The Effect of Sex and Obesity on the Gene Expression of Lipid Flippases in Adipose Tissue

Abstract

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.

Variation in responses to incretin therapy: Modifiable and non-modifiable factors

“…In humans, dietary related alterations in hepatocyte membrane composition, including an increase in phosphatidylethanolamines, have been found to contribute to metabolic-associated fatty liver disease through mitochondrial dysfunction causing the production of ROS, lipid accumulation and loss of insulin sensitivity (Shama et al, 2023). Additionally, in obese humans, visceral fat deposits accumulate where the membrane composition regulating protein ATB8B1 (or flippase) is upregulated (Motahari-Rad et al, 2022). These studies all indicate that diet can influence the make-up of cell membranes and thus, we hypothesise that it may have a potential direct regulatory impact on incretin receptor function in target cells.…”

Multiomics Picture of Obesity in Young Adults

“…This enzyme is involved in the transport of phospholipids across cellular membranes. In patients with obesity, there was an increased expression of the ATP8A1 gene in visceral adipose tissue [44]. The CDK6 gene (cyclin-dependent kinase 6, Q00534) regulates biological pathways associated with the cell cycle.…”