Stearic acid suppresses mammary gland development by inhibiting PI3K/Akt signaling pathway through GPR120 in pubertal mice

Journal Article · Sat Sep 09 04:00:00 EDT 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.07.075· OSTI ID:22719070

Meng, Yingying; Yuan, Cong; Zhang, Jing; Zhang, Fenglin; Fu, Qin; Zhu, Xiaotong; Shu, Gang; Wang, Lina; Gao, Ping; Xi, Qianyun; Sun, Jiajie; Zhang, Yongliang; Jiang, Qingyan ^[1]; Wang, Songbo ^[1]

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1. Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642 (China)

It has been demonstrated that dietary high fat diet negatively affects the pubertal mammary gland development. The aim of the present study was to investigate the effects of stearic acid (SA), an 18-carbon chain saturated fatty acid, on mammary gland development in pubertal mice and to explore the underlying mechanism. Our results demonstrated that dietary supplementation of 2% SA suppressed mammary duct development, with significant reduction of terminal end bud (TEB) number and ductal branch. In accord, the expression of proliferative marker Cyclin D1 was markedly decreased by dietary SA. Furthermore, dietary SA led to increase of G protein-coupled receptor 120 (GPR120) expression and inhibition of PI3K/Akt signaling pathway in mammary gland of pubertal mice. In good agreement with the in vivo findings, the in vitro results showed that 40 μM SA significantly suppressed proliferation of mouse mammary epithelial cell HC11 by regulating mRNA and/or protein expression of proliferative markers such as Cyclin D1/3, p21, and PCNA. Meanwhile, SA activated GPR120 and inhibited PI3K/Akt signaling pathway in a GPR120-dependent manner. In addition, SA-induced inhibition of PI3K/Akt signaling pathway, suppression of HC11 proliferation, and alteration of proliferative markers expression were abolished by knockdown of GPR120 with siRNA. Collectively, these findings showed that SA suppressed mammary gland development of pubertal mice, which was coincident with the SA-inhibited HC11 proliferation, and was associated with inhibition of PI3K/Akt signaling pathway through activation of GPR120. These data provided new insights into the regulation of mammary gland development by dietary fatty acids. - Highlights: • Dietary supplementation of 2% SA suppressed mammary duct growth in pubertal mice. • SA inhibited HC11 proliferation by regulating expression of proliferative markers. • SA enhanced GPR120 and inhibited PI3K/Akt in mice mammary gland and HC11 cells. • Knockdown of GPR120 eliminated SA-suppressed PI3K/Akt and HC11 proliferation.

• OSTI ID: 22719070
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 491; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIGENS
GTP-ASES
IN VITRO
IN VIVO
INHIBITION
MAMMARY GLANDS
MESSENGER-RNA
MICE
MONOCLINIC LATTICES
OCTADECANOIC ACID
PHOSPHOTRANSFERASES
RECEPTORS