Abstract P220: Abdominal Aortic Perivascular Adipose Tissue Lipolysis Is Activated In Hypertensive Dahl SS Rats Fed a High-Fat Diet

Abstract

Perivascular adipose tissues (PVAT) possess anti-contractile functions that are lost during hypertension (HTN). PVAT stores fatty acids (FA) and releases them through lipolysis upon adrenergic or inflammatory stimuli. Visceral AT lipolysis in humans with high abdominal adiposity and hypertension elevates FA release, promoting HTN via lipotoxicity and increased oxylipin synthesis. We hypothesize that lipolytic activity in abdominal aortic PVAT (aaPVAT) is increased during HTN. Plasma and aaPVAT were harvested from Dahl SS rats fed a high-fat (HF) or a control (CON) diet for 8 (♂=20, ♀=20), 16 (♂=10, ♀=10) and 24 (♂=14, ♀=14) wks. Mean arterial pressure (MAP±SEM; mmHg) was measured with sphyngomanometry. Free FA (FFA), β-hydroxybutyrate (BHB), glucose, and triglycerides were quantified with the CataChemWell-T analyzer, and individual FA using HPLC–MS/MS (reported as ng/dL). Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and phosphorylated pHSL(Ser563) were quantified in the Abby Western Blot. HF increased MAP compared to CON by 8 (131.5 vs 119.51±2.52), 16 (139.34 vs 118.26±5.7), and 24 wks (168.56 vs 121.94±3.93). HF at 24 wks had higher MAP compared to 8 and 16 wks. HF increased FFA and BHB at all time points and glucose at 24 wks. Plasma triglycerides were increased in HF vs. CON, and ♂ had higher levels than ♀ at all time points. ATGL, basal lipolysis rate-limiting enzyme, increased in aaPVAT from HF ♂ by 2.2, 2.53, and 1.82-fold at 8, 16, and 24 wks, respectively, compared to CON. In HF ♀, ATGL increased (1.95-fold change) at 16 wks vs. 8 wks. HSL content increased in HF vs. CON at 16 wks (2.1-fold change) but not at 24 wks. In contrast, pHSL abundance and the pHSL:HSL ratio were not affected by diet at 16 wks; however, both were reduced by 35.2% at 24 wks in HF ♂ and ♀. Lipolytic activity in HF coincided with higher plasma arachidonic (AA) and linoleic acid (LA) at 8 (AA HF=19.93, CON= 16.13±1.3; LA HF=29.22, CON=21.74±2.7) and 16 wks (AA HF=14.83, CON=11.61±1.34; LA HF=22.84, CON=11.66±2.9). Sex had no effect on AA or LA concentrations. Our results provide evidence that hypertensive Dahl SS rats fed HF exhibit higher aaPVAT basal lipolysis that may be driven by ATGL. In contrast, demand lipolysis, controlled by HSL activity, is reduced. Dysregulated basal lipolysis may lead to alterations in PVAT FA trafficking, enhance AA availability, and promote the biosynthesis of inflammatory oxylipins, thus impairing its vasoactive functions.