title: Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.
abstract: Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, Republic of Korea.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors.forename: Sou Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, Republic of Korea.
authors.forename: Sang-Nam
authors.initials: SN
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, Republic of Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, Republic of Korea.
authors.forename: Jeong-Dong
authors.initials: JD
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors.forename: Ji Youn
authors.initials: JY
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Jung
mesh_terms: D002001:Adipose Tissue, Brown / Q000473:pathology; D052436:Adipose Tissue, White / Q000473:pathology*; D000818:Animals; D002478:Cells, Cultured; D002796:Choline Deficiency / Q000150:complications*; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D008066:Lipolysis; D008099:Liver / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000201:enzymology / Q000473:pathology; D012737:Sex Factors; D013737:Testis / Q000201:enzymology / Q000473:pathology; D000071256:Uncoupling Protein 1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D008715:Methionine
keywords: FGF21; Pathology Section; adipose tissue; fatty liver; lipolysis; sex difference