AUTHOR=Huang Wen-wen , Hong Bi-hong , Bai Kai-kai , Tan Ran , Yang Ting , Sun Ji-peng , Yi Rui-zao , Wu Hao 

TITLE=Cis- and Trans-Palmitoleic Acid Isomers Regulate Cholesterol Metabolism in Different Ways

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.602115

DOI=10.3389/fphar.2020.602115

ISSN=1663-9812

ABSTRACT=<p>Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms whereby <italic>cis</italic>-palmitoleic acid (<italic>c</italic>POA) and <italic>trans</italic>-palmitoleic acid (<italic>t</italic>POA) promote cholesterol homeostasis and ameliorate hypercholesterolemia remain elusive. To investigate the effects of <italic>c</italic>POA and <italic>t</italic>POA on cholesterol metabolism and its mechanisms, we induced hypercholesterolemia in mice using a high-fat diet and then intragastrically administered <italic>c</italic>POA or <italic>t</italic>POA once daily for 4 weeks. <italic>t</italic>POA administration reduced serum cholesterol, low-density lipoprotein, high-density lipoprotein, and hepatic free cholesterol and total bile acids (TBAs). Conversely, <italic>c</italic>POA had no effect on these parameters except for TBAs. Histological examination of the liver, however, revealed that <italic>c</italic>POA ameliorated hepatic steatosis more effectively than <italic>t</italic>POA. <italic>t</italic>POA significantly reduced the expression of 3-hydroxy-3-methyl glutaryl coenzyme reductase (HMGCR), LXRα, and intestinal Niemann-Pick C1-Like 1 (NPC1L1) and increased cholesterol 7-alpha hydroxylase (CYP7A1) in the liver, whereas <italic>c</italic>POA reduced the expression of HMGCR and CYP7A1 in the liver and had no effect on intestinal NPC1L1. In summary, our results suggest that <italic>c</italic>POA and <italic>t</italic>POA reduce cholesterol synthesis by decreasing HMGCR levels. Furthermore, <italic>t</italic>POA, but not <italic>c</italic>POA, inhibited intestinal cholesterol absorption by downregulating NPC1L1. Both high-dose <italic>t</italic>POA and <italic>c</italic>POA may promote the conversion of cholesterol into bile acids by upregulating CYP7A1. <italic>t</italic>POA and <italic>c</italic>POA prevent hypercholesterolemia via distinct mechanisms.</p>