Diet-induced obesity disrupts ductal development in the mammary glands of nonpregnant mice.
Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin.
Kamikawa
Akihiro
A
Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Ichii
Osamu
O
Yamaji
Daisuke
D
Imao
Takeshi
T
Suzuki
Chiharu
C
Okamatsu-Ogura
Yuko
Y
Terao
Akira
A
Kon
Yasuhiro
Y
Kimura
Kazuhiro
K
D052242:Adiponectin / Q000097:blood; D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D054411:Receptors, Leptin / Q000378:metabolism*
D052242:Adiponectin; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D054411:Receptors, Leptin