Tomatidine, a Tomato Sapogenol, Ameliorates Hyperlipidemia and Atherosclerosis in ApoE-Deficient Mice by Inhibiting Acyl-CoA:cholesterol Acyl-transferase (ACAT)

• Published in: Journal of agricultural and food chemistry Vol. 60; no. 10; pp. 2472 - 2479
• Main Authors: Fujiwara, Yukio, Kiyota, Naoko, Tsurushima, Keiichiro, Yoshitomi, Makiko, Horlad, Hasita, Ikeda, Tsuyoshi, Nohara, Toshihiro, Takeya, Motohiro, Nagai, Ryoji
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14-03-2012
• Subjects: animal ovaries; Animals; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; atherogenesis; atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - enzymology; Atherosclerosis - genetics; Atherosclerosis - metabolism; Biological and medical sciences; Cell Line; Chinese hamsters; Cholesterol Esters - metabolism; Cricetinae; Disease Models, Animal; Down-Regulation; Female; Foam Cells - metabolism; Food industries; Fruit and vegetable industries; Fundamental and applied biological sciences. Psychology; glycoalkaloids; Humans; hyperlipidemia; Hyperlipidemias - drug therapy; Hyperlipidemias - enzymology; Hyperlipidemias - genetics; Hyperlipidemias - metabolism; low density lipoprotein cholesterol; Lycopersicon esculentum - chemistry; macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; oral administration; Plant Extracts - administration & dosage; Sterol O-Acyltransferase - antagonists & inhibitors; Sterol O-Acyltransferase - genetics; Sterol O-Acyltransferase - metabolism; Tomatine - administration & dosage; Tomatine - analogs & derivatives; tomatoes; atherosclerosis; tomatidine; macrophage; tomato; acyl-CoA:cholesterol acyl-transferase; Vegetables; Enzyme; Transferases; Rodentia; Lipids; Cardiovascular disease; Tomato; Cholesterol; Vascular disease; Vertebrata; Mammalia; Mouse; Atherosclerosis
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf204197r

It was previously revealed that esculeoside A, a new glycoalkaloid, and esculeogenin A, a new aglycon of esculeoside A, contained in ripe tomato ameliorate atherosclerosis in apoE-deficent mice. This study examined whether tomatidine, the aglycone of tomatine, which is a major tomato glycoalkaloid, also shows similar inhibitory effects on cholesterol ester (CE) accumulation in human monocyte-derived macrophages (HMDM) and atherogenesis in apoE-deficient mice. Tomatidine significantly inhibited the CE accumulation induced by acetylated LDL in HMDM in a dose-dependent manner. Tomatidine also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-CoA:cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that tomatidine suppresses both ACAT-1 and ACAT-2 activities. Furthermore, the oral administration of tomatidine to apoE-deficient mice significantly reduced levels of serum cholesterol, LDL-cholesterol, and areas of atherosclerotic lesions. The study provides the first evidence that tomatidine significantly suppresses the activity of ACAT and leads to reduction of atherogenesis.