Lifestyle factors, especially diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given their anti-oxidant and anti-inflammatory actions. In fact, polyphenols can prevent or reverse the progression of disease processes through many distinct mechanisms. In particular, the crosstalk between polyphenols and gut microbiota, recently unveiled thanks to DNA-based tools and next generation sequencing, unravelled the central regulatory role of dietary polyphenols and their intestinal micro-ecology metabolites on the host energy metabolism and related illnesses. The objectives of this review are to: (1) provide an understanding of classification, structure, and bioavailability of dietary polyphenols; (2) underline their metabolism by gut microbiota; (3) highlight their prebiotic effects on microflora; (4) discuss the multifaceted roles of their metabolites in CMD while shedding light on the mechanisms of action; and (5) underscore their ability to initiate host epigenetic regulation. In sum, the review clearly documents whether dietary polyphenols and micro-ecology favorably interact to promote multiple physiological functions on human organism.

Polyphenols (PLPs), phytochemicals found in a wide range of plant-based foods, have gained extensive attention in view of their antioxidant, anti-inflammatory, immunomodulatory and several additional beneficial activities. The health-promoting effects noted in animal models of various non-communicable diseases explain the growing interest in these molecules. In particular, in vitro and animal studies reported an attenuation of lipid disorders in response to PLPs. However, despite promising preclinical investigations, the effectiveness of PLPs in human dyslipidemia (DLP) is less clear and necessitates revision of available literature. Therefore, the present review analyzes the role of PLPs in managing clinical DLP, notably by dissecting their potential in ameliorating lipid/lipoprotein metabolism and alleviating hyperlipidemia, both postprandially and in long-term interventions. To this end, PubMed was used for article search. The search terms included polyphenols, lipids, triglycerides, cholesterol, LDL-cholesterol and /or HDL-cholesterol. The critical examination of the trials published to date illustrates certain benefits on blood lipids along with co-morbidities in participant’s health status. However, inconsistent results document significant research gaps, potentially owing to study heterogeneity and lack of rigor in establishing PLP bioavailability during supplementation. This underlines the need for further efforts in order to elucidate and support a potential role of PLPs in fighting DLP.

Background and Aims: The increasing prevalence and absence of effective global treatment for metabolic syndrome (MetS) are alarming given the potential progression to severe non-communicable disorders such as type 2 diabetes and nonalcoholic fatty liver disease. The purpose of this study was to investigate the regulatory role of glycomacropeptide (GMP), a powerful milk peptide, in insulin resistance and liver dysmetabolism, two central MetS conditions. Materials and Methods: C57BL/6 male mice were fed a chow (Ctrl), high-fat, high-sucrose (HFHS) diet or HFHS diet along with GMP (200 mg/kg/day) administered by gavage for 12 weeks. Results: GMP lowered plasma insulin levels (in response to oral glucose tolerance test) and HOMA-IR index, indicating a more elevated systemic insulin sensitivity. GMP was also able to decrease oxidative stress and inflammation in the circulation as reflected by the decline of malondialdehyde, F2 isoprostanes and lipopolysaccharide. In the liver, GMP raised the protein expression of the endogenous anti-oxidative enzyme GPx involving the NRF2 signaling pathway. Moreover, the administration of GMP reduced the gene expression of hepatic pro-inflammatory COX-2, TNF-α and IL-6 via inactivation of the TLR4/NF-κB signaling pathway. Finally, GMP improved hepatic insulin sensitization given the modulation of AKT, p38 MAPK and SAPK/JNK activities, thereby restoring liver homeostasis as revealed by enhanced fatty acid β-oxidation, reduced lipogenesis and gluconeogenesis. Conclusions: Our study provides evidence that GMP represents a promising dietary nutraceutical in view of its beneficial regulation of systemic insulin resistance and hepatic insulin signaling pathway, likely via its powerful antioxidant and anti-inflammatory properties.

