Open AccessLipotoxicity suppresses the synthesis of growth hormone in pituitary somatotrophs via endoplasmic reticulum stress
Author(s) -
Gong Ying,
Yang Jianmei,
Wei Shuoshuo,
Yang Rui,
Gao Ling,
Shao Shanshan,
Zhao Jiajun
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16532
Subject(s) - lipotoxicity , medicine , endocrinology , unfolded protein response , endoplasmic reticulum , somatotropic cell , chop , biology , chemistry , pituitary gland , hormone , microbiology and biotechnology , insulin resistance , insulin
Lipotoxicity has been shown to cause dysfunction of many organs and tissues. However, it is unclear whether lipotoxicity is harmful to the somatotrophs, a kind of cell that synthesize growth hormone (GH) in the pituitary. In this study, we performed an epidemiological study, serum levels of triglyceride (TG) and GH showed a negative correlation, even after adjustment for potential confounders. In an animal study, male Sprague‐Dawley rats were fed a high‐fat diet (HFD) or a control diet for 28 weeks. HFD rats showed impaired GH synthesis, resulting in a decrease in circulating GH levels. The expression of pituitary Pit‐1, a key transcription factor of GH, was inhibited. We found that the inositol‐requiring enzyme 1α (IRE1α) pathway of endoplasmic reticulum (ER) stress was triggered in HFD rat pituitary glands and palmitic acid‐treated GH3 cells, respectively. On the contrary, applying 4‐phenyl butyric acid (4‐PBA) to alleviate ER stress or 4µ8c to specifically block the IRE1α pathway attenuated the impairment of both Pit‐1 and GH expression. In conclusion, we demonstrated that lipotoxicity directly inhibits the synthesis of GH, probably by reducing Pit‐1 expression. The IRE1α signaling pathway of ER stress may play an important role in this process.