TY - JOUR
T1 - Hepatic steatosis and steatohepatitis
T2 - a functional meta-analysis of sex-based differences in transcriptomic studies
AU - Català-Senent, José F.
AU - Hidalgo, Marta R.
AU - Berenguer, Marina
AU - Parthasarathy, Gopanandan
AU - Malhi, Harmeet
AU - Malmierca-Merlo, Pablo
AU - de la Iglesia-Vayá, María
AU - García-García, Francisco
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Previous studies have described sex-based differences in the epidemiological and clinical patterns of non-alcoholic fatty liver disease (NAFLD); however, we understand relatively little regarding the underlying molecular mechanisms. Herein, we present the first systematic review and meta-analysis of NAFLD transcriptomic studies to identify sex-based differences in the molecular mechanisms involved during the steatosis (NAFL) and steatohepatitis (NASH) stages of the disease. Methods: Transcriptomic studies in the Gene Expression Omnibus database were systematically reviewed following the PRISMA statement guidelines. For each study, NAFL and NASH in premenopausal women and men were compared using a dual strategy: gene-set analysis and pathway activity analysis. Finally, the functional results of all studies were integrated into a meta-analysis. Results: We reviewed a total of 114 abstracts and analyzed seven studies that included 323 eligible patients. The meta-analyses identified significantly altered molecular mechanisms between premenopausal women and men, including the overrepresentation of genes associated with DNA regulation, vinculin binding, interleukin-2 responses, negative regulation of neuronal death, and the transport of ions and cations in premenopausal women. In men, we discovered the overrepresentation of genes associated with the negative regulation of interleukin-6 and the establishment of planar polarity involved in neural tube closure. Conclusions: Our meta-analysis of transcriptomic data provides a powerful approach to identify sex-based differences in NAFLD. We detected differences in relevant biological functions and molecular terms between premenopausal women and men. Differences in immune responsiveness between men and premenopausal women with NAFLD suggest that women possess a more immune tolerant milieu, while men display an impaired liver regenerative response. Graphical abstract: [Figure not available: see fulltext.].
AB - Background: Previous studies have described sex-based differences in the epidemiological and clinical patterns of non-alcoholic fatty liver disease (NAFLD); however, we understand relatively little regarding the underlying molecular mechanisms. Herein, we present the first systematic review and meta-analysis of NAFLD transcriptomic studies to identify sex-based differences in the molecular mechanisms involved during the steatosis (NAFL) and steatohepatitis (NASH) stages of the disease. Methods: Transcriptomic studies in the Gene Expression Omnibus database were systematically reviewed following the PRISMA statement guidelines. For each study, NAFL and NASH in premenopausal women and men were compared using a dual strategy: gene-set analysis and pathway activity analysis. Finally, the functional results of all studies were integrated into a meta-analysis. Results: We reviewed a total of 114 abstracts and analyzed seven studies that included 323 eligible patients. The meta-analyses identified significantly altered molecular mechanisms between premenopausal women and men, including the overrepresentation of genes associated with DNA regulation, vinculin binding, interleukin-2 responses, negative regulation of neuronal death, and the transport of ions and cations in premenopausal women. In men, we discovered the overrepresentation of genes associated with the negative regulation of interleukin-6 and the establishment of planar polarity involved in neural tube closure. Conclusions: Our meta-analysis of transcriptomic data provides a powerful approach to identify sex-based differences in NAFLD. We detected differences in relevant biological functions and molecular terms between premenopausal women and men. Differences in immune responsiveness between men and premenopausal women with NAFLD suggest that women possess a more immune tolerant milieu, while men display an impaired liver regenerative response. Graphical abstract: [Figure not available: see fulltext.].
KW - Computational biology
KW - Non-alcoholic fatty liver disease
KW - Precision medicine
KW - Sex characteristics
KW - Transcriptome profiling
UR - http://www.scopus.com/inward/record.url?scp=85103397668&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103397668&partnerID=8YFLogxK
U2 - 10.1186/s13293-021-00368-1
DO - 10.1186/s13293-021-00368-1
M3 - Article
C2 - 33766130
AN - SCOPUS:85103397668
SN - 2042-6410
VL - 12
JO - Biology of Sex Differences
JF - Biology of Sex Differences
IS - 1
M1 - 29
ER -