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

Yingying Meng1, Cong Yuan1, Jing Zhang1

  • 1Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, PR China; National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China.

Insights

Dietary stearic acid (SA) suppresses pubertal mammary gland development by inhibiting cell proliferation and PI3K/Akt signaling via GPR120 activation. This fatty acid impacts key growth markers in mice and mammary cells.

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Nutritional Science

Background:

  • High-fat diets negatively impact pubertal mammary gland development.
  • Stearic acid (SA) is an 18-carbon saturated fatty acid found in the diet.

Purpose of the Study:

  • To investigate the effects of dietary SA on mammary gland development in pubertal mice.
  • To explore the underlying molecular mechanisms of SA's action.

Main Methods:

  • In vivo studies using pubertal mice supplemented with SA.
  • In vitro studies using mouse mammary epithelial cells (HC11) treated with SA.
  • Analysis of mammary duct development, cell proliferation markers (Cyclin D1, p21, PCNA), G protein-coupled receptor 120 (GPR120) expression, and the PI3K/Akt signaling pathway.
  • GPR120 knockdown using siRNA in vitro.

Main Results:

  • Dietary SA suppressed mammary duct development, reducing terminal end bud (TEB) number and ductal branching in mice.
  • SA decreased the expression of the proliferative marker Cyclin D1 in vivo.
  • SA increased GPR120 expression and inhibited the PI3K/Akt signaling pathway in mouse mammary glands.
  • In vitro, SA suppressed HC11 cell proliferation and altered proliferative marker expression.
  • SA activated GPR120 and inhibited PI3K/Akt signaling in a GPR120-dependent manner.
  • GPR120 knockdown abolished SA's effects on cell proliferation and signaling pathways.

Conclusions:

  • Stearic acid suppresses pubertal mammary gland development in mice.
  • SA inhibits mammary epithelial cell proliferation through GPR120 activation and subsequent PI3K/Akt pathway inhibition.
  • These findings offer insights into how dietary fatty acids regulate mammary gland development.

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