Bottom Line: After developing a noninvasive nanosensor to detect the progression of fatty liver disease in mice, researchers at the Sloan Kettering Institute have determined that there is a long-term effect on liver macrophages from eating a high-fat and high-sugar diet, even after switching back to a normal diet. These findings suggest that a poor diet can cause long-term effects on the liver that continue long after the resumption of a normal diet.
Findings and Method: Daniel Heller, PhD, and colleagues developed the nanosensor to measure fat specifically in the lysosomes of mice. Lysosomes serve as the waste disposal system of cells. The nanosensor is made of carbon nanotubes and lights up in near-infrared wavelengths in the liver. It changes color in the presence of fat, giving a measurement that can be easily detected through the tissues of the body in a noninvasive manner.
After giving the sensor to a fatty liver disease mouse model, researchers found that the nanosensor detected changes in the liver at the early stages of liver disease. The sensor found that mice given a high-fat, high-sugar diet, for even a short time accumulated fat in the lysosomes of the Kupffer cells. These cells normally clear materials, such as dead cells, from the bloodstream. Normally, no obvious changes are found in the liver of these mice at this early stage of the disease, which progresses to nonalcoholic steatohepatitis, the advanced form of which can progress to liver cancer.
Researchers found that after the mice were switched back to a normal diet, the accumulated fat remained, even long after the unhealthy diet had ended. This finding suggests that diet has previously unknown long-term effects on liver health.
Author Comment: “This work illustrates the lasting effects of a poor diet and the ongoing risks associated with diets high in fat and sugar,” explained Dr. Heller. “We are encouraged by the success we had in testing this new sensor and will continue to explore how we can use this technology to potentially diagnose fatty liver disease noninvasively and to find new treatments.”
Journal: “An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo” was published in Science Translational Medicine on October 3, 2018. Dr. Heller served as corresponding author.
Funding: This work was supported, in part, by a National Institutes of Health New Innovator Award (DP2-HD075698), Cancer Center Support Grant (P30 CA008748), and grant, NIHNS081981 (DSO); a National Science Foundation Faculty Early Career Development Program Award (1752506); the Ara Parseghian Medical Research Fund through the Michael, Marcia, and Christa Parseghian Endowment for Excellence in Niemann-Pick Type C Research; the Honorable Tina Brozman Foundation for Ovarian Cancer Research; the Expect Miracles Foundation; the Anna Fuller Fund; Cycle for Survival; William H. Goodwin, Alice Goodwin, and the Commonwealth Foundation for Cancer Research; the Pershing Square Sohn Cancer Research Alliance; and MSK’s Louis V. Gerstner, Jr. Young Investigators Fund, Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center; Center for Experimental Therapeutics; Imaging and Radiation Sciences Program; Frank A. Howard Fellows Program, Department of Radiation Oncology, research and development funds, and the Center for Molecular Imaging and Nanotechnology.