Sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Silva Gasparin, Fabiana Rodrigues^1,2  Carreno, Fernando Olinto^1,2  Mewes, Juliana Moraes^1,2  Gilglioni, Eduardo Hideo^1,2  Salgueiro Pagadigorria, Clairce Luzia³  Marcal Natali, Maria Raquel⁴  Utsunomiya, Karina Sayuri^1,2  Constantin, Rodrigo Polimeni^1,2  Ouchida, Amanda Tomie⁵  Curti, Carlos⁵  Gaemers, Ingrid C.⁶  Johannes Oude Elferink, Ronald Petrus⁶  Constantin, Jorgete^1,2  Ishii-Iwamoto, Emy Luiza^1,2 

[1] Univ Maringa, Dept Biochem, Lab Biol Oxidat, BR-87020900 Maringa, Parana, Brazil

[2] Univ Maringa, Lab Expt Steatosis, BR-87020900 Maringa, Parana, Brazil

[3] Univ Maringa, Dept Physiol Sci, Maringa, Parana, Brazil

[4] Univ Maringa, Dept Morphophysiol Sci, Maringa, Parana, Brazil

[5] Univ Sao Paulo, Lab Bioenerget, Fac Pharmaceut Sci, Sao Paulo, Brazil

[6] Univ Amsterdam, Acad Med Ctr, Tytgat Inst Liver & Intestinal Res, Amsterdam, Netherlands

关键词: FGF21;    Sex dimorphism;    Western diet;    Hepatic steatosis;    Adipose tissue;    Oxidative stress;   

DOI  :  10.1016/j.bbadis.2018.04.004

来源: Elsevier

【 摘 要 】

The present study was planned to improve our understanding about sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Female (FCaf) and male (MCaf) mice fed a cafeteria diet had similar body weight gain and adiposity index, but FCaf had a more extensive steatosis than MCaf. FCaf livers exhibited a higher non-alcoholic fatty liver disease activity score, elevated lipid percentage area (+ 34%) in Sudan III staining and increased TG content (+ 25%) compared to MCaf. Steatosis in FCaf was not correlated with changes in the transcript levels of lipid metabolism-related genes, but a reduced VLDL release rate was observed. Signs of oxidative stress were found in FCaf livers, as elevated malondialdehyde content (+ 110%), reduced catalase activity (- 36%) and increased Nrf2 and Hif1 a mRNA expression compared to MCaf. Interestingly, fibroblast growth factor 21 (Fgf21) mRNA expression was found to be exclusively induced in MCaf, which also exhibited higher FGF21 serum levels (+ 416%) and hepatic protein abundance (+ 163%) than FCaf. Moreover, cafeteria diet increased Fgfr1, Fsp27 and Ucp1 mRNA expression in brown adipose tissue of males (MCaf), but not females (FCaf). FGF21 hepatic production by male mice seems to be part of a complex network of responses to the nutritional stress of the cafeteria diet, probably related to the unfolded protein response activation. Although aimed at the restoration of hepatic metabolic homeostasis, the branch involving Fgf21 upregulation seems to be impaired in females, rendering them incapable of reducing the hepatic lipid content and cellular oxidative stress.

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