Serum metabolomic profiling unveils distinct sex-related metabolic patterns in NAFLD

Charalambos Fotakis; Ioanna-Panagiota Kalafati; Athina I Amanatidou; Vasiliki Andreou; Manolis Matzapetakis; Maria Kafyra; Iraklis Varlamis; Maria Zervou; George V Dedoussis

doi:10.3389/fendo.2023.1230457

Serum metabolomic profiling unveils distinct sex-related metabolic patterns in NAFLD

Front Endocrinol (Lausanne). 2023 Oct 3:14:1230457. doi: 10.3389/fendo.2023.1230457. eCollection 2023.

Authors

Charalambos Fotakis¹, Ioanna-Panagiota Kalafati², Athina I Amanatidou², Vasiliki Andreou¹, Manolis Matzapetakis¹, Maria Kafyra², Iraklis Varlamis³, Maria Zervou¹, George V Dedoussis²

Affiliations

¹ Institute of Chemical Biology, National Hellenic Research Foundation, Athens, Greece.
² Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University of Athens, Athens, Greece.
³ Department of Informatics and Telematics, Harokopio University of Athens, Athens, Greece.

Abstract

Objective: Obesity poses an increased risk for the onset of Nonalcoholic fatty liver disease (NAFLD). The influence of other factors, such as sex in the incidence and severity of this liver disease has not yet been fully elucidated. Thus, we aimed to identify the NAFLD serum metabolic signatures associated with sex in normal, overweight and obese patients and to associate the metabolite fluctuations across the increasing liver steatosis stages.

Methods and results: Using nuclear magnetic resonance (NMR) serum samples of 210 NAFLD cases and control individuals diagnosed with liver U/S, our untargeted metabolomics enquiry provided a sex distinct metabolic bouquet. Increased levels of alanine, histidine and tyrosine are associated with severity of NAFLD in both men and women. Moreover, higher serum concentrations of valine, aspartic acid and mannose were positively associated with the progression of NAFLD among the male subjects, while a negative association was observed with the levels of creatine, phosphorylcholine and acetic acid. On the other hand, glucose was positively associated with the progression of NAFLD among the female subjects, while levels of threonine were negatively related. Fluctuations in ketone bodies acetoacetate and acetone were also observed among the female subjects probing a significant reduction in the circulatory levels of the former in NAFLD cases. A complex glycine response to hepatic steatosis of the female subjects deserves further investigation.

Conclusion: Results of this study aspire to address the paucity of data on sex differences regarding NAFLD pathogenesis. Targeted circulatory metabolome measurements could be used as diagnostic markers for the distinct stages of NAFLD in each sex and eventually aid in the development of novel sex-related therapeutic options.

Keywords: NAFLD; NMR metabolomics; adolescent obesity; amino acids; glycine neurotransmitter; ketone bodies; serum metabolite markers; sex.

MeSH terms

Female
Humans
Male
Metabolome
Metabolomics / methods
Non-alcoholic Fatty Liver Disease* / complications
Obesity / metabolism

Grants and funding

This project was funded by the European Union and Greek national funds, through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH-CREATE-INNOVATE (project code: T2EDK-03044).