Epicatechin and High-Molecular Weight Fraction Do Not Recapitulate the Antiobesity and Antidiabetes Activities of Whole Cocoa Extract

Cocoa flavanols show promise for inhibiting type 2 diabetes (T2D). The components responsible for this remain poorly understood. We compared cocoa extract (CE) supplementation against matched epicatechin (EC) or a high-molecular-weight fraction (HMW) in a T2D mouse model induced by high-fat (HF) plus streptozotocin (STZ). Mice were fed HF diet with STZ alone or with CE, EC, or HMW. HF + STZ animals fed CE had blunted weight gain and reduced insulin resistance compared to HF + STZ control as measured by the homeostasis model assessment of insulin resistance. However, these improvements are driven by reduced fasting glucose and insulin, as peripheral insulin resistance was not observed in the model when accounting for the fasting glucose. HF + STZ-induced dysbiosis was partially reversed by CE and HMWs. These findings demonstrate the beneficial effects of CE on the gut microbiome and cardiometabolic markers, which were not fully achieved by EC or HMW, suggesting synergistic effects of flavanols.