AUTHOR=Feng Xu , Xiao Ye , Guo Qi , Peng Hui , Zhou Hai-Yan , Wang Jian-Ping , Xia Zhu-Ying 

TITLE=Parathyroid hormone alleviates non-alcoholic liver steatosis via activating the hepatic cAMP/PKA/CREB pathway

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.899731

DOI=10.3389/fendo.2022.899731

ISSN=1664-2392

ABSTRACT=<p>Non-alcoholic fatty liver disease (NAFLD), hallmarked by liver steatosis, is becoming a global concern, but effective and safe drugs for NAFLD are still lacking at present. Parathyroid hormone (PTH), the only FDA-approved anabolic treatment for osteoporosis, is important in calcium-phosphate homeostasis. However, little is known about its potential therapeutic effects on other diseases. Here, we report that intermittent administration of PTH ameliorated non-alcoholic liver steatosis in diet-induced obese (DIO) mice and db/db mice, as well as fasting-induced hepatic steatosis. <italic>In vitro</italic>, PTH inhibits palmitic acid-induced intracellular lipid accumulation in a parathyroid hormone 1 receptor (PTH1R)-dependent manner. Mechanistically, PTH upregulates the expression of genes involved in lipid β-oxidation and suppresses the expression of genes related to lipid uptake and <italic>de novo</italic> lipogenesis by activating the cAMP/PKA/CREB pathway. Taken together, our current finding proposes a new therapeutic role of PTH on NAFLD.</p>