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

Hanieh Motahari-Rad, Alba Subiri, Rocio Soler, Luis Ocaña, Juan Alcaide, Jorge Rodríguez-Capitan, Veronica Buil, Hamid El Azzouzi, Almudena Ortega-Gomez, Rosa Bernal-Lopez, Maria Insenser*, Francisco J. Tinahones, Mora Murri

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number3878
Pages (from-to)1-14
Number of pages14
JournalJournal of Clinical Medicine
Volume11
Issue number13
DOIs
Publication statusPublished - 4 Jul 2022

Bibliographical note

Funding Information:
Funding: H.M.-R. was awarded a scholarship by the Ministry of Science, Research, and Technology of the Islamic Republic of Iran. This work was supported by Miguel Servet I program (CP17/00133) and by PI18/01160 and PI19/00507 from ISCIII, Spanish Ministry of Science and Innovation, UMA18-FEDERJA-285 co-funded by Malaga University, Junta de Andalucıa and FEDER funds, CB06/03/0018 and PI-0297-2018, and co-funded by FEDER funds and Consejerıa de Salud y Familia, Junta de An-dalucıa, Spain. M Rosa Bernal-Lopez was supported by “Miguel Servet Type II” program (CPII/00014) from the ISCIII-Madrid (Spain), cofunded by the Fondo Europeo de Desarrollo Regional-FEDER and “Nicolas Monardes” program, (C1-0005-2020) supported by Consejeria de Salud, Junta de Andalucía.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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