Voprosy pitaniia · 2026
[The effect of sibutramine on the levels of leptin, ghrelin, and cytokines (IL-1β, IL-10, and IL-17A) in rats with induced obesity].
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Rieger N A, Trushina E N, Mustafina O K, Aksenov I V, Tutelyan V A
Аннотация
UNLABELLED: The main goal of treating obese patients is to reduce body weight. Sibutramine (Sib) - reuptake inhibitor of serotonin (5-HT), norepinephrine (NE) and dopamine (DA), acting at the hypothalamic area, leads to weight loss. The effect of Sib on the production of adipokines and cytokines has not been sufficiently studied. The aim of the research was to investigate the effect of Sib on changes in blood plasma levels of leptin (Lep), ghrelin (Ghr), and cytokines IL-1β, IL-17A, and IL-10 in male Wistar rats with obesity induced by a high-fat diet (HFD).
MATERIAL AND METHODS: 50 rats with an initial body weight of 112±2 g were divided into 5 groups. For 90 days, the rats of the control group (1) received the AIN93G diet. The rats of the experimental groups (2-5) were fed HFD (24% fat content or 45% of calories). Physical activity (PA) of moderate intensity has been introduced for groups 3 and 5 (treadmill, angle 100, speed 25 cm/s for 20 min). In groups 4 and 5, Sib in daily dose 1.0 mg/kg body weight was added. At the end, the total weight, the weight of adipose tissue, liver and spleen were determined. The heparinized blood was centrifuged and the plasma was stored at -80 °C. Apoptosis of hepatocytes was performed using flow cytometry on DxFLEX cytometer (Beckman Coulter). The levels of IL-1β, IL-10, IL-17A, Lep and Ghr were determined using sets on a Luminex 200. The ratio of levels of Lep to Ghr (Lep/Ghr) and IL-10 to IL17A (IL-10/IL17A) were calculated.
RESULTS: Rats on HFD with Sib supplementation (group 4) developed an obesity phenotype comparable to those in group 2. In group 4, compared with group 1, the levels of Lep were significantly increased (2.69 [1.94; 3.15] vs 1.18 [0.90; 1.38] pg/ml; p<0.01) while there was a decrease in the levels of Ghr (0.56 [0.37; 0.71] vs 1.45 [1.21; 2.15] pg/ ml; p<0.001), IL-1β (0.05 [0.04; 0.06] vs 0.08 [0.07; 0.10] pg/ml; p<0.05) and IL-17A (0.004 [0.002; 0.005] vs 0.007 [0.006; 0.009] pg/ml; p<0.01). Compared with the other samples, the highest medians of Lep/Ghr (4.27 [3.06; 6.30] vs 0.69 [0.61; 1.07], p<0.01) and IL-10/IL-17A (5.57 [2.12; 8.73] vs 1.57 [1.34; 2.25], p<0.05) were found in group 4. When Sib was combined with PA in group 5, the levels of adipokines, IL-1β, and Lep/Ghr and IL-10/IL-17A no longer differed from the control. Sib, by suppressing the reuptake of 5-HT, NE and DA, cancels changes in the levels of adipokines and cytokines caused by HFD with the return of Lep/Ghr and IL-10/IL-17A values to the control values only with regular PA.
CONCLUSION: The positive effect of Sib on the levels of adipokines and cytokines is manifested in combination with regular PA, even in induced obesity.
MATERIAL AND METHODS: 50 rats with an initial body weight of 112±2 g were divided into 5 groups. For 90 days, the rats of the control group (1) received the AIN93G diet. The rats of the experimental groups (2-5) were fed HFD (24% fat content or 45% of calories). Physical activity (PA) of moderate intensity has been introduced for groups 3 and 5 (treadmill, angle 100, speed 25 cm/s for 20 min). In groups 4 and 5, Sib in daily dose 1.0 mg/kg body weight was added. At the end, the total weight, the weight of adipose tissue, liver and spleen were determined. The heparinized blood was centrifuged and the plasma was stored at -80 °C. Apoptosis of hepatocytes was performed using flow cytometry on DxFLEX cytometer (Beckman Coulter). The levels of IL-1β, IL-10, IL-17A, Lep and Ghr were determined using sets on a Luminex 200. The ratio of levels of Lep to Ghr (Lep/Ghr) and IL-10 to IL17A (IL-10/IL17A) were calculated.
RESULTS: Rats on HFD with Sib supplementation (group 4) developed an obesity phenotype comparable to those in group 2. In group 4, compared with group 1, the levels of Lep were significantly increased (2.69 [1.94; 3.15] vs 1.18 [0.90; 1.38] pg/ml; p<0.01) while there was a decrease in the levels of Ghr (0.56 [0.37; 0.71] vs 1.45 [1.21; 2.15] pg/ ml; p<0.001), IL-1β (0.05 [0.04; 0.06] vs 0.08 [0.07; 0.10] pg/ml; p<0.05) and IL-17A (0.004 [0.002; 0.005] vs 0.007 [0.006; 0.009] pg/ml; p<0.01). Compared with the other samples, the highest medians of Lep/Ghr (4.27 [3.06; 6.30] vs 0.69 [0.61; 1.07], p<0.01) and IL-10/IL-17A (5.57 [2.12; 8.73] vs 1.57 [1.34; 2.25], p<0.05) were found in group 4. When Sib was combined with PA in group 5, the levels of adipokines, IL-1β, and Lep/Ghr and IL-10/IL-17A no longer differed from the control. Sib, by suppressing the reuptake of 5-HT, NE and DA, cancels changes in the levels of adipokines and cytokines caused by HFD with the return of Lep/Ghr and IL-10/IL-17A values to the control values only with regular PA.
CONCLUSION: The positive effect of Sib on the levels of adipokines and cytokines is manifested in combination with regular PA, even in induced obesity.