| First Author | Herrera-Marcos LV | Year | 2020 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 318 |
| Issue | 2 | Pages | E249-E261 |
| PubMed ID | 31846369 | Mgi Jnum | J:286283 |
| Mgi Id | MGI:6400909 | Doi | 10.1152/ajpendo.00199.2019 |
| Citation | Herrera-Marcos LV, et al. (2020) Pgc1a is responsible for the sex differences in hepatic Cidec/Fsp27beta mRNA expression in hepatic steatosis of mice fed a Western diet. Am J Physiol Endocrinol Metab 318(2):E249-E261 |
| abstractText | Hepatic fat-specific protein 27 [cell death-inducing DNA fragmentation effector protein C (Cidec)/Fsp27] 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 (Apoe)-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 Cidec/Fsp27 mRNA expression. Dietary cholesterol increased hepatic Cidec/Fsp27beta 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 Cidec/Fsp27beta 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 (Ldlr)-deficient mice. Incubation with estradiol resulted in decreased Cidec/Fsp27beta 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-gamma coactivator 1-alpha (Pgc1a), suppressed by ovariectomy, and the values were significantly and inversely associated with those of Cidec/Fsp27beta. When Pgc1a-deficient mice were used, the sex differences in Cidec/Fsp27beta expression disappeared. Therefore, hepatic Cidec/Fsp27beta expression has a complex regulation influenced by diet and sex hormonal milieu. The mRNA sex differences are controlled by Pgc1a. |
