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Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouse
Karolinska Inst, Ctr Endocrinol Metab & Diabet, Dept Med, Metab & Mol Nutr Unit, S-14186 Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Dept Med, Karolinska Inst, AstraZeneca Integrated Cardio Metab Ctr, C2-94, S-14186 Stockholm, Sweden..
Univ Aveiro, Inst Biomed, Dept Med Sci, Aveiro, Portugal..
Univ Aveiro, Mass Spectrometry Ctr, Dept Chem QOPNA CESAM & ECOMARE, Aveiro, Portugal..ORCID iD: 0000-0001-5396-6536
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Cellular and Clinical Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Ctr Innovat Med, Dept Biosci & Nutr, Huddinge, Sweden.
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2019 (English)In: Biology of Sex Differences, ISSN 2042-6410, Vol. 10, article id 11Article in journal (Refereed) Published
Abstract [en]

The response to overfeeding is sex dependent, and metabolic syndrome is more likely associated to obesity in men or postmenopausal women than in young fertile women. We hypothesized that obesity-induced metabolic syndrome is sex dependent due to a sex-specific regulation of the fatty acid (FA) synthesis pathways in liver and white adipose depots. We aimed to identify distinctive molecular signatures between sexes using a lipidomics approach to characterize lipid species in liver, perigonadal adipose tissue, and inguinal adipose tissue and correlate them to the physiopathological responses observed. Males had less total fat but lower subcutaneous on visceral fat ratio together with higher liver weight and higher liver and serum triglyceride (TG) levels. Males were insulin resistant compared to females. Fatty acid (FA) and TG profiles differed between sexes in both fat pads, with longer chain FAs and TGs in males compared to that in females. Remarkably, hepatic phospholipid composition was sex dependent with more abundant lipotoxic FAs in males than in females. This may contribute to the sexual dimorphism in response to obesity towards more metaflammation in males. Our work presents an exhaustive novel description of a sex-specific lipid signature in the pathophysiology of metabolic disorders associated with obesity in ob/ob mice. These data could settle the basis for future pharmacological treatment in obesity.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 10, article id 11
Keywords [en]
Lipidomics, Fatty acids, Obesity, Metabolic syndrome, Sex
National Category
Medical Biotechnology
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URN: urn:nbn:se:kth:diva-246258DOI: 10.1186/s13293-019-0225-yISI: 000459861300001PubMedID: 30808418Scopus ID: 2-s2.0-85062477915OAI: oai:DiVA.org:kth-246258DiVA, id: diva2:1300919
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QC 20190401

Available from: 2019-04-01 Created: 2019-04-01 Last updated: 2019-04-04Bibliographically approved

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Archer, Amena

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