Metabolic Assessment of Visceral Adipose Tissue in Patients With Gastric Cancer: An Exploratory Analysis

Visceral adipose tissue (VAT) plays a key role in metabolic and inflammatory regulation and has increasingly been associated with cancer prognosis. Reduced VAT index, along with higher VAT radiodensity and glucose uptake, has been linked to poor outcomes in cancer patients. However, it remains unclear if these alterations result from lipolysis, systemic or tissue inflammation, or adipose tissue beiging/browning. This cross-sectional study aimed to characterize the metabolic profile of VAT in patients with gastric cancer (GC) by integrating imaging-based metabolic assessment with gene expression analysis. This study analyzed a subgroup of 36 patients with histologically confirmed gastric adenocarcinoma treated at the Clinics Hospital of the University of Campinas (HC-UNICAMP). All patients underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). PET-derived metabolic activity of VAT was quantified using the mean standardized uptake value (SUVmean). VAT gene expression was evaluated using the nCounter system (Elements panel), targeting genes associated with adipocyte browning and differentiation, including UCP1, PPARGC1A, PRDM16, CIDEA, DIO2, TMEM26, CD137, TBX1, ZIC1, and LHX8. Clinical, nutritional, and inflammatory data were collected, stored and managed using REDCap. Statistical analyses were performed with Jamovi software (v.2.3.28). The study was approved by the Institutional Review Board (CAAE: 76237023.0.0000.5404). Results: Patients were stratified according to VAT radiodensity into low- and high-radiodensity groups based on the median value (16 and 20 patients, respectively). No significant differences were observed between groups regarding demographic or tumor-related characteristics. The high-radiodensity group exhibited a distinct anthropometric and body composition profile, characterized by lower body mass index, smaller waist circumference, and a lower visceral obesity. This group also presented significantly lower visceral and subcutaneous adipose tissue areas and indices, along with higher attenuation of both VAT (p < 0.001) and SAT (p = 0.003). SUVmean increased in the high-radiodensity group (p < 0.001). Gene expression analysis revealed no major differences between groups with low and high VAT 18F-FDG uptake, except for reduced DIO2 expression in the high-uptake group, suggesting attenuated local thyroid hormone–mediated thermogenic signalling. A trend toward higher PPARGC1A expression was observed in the high-uptake group, possibly reflecting early beige adipocyte differentiation, although canonical thermogenic and beige adipocyte markers remained unchanged. No significant differences were observed in systemic inflammatory markers between groups. Patients with lower VAT radiodensity demonstrated greater insulin sensitivity. In GC patients, high VAT radiodensity and glucose uptake were associated with reduced adipose tissue mass and a distinct metabolic profile, without evidence of systemic inflammation or established adipose tissue browning. These findings suggest that elevated VAT glucose uptake may reflect an early or heterogeneous metabolic response related to cancer-associated alterations rather than active thermogenic remodeling. Further studies with larger cohorts are warranted to better elucidate the underlying mechanisms and clinical relevance of VAT metabolic changes in gastric cancer.