Melo B P, Zacarias A C, Oliveira J C C, de Souza Cordeiro L M, Horta N A C, Poletini M O, Tonoli C, Dos Santos M L, Wanner S P, Meeusen R, Heyman E, Avelar G F, Soares D D
Federal University of Minas Gerais, Department of Physical Education, Exercise Physiology Laboratory, Av. Pres. Antônio Carlos, 6627 Campus-Pampulha, Belo Horizonte, Brazil.
Federal University of Minas Gerais, Department of Physical Education, Exercise Physiology Laboratory, Av. Pres. Antônio Carlos, 6627 Campus-Pampulha, Belo Horizonte, Brazil.
Clin Nutr. 2025 Jan;44:166-177. doi: 10.1016/j.clnu.2024.11.043. Epub 2024 Dec 7.
Type 2 diabetes, characterized by hyperglycemia, is closely linked to obesity and low-grade inflammation. Acute cocoa flavanols (CF) intake has demonstrated benefits in vasoreactivity, cognitive functions, and antioxidant enzyme activity. However, the physiological mechanisms of CF concerning glucose uptake, inflammatory mediators, and their interplay with aerobic exercise remain unclear in populations with metabolic diseases.
This study aims to investigate the acute effects of CF, alone or combined with acute aerobic exercise on mechanisms involved in glucose uptake and inflammatory mediators in the liver, skeletal muscle, pancreas, and adipose tissue in insulin-resistant (IR) rats.
Sixty-four Wistar rats (250 ± 10g; 15 weeks age) were subjected to a regular chow (CON) or an obesity-associated insulin-resistant (IR) state induced by a high-fat diet and fructose-rich beverage for 30 days. Seventy-two hours after an incremental maximal treadmill running test, rats received a placebo solution or CF supplementation (45 mg·kg of body weight). One hour later, they either rested or ran on a treadmill at 60 % of peak oxygen uptake (VO) for 30 min. Euthanasia occurred 30 min post-experimental sessions. Inflammatory and anti-inflammatory cytokines were assayed using ELISA in the liver, pancreas, gastrocnemius muscle, and epididymal adipose tissues. TRB3 and CPT1 mRNA were assessed by q-RTPCR in the liver and gastrocnemius muscle while Akt and AMPK phosphorylation were examined by immunohistochemistry.
CF attenuated hyperglycemia observed after submaximal aerobic exercise in IR rats (p < 0.001). In the liver, CF exhibited additive effects to aerobic exercise, enhancing Akt protein phosphorylation, potentially contributing to improved glucose uptake in IR rats. Submaximal aerobic exercise and CF increased AMPK protein phosphorylation in the liver (p < 0.001) and skeletal muscle (p < 0.001), reduced TRB3 gene expression (p < 0.01), elevated CPT-1a gene expression (p < 0.001), and ameliorated the inflammatory milieu in the pancreas, adipose tissue, liver, and gastrocnemius muscle.
Acute intake, of CF combined with submaximal aerobic exercise activates key proteins and genes involved in glucose uptake and lipid metabolism, improving the inflammatory milieu. This synergistic effect may contribute to mitigating metabolic complications associated with insulin resistance.
2型糖尿病以高血糖为特征，与肥胖和低度炎症密切相关。急性摄入可可黄烷醇（CF）已显示出对血管反应性、认知功能和抗氧化酶活性有益。然而，在患有代谢疾病的人群中，CF在葡萄糖摄取、炎症介质及其与有氧运动相互作用方面的生理机制仍不清楚。
本研究旨在调查CF单独或与急性有氧运动联合对胰岛素抵抗（IR）大鼠肝脏、骨骼肌、胰腺和脂肪组织中葡萄糖摄取和炎症介质相关机制的急性影响。
64只Wistar大鼠（体重250±10g；15周龄）接受常规饲料（CON）喂养，或通过高脂饮食和富含果糖的饮料诱导30天建立肥胖相关胰岛素抵抗（IR）状态。在递增式最大跑步机跑步试验72小时后，大鼠接受安慰剂溶液或CF补充剂（45mg·kg体重）。1小时后，它们要么休息，要么以峰值摄氧量（VO）的60%在跑步机上跑步30分钟。实验结束后30分钟实施安乐死。使用酶联免疫吸附测定法（ELISA）检测肝脏、胰腺、腓肠肌和附睾脂肪组织中的炎性和抗炎细胞因子。通过定量逆转录聚合酶链反应（q-RTPCR）评估肝脏和腓肠肌中TRB3和CPT1 mRNA，同时通过免疫组织化学检测Akt和AMPK磷酸化。
CF减轻了IR大鼠次最大有氧运动后出现的高血糖（p<0.001）。在肝脏中，CF对有氧运动表现出相加作用，增强了Akt蛋白磷酸化，这可能有助于改善IR大鼠的葡萄糖摄取。次最大有氧运动和CF增加了肝脏（p<0.001）和骨骼肌（p<0.001）中AMPK蛋白磷酸化，降低了TRB3基因表达（p<0.01），提高了CPT-1a基因表达（p<0.001），并改善了胰腺、脂肪组织、肝脏和腓肠肌中的炎症环境。
急性摄入CF与次最大有氧运动联合激活了参与葡萄糖摄取和脂质代谢的关键蛋白和基因，改善了炎症环境。这种协同效应可能有助于减轻与胰岛素抵抗相关的代谢并发症。
