The Targeted Impact of Flavones on Obesity-Induced Inflammation and the Potential Synergistic Role in Cancer and the Gut Microbiota

Abstract

Obesity is an inflammatory disease that is approaching pandemic levels, affecting nearly 30% of the world’s total population. Obesity increases the risk of diabetes, cardiovascular disorders, and cancer, consequentially impacting the quality of life and imposing a serious socioeconomic burden. Hence, reducing obesity and related life-threatening conditions has become a paramount health challenge. The chronic systemic inflammation characteristic of obesity promotes adipose tissue remodeling and metabolic changes. Macrophages, the major culprits in obesity-induced inflammation, contribute to sustaining a dysregulated immune function, which creates a vicious adipocyte–macrophage crosstalk, leading to insulin resistance and metabolic disorders. Therefore, targeting regulatory inflammatory pathways has attracted great attention to overcome obesity and its related conditions. However, the lack of clinical efficacy and the undesirable side-effects of available therapeutic options for obesity provide compelling reasons for the need to identify additional approaches for the prevention and treatment of obesity-induced inflammation. Plant-based active metabolites or nutraceuticals and diets with an increased content of these compounds are emerging as subjects of intense scientific investigation, due to their ability to ameliorate inflammatory conditions and offer safe and cost-effective opportunities to improve health. Flavones are a class of flavonoids with anti-obesogenic, anti-inflammatory and anti-carcinogenic properties. Preclinical studies have laid foundations by establishing the potential role of flavones in suppressing adipogenesis, inducing browning, modulating immune responses in the adipose tissues, and hindering obesity-induced inflammation. Nonetheless, the understanding of the molecular mechanisms responsible for the anti-obesogenic activity of flavones remains scarce and requires further investigations. This review recapitulates the molecular aspects of obesity-induced inflammation and the crosstalk between adipocytes and macrophages, while focusing on the current evidence on the health benefits of flavones against obesity and chronic inflammation, which has been positively correlated with an enhanced cancer incidence. We conclude the review by highlighting the areas of research warranting a deeper investigation, with an emphasis on flavones and their potential impact on the crosstalk between adipocytes, the immune system, the gut microbiome, and their role in the regulation of obesity.

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…A metagenomic analysis indicated that the tea extracts changed the gut microbiota’s composition [ 428 ]. In the same way also flavones ‘effects on obesity has been linked to gut microbiota modifications [ 338 ]. Oral hydroxysafflor yellow A (HSYA) reversed the HFD-induced gut microbiota dysbiosis and reduced the obese phenotype [ 429 ].…”

“…Some of the richest sources of flavones are parsley, celery, peppermint, and sage, which predominantly contain apigenin and luteolin as well as maize and citrus fruits. In general, flavones are found as glucosides in citrus fruits, vegetables, herbs and grains and although they represent a small fraction of the total flavonoid intake, they have shown health effects and anti-obesity properties [ 338 , 339 ]. As it is going to described latter, most of the studies that investigate the beneficial effects of flavones use them as aglycone and a scarce number of approaches deepen on the effects of flavones when consumed within the whole food and a feasible doses or in combination with other bioactive compounds.…”

“…Although flavones have been widely studied for their antioxidant and anti-inflammatory properties [ 338 ] their capacity to impact on adipose tissue metabolism and functionality cannot be underestimated.…”

Special Issue “Flavonoids and Their Disease Prevention and Treatment Potential”: Recent Advances and Future Perspectives

“…Therefore, reducing obesity and associated life-threatening diseases has become an emerging area of health sciences. In this Special Issue, Sudhakaran and Doseff have contributed to a comprehensive review of the impact of dietary flavones on obesity-induced inflammation [ 27 ]. The common flavones are luteolin, apigenin, chrysin, baicalin, acacetin, orientin, and apigenin, which could be found in food sources such as citrus fruits, vegetables, herbs, and grains.…”

Dietary Flavonoids in p53—Mediated Immune Dysfunctions Linking to Cancer Prevention

“…This is largely mediated by gut microbiota as it increases adiposity and fatty acid metabolism. Further, intestinal microbes modify flavonoids by glucosidation, dihydroxylation, and decarboxylation converting them into monomers, which can be more absorbable in the intestine [211]. To add, flavonoids isolated from mulberry leaves ameliorate lipid dysmetabolism in the high fat diet (HFD)-fed mice.…”