Cis- and Trans-Palmitoleic Acid Isomers Regulate Cholesterol Metabolism in Different Ways
Wenwen Huang, Bihong Hong, Kaikai Bai, Ran Tan, Ting Yang, Jipeng Sun, Ruizao Yi, Hao Wu
Abstract
Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms whereby cis -palmitoleic acid ( c POA) and trans -palmitoleic acid ( t POA) promote cholesterol homeostasis and ameliorate hypercholesterolemia remain elusive. To investigate the effects of c POA and t POA on cholesterol metabolism and its mechanisms, we induced hypercholesterolemia in mice using a high-fat diet and then intragastrically administered c POA or t POA once daily for 4 weeks. t POA administration reduced serum cholesterol, low-density lipoprotein, high-density lipoprotein, and hepatic free cholesterol and total bile acids (TBAs). Conversely, c POA had no effect on these parameters except for TBAs. Histological examination of the liver, however, revealed that c POA ameliorated hepatic steatosis more effectively than t POA. t 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 c POA reduced the expression of HMGCR and CYP7A1 in the liver and had no effect on intestinal NPC1L1. In summary, our results suggest that c POA and t POA reduce cholesterol synthesis by decreasing HMGCR levels. Furthermore, t POA, but not c POA, inhibited intestinal cholesterol absorption by downregulating NPC1L1. Both high-dose t POA and c POA may promote the conversion of cholesterol into bile acids by upregulating CYP7A1. t POA and c POA prevent hypercholesterolemia via distinct mechanisms.