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It has been estimated that by 2030, half of all Americans will be obese. Increased total peripheral vascular resistance (TPR) is a major complication in obesity, though its mechanisms remain unclear. Adipose tissue undergoes phenotypic changes in obesity, and is closely correlated with vascular complications. One fat depot that has gained major attention is mWAT, which surrounds the mesenteric resistance arteries. Whether mWAT is associated with increased TPR remains under-investigated. We hypothesize that phenotypic changes in mWAT correlate with increased TPR in obesity.To address our hypothesis, we used a model of Western Diet (WD)-induced obesity in mice. Eight-week-old C57BL/6 female mice were randomized into Control and Obese groups. The control group (n=9) were fed a standard chow diet consisting of 48.7% Carbohydrate [3.15% Sucrose] and 5.0% Lipid, while the obese group (n=10) were fed a 50.0% Carbohydrate [34.1% Sucrose] and 21% Lipid WD for 58 weeks. Glucose metabolism and cardiovascular parameters were obtained during the experimental protocol. At terminal experiments, mWAT was collected for histological analysis.Obesity was confirmed in the obese group at 24 weeks by increased body weight (34.36 ± 1.25 g vs 24.69 ± 0.44 g controls, p<0.05), body mass index (BMI: 0.35 ± 0.01 kg/m2 vs 0.31 ± 0.01 kg/m2 controls, p<0.05), and waist circumference (9.16 ± 0.21 cm vs 7.56 ± 0.12 cm controls, p<0.05). As expected, obese mice exhibited increased fasting blood glucose (143.10 ± 4.31 mg/dL vs 95.00 ± 3.80 mg/dL, p<0.05), and intolerance to glucose detected by glucose tolerance test (30044.00 ± 1857.76 a.u. vs 22815.00 ± 2261.22 a.u. controls, p<0.05). Despite the presence of impaired glucose metabolism, obese females did not develop type 2 diabetes, as confirmed by normal HbA1C levels (4.33 ± 0.20 a.u. vs 4.27 ± 0.15 a.u. controls, p=0.803). Mean arterial blood pressure (MAP), obtained using radiotelemetry, and cardiac output (CO), measured via echocardiogram, were obtained to calculate TPR (TPR=MAP/CO). While obese female mice showed an increased MAP (122.94 ± 1.84 mmHg vs 112.51 ± 3.88 mmHg controls, n=5, p<0.05), CO remained unchanged (15.96 ± 1.96 mL/min vs. 15.65 ± 1.10 mL/min controls, n=5, p=0.884). Preliminary results reveal that obese females have a greater increase in TPR in comparison to controls (6.34 ± 0.77 mmHg·min/mL vs. 6.12 ± 0.46 mmHg·min/mL controls, n=2 per group). Since mWAT surrounds mesenteric resistance arteries, which are the main group of arteries contributing to TPR, we next examined mWAT by histological staining with H&E, which showed a significant increase in adipocyte size (2888.79 ± 575.20 μm2 vs 671.51 ± 10.31 μm2 controls, p<0.05) and inflammatory mononuclear cell infiltration in the obese group.Taken together, our results show an association between phenotypic changes in mWAT and increased TPR, suggesting mWAT as a potential culprit contributing to vascular complications in obesity. Diabetes Action Grant to Maria Alicia Carrillo Sepulveda This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.