Alessandro Antonioli

Bone is a dynamic specialized connective tissue that undergoes continuous remodeling to preserve its health. Bone health is influenced throughout life by a combination of genetic, hormonal, and environmental factors, as well as physical activity and diet. This study aims to evaluate the effects of diets with different fat content on the femurs of mice fed for 16 or 20 weeks on a normal diet (ND16w and ND20w) or a Western diet (WD16w and WD20w) and for 20 weeks with their combinations on a ketogenic diet (KD) (WD + ND20w, ND + KD20w, and WD + KD20w). Micro-CT analysis on femoral cancellous bone revealed a non-significant trend toward decreased bone volume fraction (BV/TV) and trabecular thickness in mice fed a combined WD + KD20w compared to WD20w. Cortical bone thickness was significantly lower in mice fed WD16w and WD20w compared to those fed ND16w and ND20w (p = 0.049 and p = 0.039, respectively), in mice fed WD20w Ct.Th increased compared to WD + ND20w (p = 0.024) and a strong decrease is evident when comparing WD + ND20w to WD + KD20w (p < 0.0004). Consistently, histological analysis revealed that the number of osteoclasts per bone perimeter on cancellous bone increases compared with ND20w with ND + KD20w (p = 0.007) and WD + ND20w with ND + KD20w (p = 0.0006). In addition, a decrease in osteoblasts was observed (p < 0.041) in cortical bone, comparing ND20w with ND + KD20w; this suggests that the KD may have differential effects depending on the baseline condition. Osteocyte numbers did not significantly change when comparing the different treatments. Masson staining supports micro-CT results on both cortical and cancellous bone. In conclusion, transition from a high-fat diet to a normal diet may partially restore cortical bone health, whereas transition to a ketogenic diet exerts a trend toward additional detrimental effects on trabecular bone.

Background: Oxidative stress and chronic inflammation contribute to the pathogenesis of obesity and type 2 diabetes (T2D), yet the effects of dietary interventions on endogenous antioxidant defences remain poorly defined. This is a non-randomized study evaluates the effects of very-low-energy ketogenic therapy (VLEKT), compared with a Mediterranean diet (MedD) and a control group, on antioxidants, metabolic, and inflammatory markers. Materials and Methods: Thirty adults with obesity and T2D were assigned to VLEKT (n = 10), MedD (n = 10), or control (n = 10) for 90 days. Metabolic parameters, inflammatory cytokines, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were assessed. Longitudinal changes were analyzed using linear mixed models. Results: VLEKT exhibited significant reductions in body weight, fat mass, HbA1c, and HOMA-IR. SOD activity increased in the VLEKT group, whereas no significant changes were observed in MedD. Changes in SOD were inversely associated with changes in HOMA-IR. GPx showed a less consistent response pattern, while inflammatory markers did not differ between groups. Conclusions: VLEKT was associated with substantial metabolic improvement accompanied by a selective modulation of antioxidant enzyme activity. The increase in SOD activity and its association with HOMA-IR suggest a link between metabolic and redox adaptations in subjects with obesity and T2D.

Fructose, a key component of modern diets, is closely linked to the growing prevalence of pediatric obesity and metabolic alterations. Although numerous studies highlight its systemic consequences, including altered carbohydrate and lipid metabolism and increased cardiovascular risk, the direct impact of fructose, particularly its role in modulating mucin composition, a key determinant of the mucosal barrier, remains poorly explored. This study investigated whether fructose supplementation modifies high-fat diet (HFD)-induced changes in duodenal mucin production and whether these effects vary depending on age in animals. To this end, young and adult mice were fed a normal diet (ND), HFD, or an HFD supplemented with 30% fructose (w/v) in drinking water (HFD+Fru) for 16 weeks. Brunner’s glands and villus goblet cells were then analyzed using conventional histochemistry and a panel of lectins to evaluate possible alterations in intestinal mucus glycosylation. Results showed that both HFD and HFD+Fru significantly increased body weight. In young mice, HFD+Fru induced a compensatory mucosal phenotype characterized by increased villus PAS (Periodic Acid–Schiff) reactivity (2% vs. ND), elevated sialylated mucin secretion rate (SSR) in Brunner’s glands (25% vs. ND) and villi (17% vs. ND), and higher SNA (up to 46% vs. ND) and PNA (up to 39% vs. ND) in villus goblet cells. In contrast, adult mice receiving HFD+Fru exhibited a maladaptive response, characterized by a reduction in villus PAS-positive mucins (6% vs. ND), decreased villus SSR (5% vs. ND), diminished sialylation (up to 43% SNA vs. ND) and GlcNAc (up to 50% reduction in WGA vs. ND) in villus goblet cells, and marked loss of fucosylation in Brunner’s glands (81% vs. ND) and villus goblet cells (66% vs. ND). These results reveal that fructose-enriched HFD remodels duodenal mucin O-glycosylation in an age-dependent manner, suggesting that while young mice exhibit transient adaptive responses, prolonged exposure can deplete these mechanisms, leading to a compromised adult epithelial barrier. This age-specific vulnerability may significantly contribute to the pathogenesis of diet-related intestinal disorders and obesity-related complications in later life, highlighting the need for early dietary interventions.

Obesity is an alarming public health problem. Tailored nutritional therapy is advisable since emerging evidence on complex cross-talks among multifactorial agents. In this picture, the gut microbiota is highly individualized and intricately dependent on dietary patterns, with implications for obesity management. Most of the papers on the topic are observational and often conflicting. This review aimed to systematically organize the body of evidence on microbiota deriving from dietary trials in adult obesity giving the most certain phylogenetic, and metabolomic signatures in relation to both the host metabolism and phenotype changes published until now. We retrieved 18 randomized control trials on 1385 subjects with obesity who underwent several dietary interventions, including standard diet and healthy dietary regimens. Some phyla and species were more related to diets rich in fibers and others to healthy diets. Weight loss, metabolism improvements, inflammatory markers decrease were specifically related to different microorganisms or functions. The Prevotella/Bacteroides ratio was one of the most reported predictors. People with the burden of obesity comorbidities had the most significant taxonomic changes in parallel with a general improvement. These data emphasize the possibility of using symbiotic approaches involving tailored diets, microbiota characteristics, and maybe drugs to treat obesity and metabolic disorders. We encourage Authors to search for specific phylogenetic associations beyond a too generally reported Firmicutes/Bacteroides ratio.