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Updated: Jun 12, 2026
Isolation, Culture, and Adipogenic Induction of Stromal Vascular Fraction-derived Preadipocytes from Mouse Periaortic Adipose Tissue
Published on: July 21, 2023
Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese C57Bl/6
Juha Ketonen1, Jin Shi, Essi Martonen
1School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Background:
Biological substances derived from perivascular fat modulate vascular tone, thus alterations in periadventitial adipose tissue (PVAT) may aggravate endothelial dysfunction in obesity.
Methods And Results:
Male C57Bl/6 mice were fed either a high-fat diet or standard laboratory chow for 8 months. Vascular responses were studied in organ bath chambers from abdominal aortic ring preparations in the absence or presence of PVAT. The amount of PVAT as well as the cross-sectional area of adipocytes were increased in obese mice. In the presence of PVAT, obese aortas displayed impaired endothelium-dependent vasodilation whereas endothelium-independent vasodilatation was unaltered. Endothelium-dependent vasodilatation was restored after removal of PVAT and after reducing superoxide and hydrogen peroxide formation in the vascular wall by Tiron or polyethylene-glycol-catalase, respectively. PVAT from obese mice showed increased formation of hydrogen peroxide and superoxide. The PVAT-derived oxidative stress was abolished by pretreatment with the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase inhibitor, apocynin. The anti-contractile function of PVAT found in lean mice was completely abolished in obese mice, but partially restored after pretreatment with Tiron. The mRNA expressions of monocyte chemotactic protein-1, leptin and NADPH oxidase were markedly higher in the PVAT of obese than lean mice.
Conclusions:
PVAT promotes endothelial dysfunction in diet-induced obese C57Bl/6 mice via mechanisms that are linked to increased NADPH oxidase-derived oxidative stress and increased production of pro-inflammatory cytokines.
Insights
Perivascular fat (PVAT) in obese mice promotes endothelial dysfunction through increased oxidative stress and inflammation. Removing PVAT or inhibiting NADPH oxidase restored normal vascular function, highlighting PVAT
Area of Science:
- Cardiovascular Biology
- Adipose Tissue Biology
- Vascular Physiology
Background:
- Perivascular adipose tissue (PVAT) influences vascular tone.
- Obesity-associated alterations in PVAT may contribute to endothelial dysfunction.
Purpose of the Study:
- To investigate the role of PVAT in diet-induced obesity and endothelial dysfunction.
- To elucidate the mechanisms by which PVAT affects vascular function in obesity.
Main Methods:
- Diet-induced obesity model in C57Bl/6 mice (high-fat diet vs. control).
- Vascular reactivity studies using isolated aortic ring preparations.
- Assessment of oxidative stress markers (superoxide, hydrogen peroxide) and NADPH oxidase activity.
- Analysis of pro-inflammatory cytokine mRNA expression in PVAT.
Main Results:
- Obese mice exhibited increased PVAT mass and adipocyte size.
- PVAT from obese mice impaired endothelium-dependent vasodilation, which was restored upon PVAT removal or antioxidant treatment.
- PVAT in obese mice showed elevated superoxide and hydrogen peroxide production, linked to NADPH oxidase activity.
- Anti-contractile function of PVAT was lost in obesity but partially recovered with antioxidant treatment.
- Increased mRNA expression of MCP-1, leptin, and NADPH oxidase was observed in obese PVAT.
Conclusions:
- PVAT contributes to endothelial dysfunction in diet-induced obesity.
- Mechanisms involve increased NADPH oxidase-derived oxidative stress and pro-inflammatory cytokine production.
- Targeting PVAT-derived oxidative stress may offer therapeutic potential for obesity-related vascular complications.
