Perirenal adipose tissue (PRAT)-derived asprosin as a potential doorway to obesity-related insulin resistance in male mice
Authors: Jacob Berlin , Pita Marichelle , Maddie Nicole , Cai Weikang , Sepulveda Maria 
Published: May 2023

PRAT, a mixture of white (WAT) and brown adipose tissue (BAT), has been increasingly recognized as a metabolically active tissue able to secrete a series of adipokines. In obesity, PRAT undergoes changes in its secretory profile. Recent studies have reported that asprosin, a newly discovered adipokine secreted by white adipocytes, is elevated in obese individuals. Whether PRAT secretes asprosin remains unknown. We hypothesized that in obesity, PRAT undergoes phenotypic changes which lead to increased asprosin expression in association with insulin resistance. To address our hypothesis, eight-week-old male C57BL/6 mice were randomized into two experimental groups. The Control Group (n=7) received a standard chow diet (5% fat, 48.7% carbohydrates [3.2% sucrose]) and the Obese Group (n=11) received a Western Diet (WD) (40% fat, 43% carbohydrates [34% sucrose]) for 38 weeks. Our experimental model was validated by the presence of central obesity which was confirmed by increased waist circumference (10.79 ± 0.25 cm vs. 8.70 ± 0.16 cm controls, p<0.0001) and increased body weight (45.39 ± 1.98 g vs. 29.21 ± 0.79 g controls, p<0.0001). Metabolic studies revealed that obese mice developed an intolerance to glucose as determined by the glucose tolerance test (40907 ± 5324 a.u vs. 26741 ± 2380 a.u controls, p<0.05), elevated fasting blood glucose (116.9 ± 4.58 mg/dL vs. 88.0 ± 8.51 mg/dL controls, p<0.05) and high serum insulin levels (3.52 ± 0.63 ng/mL vs. 0.91 ± 0.36 ng/mL controls, n=6, p<0.01). Insulin resistance in the obese group was further confirmed by the increased homeostasis model assessment for insulin resistance (HOMA-IR) (35.99 ± 6.08 a.u vs. 4.24 ± 1.71 a.u controls, n=5, p<0.01). As expected, greater PRAT mass was detected in the obese group (17.42 ± 2.34 mg/g vs. 2.92 ± 0.43 mg/g controls, p<0.05) compared to controls. Histological analysis of PRAT stained with H&E demonstrated a marked reduction of BAT and expansion of WAT with increased size of white adipocytes (6555 ± 1253 μm2 vs 493.7 ± 15.33 μm2 controls, p<0.05) in association with inflammatory mononuclear cell infiltration. Strikingly, higher serum levels of asprosin (4.39 ± 0.07 pg/mL vs. 3.81 ±0.18 pg/mL controls, n=3, p<0.05) in obese mice was accompanied by increased asprosin expression within PRAT (1.28 ± 0.18 a.u vs. 0.63 ± 0.11 a.u, n=3, p<0.05). Since asprosin has been linked to insulin resistance in humans, our results suggest that insulin resistance observed in our male obese mice may be a result of increased circulating asprosin. The novelty of our findings indicate that PRAT may be a potential tissue contributing to the elevated circulating levels of asprosin in obesity. Diabetes Action 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.