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Molecular mechanisms behind obesity and sex-related effects in adipose tissue remain elusive. During adipocyte expansion, adipocytes undergo drastic remodelling of lipid membrane compositions. Lipid flippases catalyse phospholipid translocation from exoplasmic to the cytoplasmic leaflet of membranes. The present study aimed to analyse the effect of sex, obesity, and their interactions on the gene expression of two lipid flippases—ATP8A1 and ATP8B1—and their possible microRNA (miR) modulators in visceral adipose tissue (VAT). In total, 12 normal-weight subjects (5 premenopausal women and 7 men) and 13 morbidly obese patients (7 premenopausal women and 6 men) were submitted to surgery, and VAT samples were obtained. Gene expression levels of ATP8A1, ATP8B1, miR-548b-5p, and miR-4643 were measured in VAT. Our results showed a marked influence of obesity on VAT ATP8A1 and ATP8B1, although the effects of obesity were stronger in men for ATP8A1. Both genes positively correlated with obesity and metabolic markers. Furthermore, ATP8B1 was positively associated with miR-548b-5p and negatively associated with miR-4643. Both miRs were also affected by sex. Thus, lipid flippases are altered by obesity in VAT in a sex-specific manner. Our study provides a better understanding of the sex-specific molecular mechanisms underlying obesity, which may contribute to the development of sex-based precision medicine.

CONTEXT: The prevalence of obesity and hypertriglyceridemia is an alarming worldwide health issue. Mitochondria play a central role in these disorders as they control cell metabolism. OBJECTIVE: The aim of the present study was to characterize mitochondrial homeostasis in subcutaneous and visceral adipose tissue (SAT and VAT) in grade III obese patients with and without hypertriglyceridemia. Moreover, this study presents the evaluation of mitochondrial fitness as a marker for hypertriglyceridemia improvement. PATIENTS: Eight control and 12 hypertriglyceridemic (HTG) grade III obese subjects undergoing bariatric surgery were included. MAIN OUTCOME MEASURES: Anthropometric and biochemical data were obtained before and 3 months after surgery. Mitochondrial homeostasis was evaluated by mitochondrial DNA (mtDNA), gene expression and protein abundance in SAT and VAT. RESULTS: Mitophagy-related gene expression was increased in HTG SAT and VAT, while mitochondrial marker gene expression and mtDNA were decreased, indicating an altered mitochondrial homeostasis in HTG. Mitophagy protein abundance was increased in VAT of those subjects that did not improve their levels of triglycerides after bariatric surgery, whereas mitochondrial protein was decreased in the same tissue. Indeed, triglyceride levels positively correlated with mitophagy-related genes and negatively with mitochondrial content markers. Moreover, mitochondria content and mitophagy markers seem to be significant predictors of hypertriglyceridemia and hypertriglyceridemia remission. CONCLUSIONS: Mitochondrial homeostasis of adipose tissue is altered in hypertriglyceridemic patients. At the protein level, mitochondria content and mitophagy are potential markers of hypertriglyceridemia remission in obese patients after bariatric surgery. These results may contribute to the implementation of a clinical approach for personalized medicine.