: Projects : BHF 4 Year Studentship Scheme: Bussey, The role of perivascular adipose tissue in the control of vascular function in obesity and the potential effect of diet-induced weight loss