Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouse.
Marcela González-GranilloLuisa A HelgueroEliana AlvesAmena ArcherChristina SavvaMatteo PedrelliOsman AhmedXidan LiMaria Rosário DominguesPaolo PariniJan-Åke GustafssonMarion Korach-AndréPublished in: Biology of sex differences (2019)
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.
Keyphrases
- insulin resistance
- metabolic syndrome
- adipose tissue
- fatty acid
- high fat diet induced
- weight loss
- type diabetes
- polycystic ovary syndrome
- high fat diet
- postmenopausal women
- weight gain
- skeletal muscle
- uric acid
- cardiovascular risk factors
- bone mineral density
- physical activity
- pregnant women
- electronic health record
- oxidative stress
- deep learning
- big data
- prostate cancer
- genome wide
- body weight
- endothelial cells
- single molecule
- genetic diversity
- high glucose
- data analysis