Epidemiological observations, experimental studies and clinical data show that obesity is associated with a higher risk of developing different types of cancer; however, proof of a cause–effect relationship that meets the causality criteria is still lacking. Several data suggest that the adipose organ could be the protagonist in this crosstalk. In particular, the adipose tissue (AT) alterations occurring in obesity parallel some tumour behaviours, such as their theoretically unlimited expandability, infiltration capacity, angiogenesis regulation, local and systemic inflammation and changes to the immunometabolism and secretome. Moreover, AT and cancer share similar morpho-functional units which regulate tissue expansion: the adiponiche and tumour-niche, respectively. Through direct and indirect interactions involving different cellular types and molecular mechanisms, the obesity-altered adiponiche contributes to cancer development, progression, metastasis and chemoresistance. Moreover, modifications to the gut microbiome and circadian rhythm disruption also play important roles. Clinical studies clearly demonstrate that weight loss is associated with a decreased risk of developing obesity-related cancers, matching the reverse-causality criteria and providing a causality correlation between the two variables. Here, we provide an overview of the methodological, epidemiological and pathophysiological aspects, with a special focus on clinical implications for cancer risk and prognosis and potential therapeutic interventions.

Background/Objectives: A disruption of eating habits is related to obesity and obesity-related complications (ORCs), including diabetes and cardiovascular disease. We previously described chrono-nutritional profiles considering the eating habits of patients with severe obesity during the 24 h cycle. Our present study aims to determine, first, whether belonging to a specific eating profile is associated with greater or lesser weight loss in patients with obesity who have undergone bariatric surgery, and second, whether chrono-nutritional profiles are associated with the remission of ORCs after surgery. We also investigated whether there were differences between the original baseline profile and the new profile derived from the 24 h recall on dietary patterns. Methods: The study included 75 patients with obesity who had undergone bariatric surgery and were followed up for a period of 36 ± 11 months. Data were collected from patients’ medical records and telephone interviews. R software (v4.4.0; R Core Team, 2024) was used. Results: Significant weight loss from baseline was observed at follow-up for all profiles (p < 0.0001); however, there were no significant differences in weight loss % among profiles. Using a linear regression model, Profile 3 (characterized by irregular eating patterns) demonstrated less weight loss at follow-up compared to other profiles (p = 0.0487). There was a significant remission of ORCs from baseline to follow-up, but there were no significant differences among profiles. Conclusions: Chrono-nutritional profiles may play a role in weight regulation in patients with severe obesity who are candidates for bariatric surgery. Further studies with a larger sample size are needed.

Background: Multiple symmetric lipomatosis (MSL) is an orphan disease characterized by pathological expansion of lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT) areas, causing severe deformities and compression of vital organs. To date, the only treatment options available are either lifestyle modification or surgical excision/liposuction. Since sex hormones play an important role in adipose tissue (AT) expansion, they may represent an opportunity for pharmacological treatment. Methods: LT and control SAT were collected from eight MSL patients. Both tissues and derived stromal vascular fraction (SVF) were compared in terms of aromatase (hCYP19A1) and 5-α-reductase isoform (hSRD5A1, -2 and -3) mRNA expression. Primary cultures obtained from one MSL patient were exposed to an aromatase inhibitor, 5-α-reductase inhibitor and DL-α-Lipoic Acid and assayed for cell viability, proliferation and adipogenic differentiation. Results: hCYP19A1, hSRD5A1 and hSRD5A3 were expressed in both MSL-affected and MSL-spared tissues at different levels. Cell viability and proliferation of LT-derived SVF cells were slightly increased by treatment with DL-α-Lipoic Acid and the aromatase inhibitor. Adipogenesis was slightly reduced by Finasteride and strongly reduced by Exemestane (more in LT- than in SAT- derived primary cultures). Conclusions: These preliminary results pave the way for the use of aromatase and 5-α-reductase inhibition as a potential pharmacological approach to tackling dysfunctional adipogenesis in MSL. Therefore, the reported study should be interpreted as exploratory and further experiments are recommended in a larger number of patients to validate these promising results.