Fabio Novielli

Metabolic syndrome (MetS) is a clinical condition defined by abdominal obesity, insulin resistance, hypertension, and dyslipidaemia, associated with increased cardiovascular risk and type 2 diabetes (T2D). Emerging evidence suggests a role for iron metabolism and ferroptosis in the pathophysiology of MetS and its related complications. This study aimed to explore the association between serum iron levels and clinical, anthropometric, and biochemical parameters in a population with cardiometabolic risk factors. Weongoing treatment for such analysed data from 893 patients attending the Metabolic Disease Unit of the Interdisciplinary Medicine Department at the University of Bari “Aldo Moro”. Patients with MetS, elevated BMI, hypertension, and T2D exhibited significantly lower serum iron levels compared to healthy controls. Serum iron showed a strong inverse correlation with age ( r = − 0.09, p = 0.0061), fasting plasma glucose ( r = − 0.10, p = = .002), and HbA1c ( r = − 0.18, p < 0.0001) in the overall population, while no correlations were found with Framingham Risk Score, triglycerides, waist circumference, and BMI. Conversely, when stratifying by sex, we observed that serum iron was inversely correlated with BMI ( r = − 0.12, p = 0.008) and waist circumference ( r = − 0.12, p = 0.008) in females only. Metabolic dysfunction is associated with reduced serum iron levels, with sex-specific patterns observed in relation to adiposity markers. Elucidating the interplay between iron metabolism, sex hormones, and adipose tissue biology may uncover new targets for personalized treatment strategies for metabolic diseases. Further research is warranted to clarify how modulation of iron homeostasis affects adipose tissue function, particularly in women with obesity and related metabolic disorders. Graphical abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of increased adiposopathy, whose pathogenetic features have been proposed as tumourigenic triggers for colorectal cancer (CRC). We aim to identify specific metabolic signatures involved in CRC development that may be used as non-invasive biomarkers, paving the way for specific and personalized strategies of CRC prevention and early detection. Methods: We retrospectively assessed CRC onset during a time frame of 8 years in a cohort of 1145 out-patients individuals who had previously been evaluated for Metabolic Syndrome. Results: 28 patients developed CRC. No association between CRC development and visceral and general obesity was detected, while baseline fasting plasma glucose (FPG) and non-invasive liver fibrosis scores were significantly higher in patients with CRC, compared to those who did not develop cancer. Liver steatosis and MASLD were more frequently diagnosed in patients who developed CRC compared to no cancer developers. Canonical correlations among metabolic biomarkers were not present in CRC developers, differently from no cancer group. In ROC analysis, FPG and non-invasive scores also showed good sensitivity and specificity in predicting colon cancer. We then calculated ORs for metabolic biomarkers, finding that higher FPG and non-invasive scores were associated with an increased risk of developing CRC. Conclusion: MASLD and increased FPG may play a role in the clinical background of CRC, bringing to light the fascinating possibility of a reversed gut–liver axis communication in the pathogenesis of CRC. Thus, the use of non-invasive scores of fatty liver may be helpful to predict the risk of CRC and serve as novel prognostic factors for prevention and therapeutic strategies.

Background. Gastrointestinal (GI) cancers are one of the most relevant causes of death globally, frequently associated with poor dietary patterns. The Mediterranean Diet (MedDiet) contributes to cancer prevention. To assess adherence to MedDiet, our research group validated a new score, the Chrono Med Diet Score (CMDS), that captures increased visceral adiposity. Methods. We enrolled 401 subjects who underwent an evaluation for metabolic diseases and specific screening procedures according to current guidelines and were asked to answer CMDS. A total of 71 new cancer cases were recorded, including 40 GI and 31 non-gastrointestinal (NON-GI) cancers. Results. We found that CMDS was reduced in subjects who were diagnosed with cancers. Patients who reported a CMDS score of 12 or less had an over three times increased risk of being diagnosed with GI cancers and presented increased waist circumference and triglycerides and reduced HDL cholesterol compared to adherent subjects. Conclusions. Low CMDS values capture the risk for cancer diagnosis, especially for GI cancers. Thus, CMDS, along with waist circumference, can be considered as a bona fide marker for increased risk of cancer, requiring anticipated screening procedures for the detection of premalignant and early stage GI cancers in patients with low adherence to MedDiet.