Overexpression of Slc22a18 facilitates fat accumulation in mice

• Published in: Biochemical and biophysical research communications Vol. 712-713; p. 149922
• Main Authors: Yamamoto, Takashi, Iizuka, Yoko, Izumi-Yamamoto, Kozue, Shirota, Midori, Mori, Nobuko, Tahara, Yoshikazu, Fujita, Toshiro, Gotoda, Takanari
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.06.2024
• Subjects: Adipocyte; Adipocytes - metabolism; Adipose Tissue - metabolism; Adiposity - genetics; Animals; Cells, Cultured; Fatty liver; Fatty Liver - genetics; Fatty Liver - metabolism; Fatty Liver - pathology; Hepatocytes - metabolism; Lipid Metabolism - genetics; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Organic Cation Transport Proteins - genetics; Organic Cation Transport Proteins - metabolism; Rats; Rats, Sprague-Dawley; SHR; SLC22A18; Solute carrier; Triglycerides - metabolism; Adipocyte; Solute carrier; Fatty liver; SHR; SLC22A18
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.149922

We previously reported that solute carrier family 22 member 18 (Slc22a18) regulates lipid accumulation in 3T3-L1 adipocytes. Here, we provide additional evidence derived from experiments with adenoviral vector expression and genetic manipulation of mice. In primary cultured rat hepatocytes, adenoviral overexpression of mouse Slc22a18 increased triglyceride accumulation and triglyceride synthetic activity, which was decreased in an adenoviral knockdown experiment. Adenoviral overexpression of mouse Slc22a18 in vivo caused massive fatty liver in mice, even under normal dietary conditions. Conversely, adenoviral knockdown of mouse Slc22a18 reduced hepatic lipid accumulation induced by a high-glucose and high-sucrose diet. We created Slc22a18 knockout mice, which grew normally and showed no obvious spontaneous phenotypes. However, compared with control littermates, the knockout mice exhibited decreased hepatic triglyceride content under refeeding conditions, significantly reduced epididymal fat mass, and tended to have lower liver weight in conjunction with leptin deficiency. Finally, we created transgenic mice overexpressing rat Slc22a18 in an adipose-specific manner, which had increased body weight and epididymal fat mass primarily because of increased adipocyte cell volume. In these transgenic mice, a positive correlation was observed between adiposity and the expression levels of the rat Slc22a18 transgene. Taken together, these results indicate that Slc22a18 has positive effects on lipid accumulation in vivo. •Adenoviral overexpression of Slc22a18 causes massive fatty liver•Adenoviral knockdown of Slc22a18 ameliorates fatty liver•Protection of Slc22a18 knockout mice from lipid accumulation•Increased adiposity of adipose-specific Slc22a18 transgenic mice•A positive correlation observed between fat mass and transgene expression