Conjugated Linoleic Acid (CLA) Mitigates High-Fat Diet (HFD)-Induced Mammary Gland Development Impairment of Pubertal Mice via Regulating CD36 Palmitoylation and Downstream JNK-ERK Pathway.

Conjugated linoleic acid (CLA) is known for antiobesity. However, the role of CLA in regulating high-fat diet (HFD)-impaired pubertal mammary gland development remains undefined. Here, pubertal female mice and HC11 cells were treated with HFD or palmitic acid (PA), supplemented with or without CLA, respectively. We found that CLA prevented impaired mammary gland development in pubertal mice exposed to HFD. In vitro, c9, t11-CLA, but not t10, c12-CLA, promoted PA-suppressed HC11 proliferation, accompanied by hindered CD36 palmitoylation and localization on the plasma membrane. Moreover, c9, t11-CLA reduced the formation of the CD36/Fyn/Lyn complex and inhibited the JNK pathway while activated the ERK pathway in PA-treated HC11. In mechanism, the activation of the JNK pathway and the inhibition of ERK abolished the c9, t11-CLA-stimulated proliferation of PA-treated HC11. In vivo verification, CLA reduced the total and cell membrane CD36 palmitoylation, suppressed the formation of the CD36/FYN/LYN complex, and inhibited the JNK pathway but activated the ERK pathway in the mammary gland of HFD-fed mice. In conclusion, CLA mitigated HFD-impaired mammary gland development of pubertal mice and PA-suppressed HC11 proliferation via CD36 palmitoylation and the downstream JNK-ERK pathway. These data suggested the potential application of CLA in ameliorating obesity-impaired pubertal mammary gland development.