{
  "abstract": "Perivascular adipose tissue (PVAT) is a metabolically active adipose depot that surrounds most arterial beds and functions as an important regulator of vascular homeostasis. It exerts a potent anticontractile influence on small resistance arteries via the paracrine release of bioactive adipokines. However, in obesity, excessive caloric intake induces inflammation of adipose tissue depots, leading to PVAT dysfunction and predisposing individuals to hypertension and type 2 diabetes.We have previously shown, using a swimming model, that exercise restores PVAT function; however, the mechanism by which this occurs remains elusive. Some studies have reported that the beneficial effects of exercise on PVAT depots may vary between exercise modalities. As running is the most common form of exercise in the UK, we aimed to develop a treadmill model of exercise in mice and determine the mechanism by which PVAT function is restored.Male C57BL/6J mice were randomly assigned to three experimental groups: sedentary control (SC), sedentary obese (SO), and exercised obese (EO). Obese mice were fed a 60% kcal from fat diet from 8 weeks of age, and the EO group commenced training at 14 weeks. Body weight was recorded weekly, and body composition was assessed biweekly using EchoMRI. Both SO and EO mice exhibited significantly increased body weight compared to SC mice, and exercise did not induce weight or fat loss, nor did it increase lean mass. SO mice exhibited hypertension and glucose intolerance, both of which were reduced in EO mice.The mesenteric vascular bed was isolated, and resistance arteries (± PVAT; <200 µm diameter) were mounted in a wire myograph system to assess contractile responses to noradrenaline (NA; 1 × 10–9–3 × 10–4.5 M). In vessels from SC mice (n = 10), the contractile response to NA was attenuated in arteries with intact PVAT; this anticontractile effect was lost in the SO group (n = 10). However, in vessels from EO mice (n = 9), PVAT anticontractile function was restored. Using ELISA, plasma concentrations of the vasodilatory adipokine adiponectin were significantly elevated in EO mice compared with both SC and SO groups.Bulk RNA sequencing of PVAT depots revealed significant upregulation of cytokine and chemokine signalling pathways and enhanced immune responses in PVAT from SO mice, consistent with an inflamed phenotype (n = 3 per group). Following exercise, immune-related pathways were downregulated across PVAT, alongside increased lipid and fatty acid metabolic processes (n = 3 per group).In summary, restoration of PVAT function in obesity through treadmill exercise was independent of weight and fat loss. Exercise induced transcriptomic changes in PVAT that favoured reduced inflammation and an improved metabolic profile. Further studies will aim to delineate the molecular pathways underlying these functional improvements, which may aid in the development of therapies to promote an anti-inflammatory and vasodilatory PVAT phenotype, and reduce the incidence of hypertension and cardiovascular disease in obesity.",
  "authors": [
    {
      "affiliations": [
        "University of Manchester, Manchester, United Kingdom"
      ],
      "name": "Hannah Williamson"
    }
  ],
  "title": "308 Transcriptomic reprogramming of obese PVAT by exercise: anti-inflammatory pathways driving functional recovery",
  "uid": "d0f1e963-6eea-5fd7-bdca-69a2aef6a238"
}