Abstract
Evidence suggests that polyphenol-rich diets enhance insulin sensitivity; however, their molecular mechanisms in human adipose tissue remain incompletely understood. We investigated whether habitual intake of total polyphenols and their major subclasses is associated with the expression of PI3K, Akt, and PTEN, key components of the PI3K/Akt insulin-signaling pathway, in visceral and subcutaneous adipose tissue (VAT and SAT) of adults with obesity, and how these associations relate to markers of insulin sensitivity. In this cross-sectional study, 135 adults with obesity (BMI ≥ 30 kg/m2), aged ≥ 18 years, undergoing elective abdominal surgery, provided paired VAT and SAT samples. Dietary polyphenol intake was estimated using a validated food-frequency questionnaire (FFQ), and gene expression was quantified by RT-qPCR. Fasting insulin concentrations were measured, and insulin resistance was estimated using the HOMA-IR index. Higher total polyphenol intake was associated with lower expression of PI3K, Akt, and PTEN, with depot- and subclass-specific patterns. Total polyphenols and stilbenes were inversely related to Akt expression in both VAT and SAT, while flavonoids, particularly anthocyanins and flavanones, showed additional downregulation in SAT. PI3K expression decreased in both depots with higher polyphenol intake, driven primarily by stilbenes in VAT and by flavonoids, anthocyanins, and flavanones in SAT. PTEN expression was reduced in SAT among participants with higher total polyphenol and stilbene intakes, and in VAT with greater hydroxycinnamic acid intake. In adults with obesity, higher dietary polyphenol intake was associated with altered expression of key genes involved in the PI3K/Akt insulin-signaling pathway in adipose tissue. These associations appeared to be depot-specific and varied across polyphenol subclasses, suggesting potential interactions between dietary polyphenols and adipose tissue insulin-signaling-related gene expression.