Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouseKarolinska 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..
Karolinska Inst, Ctr Innovat Med, Dept Biosci & Nutr, Huddinge, Sweden.;Karolinska Univ, Hosp Huddinge, Karolinska Inst, Dept Lab Med,Div Clin Chem, Huddinge, Sweden..
Karolinska Univ, Hosp Huddinge, Karolinska Inst, Dept Lab Med,Div Clin Chem, Huddinge, Sweden..
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, Mass Spectrometry Ctr, Dept Chem QOPNA CESAM & ECOMARE, Aveiro, Portugal..
Karolinska Univ, Hosp Huddinge, Karolinska Inst, Dept Lab Med,Div Clin Chem, Huddinge, Sweden..
Karolinska Inst, Ctr Innovat Med, Dept Biosci & Nutr, Huddinge, Sweden.;Univ Houston, Ctr Nucl Receptors & Cell Signalling, Dept Biol & Biochem, Houston, TX USA..
Karolinska Inst, Ctr Innovat Med, Dept Biosci & Nutr, Huddinge, Sweden.;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..
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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
Identifiers
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
Note
QC 20190401
2019-04-012019-04-012022-06-26Bibliographically approved