While the prevalence of metabolic syndrome (MetS) is steadily increasing worldwide, no optimal pharmacotherapy is readily available to address its multifaceted risk factors and halt its complications. This growing challenge mandates the development of other future curative directions. The purpose of the present study is to investigate the efficacy of cranberry proanthocyanidins (PACs) in improving MetS pathological conditions and liver complications; C57BL/6J mice were fed either a standard chow or a high fat/high sucrose (HFHS) diet with and without PACs (200 mg/kg), delivered by daily gavage for 12 weeks. Our results show that PACs lowered HFHS-induced obesity, insulin resistance, and hyperlipidemia. In conjunction, PACs lessened circulatory markers of oxidative stress (OxS) and inflammation. Similarly, the anti-oxidative and anti-inflammatory capacities of PACs were noted in the liver in association with improved hepatic steatosis. Inhibition of lipogenesis and stimulation of beta-oxidation could account for PACs-mediated decline of fatty liver as evidenced not only by the expression of rate-limiting enzymes but also by the status of AMPKα (the key sensor of cellular energy) and the powerful transcription factors (PPARα, PGC1α, SREBP1c, ChREBP). Likewise, treatment with PACs resulted in the downregulation of critical enzymes of liver gluconeogenesis, a process contributing to increased rates of glucose production in type 2 diabetes. Our findings demonstrate that PACs prevented obesity and improved insulin resistance likely via suppression of OxS and inflammation while diminishing hyperlipidemia and fatty liver disease, as clear evidence for their strength of fighting the cluster of MetS abnormalities.

There is currently a growing interest in the use of nutraceuticals as a means of preventing the development of complex diseases. Given the considerable health potential of milk-derived peptides, the aim of this study was to investigate the protective effects of glycomacropeptide (GMP) on metabolic syndrome. Particular emphasis was placed on the potential mechanisms mitigating cardiometabolic disorders in high-fat, high-fructose diet-fed mice in the presence of GMP or Bipro, an isocaloric control. The administration of GMP for 12 weeks reduced obesity, hyperglycemia and hyperinsulinemia caused by a high-fat, high-fructose diet, resulting in a decline in insulin resistance. GMP also lessened systemic inflammation, as indicated by decreased circulating inflammatory cytokines. In the intestinal and hepatic tissues, GMP improved homeostasis by increasing insulin sensitivity and attenuating high-fat, high-fructose-induced inflammation, oxidative stress and endoplasmic reticulum stress. Biochemical and histological analyses revealed improved hepatic steatosis and fatty acid composition in the livers of high-fat, high-fructose diet-fed mice treated with GMP compared to Bipro. A trend toward a decrease in bile acids without any marked changes in intestinal microbiota composition characterized GMP-treated animals compared to those administered Bipro. GMP offers considerable potential for fighting metabolic syndrome-related components and complications given its beneficial effects on risk factors such as inflammation, oxidative stress and endoplasmic reticulum stress without involving the intestinal microbiota.

Metabolic syndrome (MetS) constitutes a spectrum of interconnected conditions comprising obesity, dyslipidemia, hypertension, and insulin resistance (IR). While a singular, all-encompassing treatment for MetS remains elusive, an integrative approach involving tailored lifestyle modifications and emerging functional food therapies holds promise in preventing its multifaceted manifestations. Our main objective was to scrutinize the efficacy of cranberry proanthocyanidins (PAC, 200 mg/kg/day for 12 weeks) in mitigating MetS pathophysiology in male mice subjected to standard Chow or high-fat/high-fructose (HFHF) diets while unravelling intricate mechanisms. The administration of PAC, in conjunction with an HFHF diet, significantly averted obesity, evidenced by reductions in body weight, adiposity across various fat depots, and adipocyte hypertrophy. Similarly, PAC prevented HFHF-induced hyperglycemia and hyperinsulinemia while also lessening IR. Furthermore, PAC proved effective in alleviating key risk factors associated with cardiovascular diseases by diminishing plasma saturated fatty acids, as well as levels of triglycerides, cholesterol, and non-HDL-C levels. The rise in adiponectin and drop in circulating levels of inflammatory markers showcased PAC’s protective role against inflammation. To better clarify the mechanisms behind PAC actions, gut–liver axis parameters were examined, showing significant enhancements in gut microbiota composition, microbiota-derived metabolites, and marked reductions in intestinal and hepatic inflammation, liver steatosis, and key biomarkers associated with endoplasmic reticulum (ER) stress and lipid metabolism. This study enhances our understanding of the complex mechanisms underlying the development of MetS and provides valuable insights into how PAC may alleviate cardiometabolic dysfunction in HFHF mice.