Mitochondrial respiration in white adipose tissue is dependent on body mass index and tissue location in patients undergoing oncological or parietal digestive surgery

Abstract

Adipose tissue (AT), is a major endocrine organ that plays a key role in health and disease. However, adipose dysfunctions, especially altered energy metabolism, have been under-investigated as white adipocytes have relatively low mitochondrial density. Nevertheless, recent studies suggest that mitochondria could play a major role in AT disorders and that AT mitochondrial activity could depend on adiposity level and location. This clinical study aimed to evaluate mitochondrial respiration and metabolism in human visceral (vAT) and subcutaneous (scAT) AT and their relationship with body mass index (BMI). This clinical study enrolled 67 patients (30 females/37 males) scheduled for digestive surgery without chemotherapy and parietal infection. BMI ranged from 15.4 to 51.9 kg·m⁻² and body composition was estimated by computed tomographic images. Mitochondrial respiration was measured in situ in digitonin-permeabilized AT using high-resolution respirometry and a substrate/inhibitor titration approach. Protein levels of mitochondrial and lipid metabolism key elements were evaluated by Western blot. Maximal mitochondrial respiration correlated negatively with BMI (p < .01) and AT area (p < .001) regardless of the anatomical location. However, oxidative phosphorylation respiration was significantly higher in vAT (2.22 ± 0.15 pmol·sec⁻¹·mg⁻¹) than scAT (1.79 ± 0.17 pmol·sec⁻¹·mg⁻¹) (p < 0.001). In line with oxygraphy results, there were higher levels of mitochondrial respiratory chain complexes in low-BMI patients and vAT. Mitochondrial respiration decreased with increasing BMI in both scAT and vAT, without sex-associated difference. Mitochondrial respiration appeared to be higher in vAT than scAT. These differences were both qualitative and quantitative. Clinical Trials Registration IDNCT05417581.