Innovative Therapeutic Approaches Targeting Obesity: Can Flavonoids Improve the Efficacy of Anti-Obesogenic Drugs?

: Obesity is a chronic, multifactorial metabolic disease associated with various factors such as insulin resistance, increased adipogenesis, induction of gluconeogenesis, epigenetic mechanisms, chronic inflammatory state, and oxidative stress. Anti-obesity drugs such as Semaglutide and Tirzepatide are currently used in therapies for obese patients and exert remarkable anti-obesogenic effects, determining weight loss and inhibition of insulin resistance. The impairment of the adipogenesis process and the inhibition of the differentiation of human bone marrow mesenchymal stem cells into adipocytes should also be considered to improve the therapeutic strategies for obesity. Notably, the ability of several flavonoids to inhibit adipogenesis has been described. Flavonoids are the most abundant polyphenols in the human diet and exhibit a wide range of biological properties, including antioxidant and anti-inflammatory effects. Furthermore, many flavonoids can modulate the activity of enzymes involved in epigenetic mechanisms, which play a crucial role in obesity development. The purpose of this review is the identification of those flavonoids able to exert anti-adipogenic and anti-obesity effects in both in vitro and in vivo experimental models, with the aim of combining these natural molecules, as adjuvants, with anti-obesogenic drugs to develop innovative therapeutic approaches for the treatment of obesity pathology.