Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice.
Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor- and lipid/lipoprotein metabolism-related gene expression. Interestingly, we found that hepatic steatosis was accompanied by markedly elevated plasma testosterone levels in male ArKO mice but not in female ArKO mice. Plasma lipoprotein profiles exhibited concurrent decreases in LDL- and small dense LDL-triglyceride (TG) levels in male ArKO mice. Moreover, male mice, but not female mice, exhibited marked elevations in androgen receptor (AR), sterol regulatory element-binding protein 1 (SREBP1), and CD36 expression. These results strongly suggest that Cyp19 gene disruption, which induces a sexually dimorphic response and high plasma testosterone levels in male mice, also induces hepatic steatosis.
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
Akiko
A
Amano
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
Yoshitaka
Y
Kondo
Animal Facility, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
Yoshihiro
Y
Noda
Department of Medical Biochemistry, Kobe Pharmaceutical University, Hyogo, 658-8558, Japan.
Mitsuhiro
M
Ohta
Graduate School of Health and Sports Science, Juntendo University, Chiba, 270-1695, Japan.
Noriaki
N
Kawanishi
Graduate School of Health and Sports Science, Juntendo University, Chiba, 270-1695, Japan.
Shuichi
S
Machida
Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan.
Kazuteru
K
Mitsuhashi
Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan.
Takafumi
T
Senmaru
Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan.
Michiaki
M
Fukui
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan.
Osamu
O
Takaoka
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan.
Taisuke
T
Mori
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan.
Jo
J
Kitawaki
Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, 783-8505, Japan.
Masafumi
M
Ono
Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, 783-8505, Japan.
Toshiji
T
Saibara
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan; Bio-Response Informatics, Kyoto, 612-8016, Japan.
Hiroshi
H
Obayashi
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan. Electronic address: ishigami@tmig.or.jp.
Akihito
A
Ishigami
D000818:Animals; D001141:Aromatase / Q000032:analysis / Q000235:genetics*; D018955:CD36 Antigens / Q000032:analysis / Q000235:genetics; D004967:Estrogens / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000032:analysis / Q000235:genetics; D013739:Testosterone / Q000097:blood* / Q000378:metabolism; D015854:Up-Regulation
D018955:CD36 Antigens; D004967:Estrogens; D008074:Lipoproteins; D011944:Receptors, Androgen; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D013739:Testosterone; D001141:Aromatase
Aromatase; Cyp19; PPARα; SREBP1; Steatosis; Testosterone