Enhancing metabolic and inflammatory status in insulin-resistant rats: Acute intervention with cocoa flavanols and submaximal aerobic exercise activates intracellular signaling pathways for glucose metabolism

Introduction: 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.

Objective: 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.

Methods: 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^-1 of body weight). One hour later, they either rested or ran on a treadmill at 60 % of peak oxygen uptake (VO_2peak) 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.

Results: 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.

Conclusion: 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.