Proanthocyanidins at the gastrointestinal tract: mechanisms involved in their capacity to mitigate obesity-associated metabolic disorders.

The prevalence of overweight and obesity is continually increasing worldwide. Obesity is a major public health concern given the multiple associated comorbidities. Finding dietary approaches to prevent/mitigate these conditions is of critical relevance. Proanthocyanidins (PACs), oligomers or polymers of flavan-3-ols that are extensively distributed in nature, represent a major part of total dietary polyphenols. Although current evidence supports the capacity of PACs to mitigate obesity-associated comorbidities, the underlying mechanisms remain speculative due to the complexity of PACs' structure. Given their limited bioavailability, the major site of the biological actions of intact PACs is the gastrointestinal (GI) tract. This review discusses the actions of PACs at the GI tract which could underlie their anti-obesity effects. These mechanisms include: i) inhibition of digestive enzymes at the GI lumen, including pancreatic lipase, α-amylase, α-glucosidase; ii) modification of gut microbiota composition; iii) modulation of inflammation- and oxidative stress-triggered signaling pathways, e.g. NF-κB and MAPKs; iv) protection of the GI barrier integrity. Further understanding of the mechanisms and biological activities of PACs at the GI tract can contribute to develop nutritional and pharmacological strategies oriented to mitigate the serious comorbidities of obesity.