Research Papers: Pathology:

Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease

Yun-Hee Lee, Sou Hyun Kim, Sang-Nam Kim, Hyun-Jung Kwon, Jeong-Dong Kim, Ji Youn Oh and Young-Suk Jung _

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Oncotarget. 2016; 7:46959-46971. https://doi.org/10.18632/oncotarget.10506

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Yun-Hee Lee1, Sou Hyun Kim2, Sang-Nam Kim1, Hyun-Jung Kwon1, Jeong-Dong Kim1, Ji Youn Oh2 and Young-Suk Jung2

1 College of Pharmacy, Yonsei University, Incheon, Republic of Korea

2 College of Pharmacy, Pusan National University, Busan, Republic of Korea

Correspondence to:

Young-Suk Jung, email:

Keywords: sex difference, fatty liver, adipose tissue, lipolysis, FGF21, Pathology Section

Received: March 03, 2016 Accepted: June 30, 2016 Published: July 09, 2016


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.

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PII: 10506