Selected Grantee Publications
Fructose Stimulated De Novo Lipogenesis Is Promoted by Inflammation
Jelena et al., Nature Metabolism. 2020.
https://pubmed.ncbi.nlm.nih.gov/32839596
Non-alcoholic fatty liver disease (NAFD) affects 30% of adult Americans. While NAFD starts as simple steatosis with little liver damage, its severe manifestation as non-alcoholic steatohepatitis (NASH) is a leading cause of liver failure, cirrhosis, and cancer. Fructose consumption is proposed to increase the risk of hepatosteatosis and NASH. Excessive intake of fructose causes barrier deterioration and low-grade endotoxemia. Using a mouse model, the study examined the mechanism of how fructose triggers these alterations and their roles in hepatosteatosis and NASH pathogenesis. The results demonstrated that microbiota-derived Toll-like receptor (TLR) agonists promote hepatosteatosis without affecting fructose-1-phosphate (F1P) and cytosolic acetyl-CoA. Activation of mucosal-regenerative gp130 signaling, administration of the YAP-induced matricellular protein CCN1 or expression of the antimicrobial peptide Reg3b (beta) counteract fructose-induced barrier deterioration, which depends on endoplasmic-reticulum stress and subsequent endotoxemia. Endotoxin engages TLR4 to trigger TNF production by liver macrophages, thereby inducing lipogenic enzymes that convert F1P and acetyl-CoA to fatty acid in both mouse and human hepatocytes. The finding may be of relevance to several common liver diseases and metabolic disorders. Supported by ORIP (S10OD020025), NCI, NIEHS, NIDDK, NIAID, and NIAAA.
Fluorescence-Based Sorting of Caenorhabditis elegans via Acoustofluidics
Zhang et al., Lab on a Chip. 2020.
The authors present an integrated acoustofluidic chip capable of identifying worms of interest based on expression of a fluorescent protein in a continuous flow and then separate them in a high-throughput manner. Utilizing planar fiber optics, their acoustofluidic device requires no temporary immobilization of worms for interrogation/detection, thereby improving the throughput. The device can sort worms of different developmental stages (L3 and L4 stage worms) at high throughput and accuracy. In their acoustofluidic chip, the time to complete the detection and sorting of one worm is only 50 ms, which outperforms nearly all existing microfluidics-based worm sorting devices. Supported by ORIP (R43OD024963), NIEHS, and NIDDK.