The prevention and treatment of obesity is primary based on the follow-up of a healthy lifestyle, which includes a healthy diet with an important presence of bioactive compounds such as polyphenols. For many years, the health benefits of polyphenols have been attributed to their anti-oxidant capacity as free radical scavengers. More recently it has been described that polyphenols activate other cell-signaling pathways that are not related to ROS production but rather involved in metabolic regulation. In this review, we have summarized the current knowledge in this field by focusing on the metabolic effects of flavonoids. Flavonoids are widely distributed in the plant kingdom where they are used for growing and defensing. They are structurally characterized by two benzene rings and a heterocyclic pyrone ring and based on the oxidation and saturation status of the heterocyclic ring flavonoids are grouped in seven different subclasses. The present work is focused on describing the molecular mechanisms underlying the metabolic impact of flavonoids in obesity and obesity-related diseases. We described the effects of each group of flavonoids in liver, white and brown adipose tissue and central nervous system and the metabolic and signaling pathways involved on them.

Maqui (Aristotelia Chilensis) berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT). These changes correlated with an increased expression of the carbohydrate response element binding protein b (Chrebpb), the sterol regulatory binding protein 1c (Srebp1c) and Cellular repressor of adenovirus early region 1A–stimulated genes 1 (Creg1) and an improvement in the fibroblast growth factor 21 (FGF21) signaling. Our evidence suggests that maqui dietary supplementation activates the induction of fuel storage and thermogenesis characteristic of a brown-like phenotype in scWAT and counteracts the unhealthy metabolic impact of an HFD. This induction constitutes a putative strategy to prevent/treat diet-induced obesity and its associated comorbidities.

Obesity is a worldwide health problem mainly due to its associated comorbidities. Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in metabolic homeostasis in healthy individuals and considered a promising therapeutic candidate for the treatment of obesity. FGF21 is predominantly produced by the liver but also by other tissues, such as white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle, and pancreas in response to different stimuli such as cold and different nutritional challenges that include fasting, high-fat diets (HFDs), ketogenic diets, some amino acid-deficient diets, low protein diets, high carbohydrate diets or specific dietary bioactive compounds. Its target tissues are essentially WAT, BAT, skeletal muscle, heart and brain. The effects of FGF21 in extra hepatic tissues occur through the fibroblast growth factor receptor (FGFR)-1c together with the co-receptor β-klotho (KLB). Mechanistically, FGF21 interacts directly with the extracellular domain of the membrane bound cofactor KLB in the FGF21- KLB-FGFR complex to activate FGFR substrate 2α and ERK1/2 phosphorylation. Mice lacking KLB are resistant to both acute and chronic effects of FGF21. Moreover, the acute insulin sensitizing effects of FGF21 are also absent in mice with specific deletion of adipose KLB or FGFR1. Most of the data show that pharmacological administration of FGF21 has metabolic beneficial effects. The objective of this review is to compile existing information about the mechanisms that could allow the control of endogenous FGF21 levels in order to obtain the beneficial metabolic effects of FGF21 by inducing its production instead of doing it by pharmacological administration.

The metabolic response to a maximal exercise test in physically inactive adults remains poorly understood, particularly regarding the role of adiponectin, an adipokine with insulin-sensitizing and anti-inflammatory properties. Adiponectin circulates in three isoforms—low (LMW), medium (MMW), and high-molecular-weight (HMW)—with differing bioactivities. While exercise is known to influence adiponectin levels, evidence is conflicting, and few studies have explored isoform-specific changes. This study aimed to evaluate the effects of a single maximal exercise session on circulating adiponectin isoforms and their associations with metabolic and kidney function markers in physically inactive young adults. In this quasi-experimental study, twenty-one physically inactive participants (mean age 24.6 ± 2.1 years, 85.7% women) completed a progressive cycle ergometer test. Circulating levels of LMW and MMW adiponectin, metabolic outcomes (e.g., cholesterol, triglycerides, fibroblast growth factor 21 (FGF21)), and kidney function markers (e.g., creatinine, proteinuria) were assessed before and after exercise using biochemical assays and Western blotting. Comparisons between pre- and post-exercise values were made with the Wilcoxon test. Exercise increased lipid metabolism markers (total cholesterol, triglycerides, HDL) and kidney stress indicators (albuminuria, proteinuria) (p < 0.05). LMW and MMW adiponectin levels showed no significant overall changes, but LMW adiponectin positively correlated with changes in total cholesterol and FGF21, while MMW adiponectin negatively correlated with creatinine and proteinuria (p < 0.05). HMW adiponectin was undetectable by our methods. A single maximal exercise session revealed isoform-specific associations between adiponectin and metabolic or kidney stress markers, emphasizing the complex role of adiponectin in exercise-induced metabolic responses. Future research should explore mechanisms underlying these differential associations to optimize exercise interventions for metabolic health improvement.

Obesity is a significant global health issue, profoundly affecting metabolic and cardiovascular health and other related chronic conditions. In Chile, the prevalence of obesity is among the highest within the Organisation for Economic Cooperation and Development (OECD) countries, highlighting a critical public health challenge. This narrative review examines current evidence on the independent and potential synergistic roles of omega-3 fatty acids and exercise in managing obesity-related metabolic dysfunction. Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), have been shown to lower triglyceride levels, enhance lipid metabolism, and modulate inflammation via pathways involving peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding protein-1c (SREBP-1c). Exercise interventions, such as moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), provide distinct yet complementary metabolic benefits. Specifically, MICT improves body fat distribution and mitochondrial efficiency, whereas HIIT has notable effects on metabolic adaptability and insulin signaling. Additionally, emerging evidence points toward a potential role of the kinin-kallikrein system, particularly kallikrein 7 (KLK7), in obesity-associated insulin resistance. Despite these promising findings, several knowledge gaps persist regarding optimal dosing, intervention timing, population-specific effects, and the exact mechanisms behind the potential synergistic interactions between omega-3 supplementation and structured exercise. This review emphasizes the importance of conducting further research, particularly controlled clinical trials, to clarify these combined interventions’ effectiveness and establish targeted therapeutic strategies tailored to individual metabolic profiles.