Maria Vittoria Micioni Di Bonaventura

Chronic low-grade inflammation (metaflammation) is a key contributor to obesity-associated metabolic disorders and their cardiovascular complications. This study investigated the effects of CXT29, a novel dual cyclooxygenase-2 (COX-2) inhibitor and thromboxane prostanoid receptor (TP) antagonist, in comparison with its parent compound etodolac, in a murine model of diet-induced metabolic dysfunction. Four-week-old male C57BL/6 mice were fed either a standard diet or a high-fat diet for 18 weeks and subsequently treated with etodolac (20 mg/kg/day) or CXT29 (25 mg/kg/day) by oral gavage for 5 weeks. High-fat-diet-fed mice developed increased body weight, impaired glucose tolerance, altered circulating metabolic hormones, liver dysfunction, steatosis, inflammatory cell infiltration, and systemic inflammation. Both treatments attenuated systemic inflammation and improved the metabolic alterations induced by the obesogenic diet. Notably, CXT29, but not etodolac, attenuated the increase in circulating plasminogen activator inhibitor-1 (PAI-1), a biomarker associated with cardiovascular risk. These findings indicate that pharmacological inhibition of COX-2 improves metabolic dysfunction associated with diet-induced obesity. Furthermore, the additional TP antagonism provided by CXT29 does not compromise the metabolic benefits associate with COX-2 inhibition, while displaying a distinct effect on circulating PAI-1, supporting further investigation of this dual-target approach in obesity-associated metabolic dysfunction.

Overweight and obesity remain major global health challenges and are closely associated with metabolic disturbances, including dyslipidemia, insulin resistance, hypertension, and chronic low-grade inflammation. Dietary patterns rich in fruits and vegetables contribute to metabolic health, partly due to their complex matrix of bioactive compounds. Tart cherries ( Prunus cerasus , TC) are widely consumed in fresh and processed forms and have attracted attention for their potential benefits in obesity-related conditions. This review critically summarizes current evidence from in vitro , animal, and human studies investigating the effects of tart cherries and their derived products in overweight and obese individuals (BMI ≥ 25 kg/m ² ). Animal studies consistently reported anti-inflammatory, antioxidant, and metabolic improvements following tart cherry supplementation. In humans, the evidence suggested potential benefits for blood pressure and selected inflammatory markers, whereas findings regarding lipid profile, glucose metabolism, and body composition remain inconsistent. Overall, tart cherries may favorably influence metabolic and vascular processes associated with obesity; however, heterogeneity in study design, dosage, and product form limits definitive conclusions. Further research should focus on identifying the key bioactive components, understanding their bioavailability and mechanisms of action, and determining which populations may benefit most from TC-based interventions.

Cannabidiol (CBD) is one of the most abundant phytocannabinoids isolated from the Cannabis sativa plant. CBD is a lipophilic, non‐intoxicating substance that differently from Δ⁹‐tetrahydrocannabinol (Δ⁹‐THC) does not present the typical profile of a drug of abuse. It shows powerful anti‐inflammatory and anti‐oxidative properties that might be helpful for treating several pathologies. The aim of this review is to describe the potential role of CBD in the control of food intake and metabolism, with implications for the treatment of obesity and metabolic syndrome, and to discuss the underlying potential mechanisms of action. The preclinical evidence mentioned reveals that CBD influences eating behaviour, exerting anorexigenic effects and affecting the non‐homeostatic aspect of food intake, via modulation of dopamine signalling in the brain reward system. Data from animal models of diet‐induced obesity (DIO) and metabolic syndrome show that CBD improves glucose and lipid metabolism, inflammation and ameliorates psychiatric alterations not only in obese animals but also in the offspring born from obese mothers. These effects are achieved targeting multiple proteins expressed both in the central nervous system and peripheral tissues. The evidence collected from preclinical research, together with preliminary findings from clinical studies, supports further investigation of CBD in the context of obesity, metabolic syndrome and binge eating behaviour. Future studies are strongly required to highlight the potential role of CBD in these pathologies, specifically to better understand its mechanism of action, and how factors like sex differences, route of administration and formulation might influence the therapeutic activity of CBD.

The kidney plays a crucial role in the complex inter-organ communication that occurs during obesity, leading to the development of oxidative stress, inflammation, and fibrosis. Dysfunction of the transient receptor potential (TRP) ion channels contributes to this pathophysiology. This study was designed to evaluate the effects of antioxidant-rich fruit tart cherry (Prunus cerasus L.) on kidney morphology and protein expression in rats with diet-induced obesity (DIO). Methods include histological staining and immunohistochemical and Western blot assays. Obese rodents were fed with seed powder (DS) and seed powder plus juice (DJS) of the tart cherry. Results demonstrated that rats fed a high-fat-diet (HFD) showed a significant reduction in renal expression of the pro-inflammatory cytokines interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) following tart cherry supplementation. Furthermore, the study provided evidence that TRP channels, specifically TRP canonical 1 (TRPC1) and TRP melastatin 2 (TRPM2), were significantly upregulated in obese animals (p < 0.05 vs. CHOW rats) and markedly downregulated following tart cherry supplementation (p < 0.05 vs. DIO rats). In conclusion, these TRP proteins offer new insights for identifying targets and biomarkers for developing therapeutic strategies against HFD-induced renal damage, characterized by glomerulosclerosis, fibrosis, and inflammation. Tart cherries supplementation exerted a protective effect on the kidneys by reducing protein oxidation and pro-inflammatory cytokine expression.