The research yielded 2,252 articles. This number was reduced after the application of an automatic function to remove duplicates (Microsoft Excel) and further checked manually leaving a total of 1,270 articles to be submitted to the first phase of screening by the application of eligibility criteria (Fig. 1). After applying the first round of exclusion criteria (title and abstract), a total of 884 articles were excluded, leaving 386 articles to be assessed by reading the full text. In the second round, 330 were excluded after full-text screening, as they did not meet the previously defined inclusion criteria. The remaining 56 articles were included in this review and sent for data extraction (S2).

Prisma flow diagram of the systematic review

The main characteristics of the studies are reported in Table 2. Thirty-one studies used single phenolic compounds, eighteen tested only PP-rich extracts (or PP-rich fractions), and seven studies used both extracts and single compounds.

The studies investigated the effects of various classes of (poly)phenols, including flavonols (n = 8) [10,11,12,13,14,15,16,17], flavanones (n = 6) [10, 13, 18,19,20,21], flavanonols (n = 2) [12, 22], flavones (n = 7) [12, 13, 23,24,25,26,27], flavan-3-ols (n = 6) [10, 28,29,30,31,32], isoflavones (n = 2) [21, 33], anthocyanins (n = 1) [34], stilbenes (n = 11) [13, 35,36,37,38,39,40,41,42,43,44], and phenolic acids (n = 3) [13, 45, 46].

The concentrations of the PPs tested in the different studies varied in the range of 0.001-600 µM, with some studies using different units of measurement (e.g. µg mL− 1 or ppm). Studies were divided based on the concentration of compounds into two categories: studies using physiological concentrations (≤ 2 µM), which can be found in human plasma after the consumption of dietary portions of PP-rich foods, and pharmacological concentrations (> 2 µM), which could theoretically be achieved through supplementation. Most of the studies used pharmacological concentrations of PPs to treat adipocytes. Specifically, only seven studies tested concentrations close to physiological ones or slightly above (≤ 2 µM).

Overall, the most frequently investigated PP classes were stilbenes, flavonols, flavones, flavanones, and flavan-3-ols. Among these, resveratrol (stilbene), quercetin (flavonol), and genistein (isoflavone) were the most tested individual compounds. These PPs are not only widely studied but are also abundant in common dietary sources, such as red grape (resveratrol, 0.16-24 mg/100 g), onions (quercetin, ~ 300 mg/100 g), and soy (genistein, 5.6 to 276 mg/100 g,) [66,67,68]. In addition, several studies investigated the effects of PP-rich extracts, including those derived from commonly consumed foods, such as berries. However, it is important to highlight that the use of extracts and/or fractions in cellular models such as adipocytes may raise concerns regarding biological plausibility. In fact, from a physiological point of view, complex food extracts undergo extensive digestion, absorption, metabolism, and biotransformation, particularly in intestinal and hepatic compartments, before reaching peripheral tissues. As a result, it is highly unlikely that raw extracts, as applied directly to cultured adipocytes, would come into contact with adipose tissue in vivo in their original form. This limits the translational relevance of such experiments in an in vivo context. Therefore, while these studies can provide valuable mechanistic insights, their results should be interpreted with caution in terms of dietary applicability. Highlighting these considerations, as well as the most frequently studied and diet-relevant PPs, may enhance the practical value and interpretability of the findings.

The following sections summarize the effects of extracts and compounds on lipid storage and glucose uptake and identify the main mechanisms of action by which different classes of (poly)phenols affect lipid and glucose metabolism (S2).

Adipocytes play a crucial role in energy storage by accumulating triacylglycerols (TAGs) in cytosolic lipid droplets. The TAGs are mobilized and broken down into fatty acids and glycerol when the body requires energy. Lipid storage is evaluated in cell culture, particularly in adipose cells, primarily through staining techniques targeting cellular lipids (e.g., Oil Red O assay) and by assays that involve the isolation and quantification of intracellular TAGs.

In this review, thirty-one studies investigated the effects of PPs on intracellular lipid content (lipid accumulation and/or TG content) [11,12,13,14, 16, 18, 22, 23, 25, 28,29,30, 34, 36, 37, 39, 41,42,43,44, 47, 49, 50, 52,53,54,55,56,57,58, 65]. Only three papers reported that (poly)phenols were unable to affect intracellular lipids [11, 53, 65] and one study showed an increase in lipids after treatment with PP extracts [28]. The remaining papers evidenced a reduction of intracellular lipid content after treatment with PPs. The reduction of cellular lipids was evidenced in eleven papers after treatment with PP-rich extracts, while nineteen studies evidenced an effect on lipids exerted by single phenolic compounds. Cellular lipid reduction was consistent across different classes of (poly)phenols, including flavonols (e.g., myricetin, rutin, kaempferol, quercetin and metabolites) [11,12,13,14], flavones (e.g., luteolin, isoorientin, apigenin) [12, 13, 23, 25], anthocyanins [34], flavanones (e.g., naringin, hesperidin) [13, 18], flavanonols (e.g., ampelopsin, taxifolin) [12, 22], phenolic acids (e.g., p-coumaric acid, ellagic acid, ferulic acid, gallic acid, vanillic acid, chlorogenic acid) [13], and stilbenes (e.g., piceatannol, resveratrol) [13, 36, 37, 39, 41,42,43,44]. However, there is not sufficient experimental evidence to conclude that certain PPs are particularly effective in reducing lipid content in mature adipocytes. From a physiological perspective, PP-extracts are unlikely to reach adipocytes in their native form; therefore, studies investigating the effects of individual compounds are more relevant in terms of mechanistic plausibility. Finally, it should be noted that most of the available findings, particularly those involving single compounds, have been obtained using supraphysiological or pharmacological concentrations.

Lipolysis is a crucial metabolic process involving the hydrolysis of triglycerides into non-esterified fatty acids (NEFA) and glycerol [69]. Catecholamines, including norepinephrine (NE) and epinephrine, are the main physiological stimulators of lipolysis, while other ho