Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.

Context: Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This vitamin makes up mitochondrial complexes and participates as an enzymatic cofactor in several mechanisms associated with energy metabolism. Objective: This systematic review collected and discussed the most relevant results on the role of riboflavin in the energy metabolism of lipids, proteins, and carbohydrates. Data Sources: A systematic search was carried out in the PubMed-Medline, Scopus, Embase, and Web of Science databases using the PICOS (Population, Intervention, Comparison, Outcome, Study design) strategy. Data Extraction: The screening of studies went through 2 stages following predefined eligibility criteria. The information extracted covered reference details, study design, population characteristics, experimental model, treatment parameters and dosage, route of administration, duration of treatment, and results found. Data Analysis: The risk of bias was assessed using the SYRCLE Risk of Bias (RoB) tool for in vivo studies and the QUIN tool adapted for in vitro studies, utilizing 10 domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases, to evaluate the methodological quality of the included studies. Conclusion: This review concludes that riboflavin regulates energy metabolism by activating primary metabolic pathways and is involved in energy balance homeostasis.

Background: Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation. Objectives: In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity. Methods: Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated. Results: Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration. Conclusion: These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation. GRAPHICAL ABSTRACT

Background: Cerebral palsy (CP) associates cerebral function damages with strong locomotor defects and premature sarcopenia. We previously showed that fibroblast growth factor 19 (FGF19) exerts hypertrophic effects on skeletal muscle and improves muscle mass and strength in mouse models with muscle atrophy. Facing the lack of therapeutics to treat locomotor dysfunctions in CP, we investigated whether FGF19 treatment could have beneficial effects in an experimental rat model of CP.Methods: Cerebral palsy was induced in male Wistar rat pups by perinatal anoxia immediately after birth and by sensorimotor restriction of hind paws maintained until Day 28. Daily subcutaneous injections with recombinant human FGF19 (0.1 mg/kg bw) were performed from Days 22 to 28. Locomotor activity and muscle strength were assessed before and after FGF19 treatment. At Day 29, motor coordination on rotarod and various musculoskeletal parameters (weight of tibia bone and of soleus and extensor digitorum longus (EDL) muscles; area of skeletal muscle fibres) were evaluated. In addition, expression of specific genes linked to human CP was measured in rat skeletal muscles.Results: Compared to controls, CP rats had reduced locomotion activity (−37.8% of distance travelled, P < 0.05), motor coordination (−88.9% latency of falls on rotarod, P < 0.05) and muscle strength (−25.1%, P < 0.05). These defects were associated with reduction in soleus (−51.5%, P < 0.05) and EDL (−42.5%, P < 0.05) weight, smaller area of muscle fibres, and with lower tibia weight (−38%, P < 0.05). In muscles from rats submitted to CP, changes in the expression levels of several genes related to muscle development and neuromuscular junctions were similar to those found in wrist muscle of children with CP (increased mRNA levels of Igfbp5, Kcnn3, Gdf8, and MyH4 and decreased expression of Myog, Ucp2 and Lpl). Compared with vehicle‐treated CP rats, FGF19 administration improved locomotor activity (+53.2%, P < 0.05) and muscle strength (+25.7%, P < 0.05), and increased tibia weight (+13.8%, P < 0.05) and soleus and EDL muscle weight (+28.6% and +27.3%, respectively, P < 0.05). In addition, it reduced a number of very small fibres in both muscles (P < 0.05). Finally, gene expression analyses revealed that FGF19 might counteract the immature state of skeletal muscles induced by CP.Conclusions: These results demonstrate that pharmacological intervention with recombinant FGF19 could restore musculoskeletal and locomotor dysfunction in an experimental CP model, suggesting that FGF19 may represent a potential therapeutic strategy to combat the locomotor disorders associated with CP.