Pgc1a is responsible for the sex differences in hepatic Cidec/Fsp27β mRNA expression in hepatic steatosis of mice fed a Western diet

Hepatic fat-specific protein 27 [cell death-inducing DNA fragmentation effector protein C ( )/ ] mRNA levels have been associated with hepatic lipid droplet extent under certain circumstances. To address its hepatic expression under different dietary conditions and in both sexes, apolipoprotein E (...

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Published in:American journal of physiology: endocrinology and metabolism 2020-02, Vol.318 (2), p.E249-E261
Main Authors: Herrera-Marcos, Luis V, Sancho-Knapik, Sara, Gabás-Rivera, Clara, Barranquero, Cristina, Gascón, Sonia, Romanos, Eduardo, Martínez-Beamonte, Roberto, Navarro, María A, Surra, Joaquín C, Arnal, Carmen, García-de-Jalón, José A, Rodríguez-Yoldi, María J, Tena-Sempere, Manuel, Sánchez-Ramos, Cristina, Monsalve, María, Osada, Jesús
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cholesterol, Dietary - pharmacology
Diet, Western - adverse effects
Female
Lipid Droplets - metabolism
Liver - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Non-alcoholic Fatty Liver Disease - genetics
Non-alcoholic Fatty Liver Disease - metabolism
Orchiectomy
Ovariectomy
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
Proteins - genetics
Receptors, LDL - genetics
Receptors, LDL - metabolism
RNA, Messenger - biosynthesis
Sex Characteristics
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Summary:Hepatic fat-specific protein 27 [cell death-inducing DNA fragmentation effector protein C ( )/ ] mRNA levels have been associated with hepatic lipid droplet extent under certain circumstances. To address its hepatic expression under different dietary conditions and in both sexes, apolipoprotein E ( ) deficient mice were subjected to different experimental conditions for 11 wk to test the influence of cholesterol, Western diet, squalene, oleanolic acid, sex, and surgical castration on mRNA expression. Dietary cholesterol increased hepatic expression, an effect that was suppressed when cholesterol was combined with saturated fat as represented by Western diet feeding. Using the latter diet, neither oleanolic acid nor squalene modified its expression. Females showed lower levels of hepatic expression than males when they were fed Western diets, a result that was translated into a lesser amount of CIDEC/FSP27 protein in lipid droplets and microsomes. This was also confirmed in low-density lipoprotein receptor ( )-deficient mice. Incubation with estradiol resulted in decreased expression in AML12 cells. Whereas male surgical castration did not modify the expression, ovariectomized females did show increased levels compared with control females. Females also showed increased expression of peroxisome proliferator-activated receptor-γ coactivator 1-α ( ), suppressed by ovariectomy, and the values were significantly and inversely associated with those of . When -deficient mice were used, the sex differences in expression disappeared. Therefore, hepatic expression has a complex regulation influenced by diet and sex hormonal milieu. The mRNA sex differences are controlled by .
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00199.2019