Associate Professor of Internal Medicine and
Adjunct Associate Professor of Biochemistry and of Nutrition and Integrative Physiology
B.S. Hofstra University
M.D. Albert Einstein College of Medicine
Ph.D. Albert Einstein College of Medicine
Amnon Schlegel's Lab Page
Amnon Schlegel's PubMed Literature Search
Molecular Biology Program
Biological Chemistry Program
Metabolism, type 2 diabetes mellitus, atherosclerosis, fat, cholesterol, glucose
My lab identifies and studies novel factors that participate in glucose and lipid metabolism. While much of the work has been in done in zebrafish (Benítez-Santana and Schlegel, 2017; Cruz-Garcia and Schlegel, 2014; Hugo et al., 2012; Karanth, et al., 2013; Hugo and Schlegel, 2017a; Hugo and Schlegel, 2017b), the lab takes a molecular, cellular, and physiological approach approach (from test tubes to mice to patient samples). Ultimately, we hope to find critical “control nodes” of metabolic flux and regulation that would prompt development of novel therapies to treat disorders marked by deranged lipid metabolism: type 2 diabetes mellitus, non-alcoholic fatty liver disease, obesity, and atherosclerotic cardiovascular disease (Schlegel and Gut, 2015).
There are three main area of work in the lab.
1. Regulation of Liver Glucose Metabolism
The complex genetics of type 2 diabetes is the central of focus in the laboratory. We recently established that the transcription factor FOXN3, whose encoding gene locus is associated with fasting blood glucose is a previously unrecognized regulator of hepatic glucose production and cross-talk with the alpha cells of the endocrine pancreas (Karanth et al. 2016; Karanth et al. 2018). Mechanistic studies on this project focus on mouse physiology and gene regulation.
2. Lipid Droplet Cell Biology
Zebrafish is an excellent model organism to study lipid physiology (Schlegel, 2016). We identified a critical role for the nuclear hormone receptor Liver X Receptor (LXR) in diverting absorbed dietary fats to a temporary storage pool in enterocyte cytoplasmic lipid droplets (Cruz-Garcia and Schlegel, 2014: Benitez-Santana, 2017). The consequences of this diversion of absorbed lipids are favorable: protection from high fat-diet induced dyslipidemia and hepatic steatosis. We are focusing on carefully studying the function of a direct transcriptional target of LXR encoding Acyl-CoA synthetase, long-chain member 3 (Acsl3), an enzyme required for physically diverting fatty acids to cytoplasmic lipid droplets, and away from chylomicrons. This project uses cutting edge live-imaging techniques in zebrafish larvae, as well as cell-based approaches.
3. Forward Genetic Screens
We completed a forward genetic screen for novel mutants affecting liver lipid accumulation. Projects are available to positionally clone and characterize the lesions, going as deeply into mechanisms as possible (Hugo et al., 2012; Karanth et al., 2013; Hugo and Schlegel, 2017a; Hugo and Schlegel, 2017b).
- Benítez-Santana T, and Schlegel (2017). Role of intestinal LXRα in regulating post-prandial Lipid excursion and diet-induced hypercholesterolemia and hepatic lipid accumulation. Front Physiol 8, 280.
- Cruz-Garcia L, and Schlegel A (2014). Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids. J Lipid Res 55, 1944-1958.
- Hugo SE, Cruz-Garcia L, Karanth S, Anderson RM, Stainier DYR and Schlegel A (2012). A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting. Genes Dev 26, 282-293.
- Hugo SE, and Schlegel A (2017a). A genetic model to study increased hexosamine biosynthetic flux. Endocrinology 158, 2420–242.
- Hugo SE, and Schlegel A (2017b). A genetic screen for zebrafish mutants with hepatic steatosis identifies a locus required for larval growth. J Anat 230,407-413.
- Karanth S, Tran VM, Balagurunathan K, and Schlegel A (2013). Polyunsaturated fatty acyl- Coenzyme As are inhibitors of cholesterol biosynthesis. Dis Model Mech 6, 1365-1377.
- Karanth S, Zinkhan EK, Hill JT, Yost HJ, and Schlegel A (2016). FOXN3 regulates hepatic glucose utilization. Cell Rep 15, 2745-2755.
- Karanth S, Adams JD, Serrano MDL, Quittner-Strom EB, Simcox J, Villanueva CJ, Ozcan L, Holland WL, Yost HJ, Vella A, and Schlegel A. A A Hepatocyte FOXN3- α Cell Glucagon Axis Regulates Fasting Glucose. Cell Rep 24, 312-319.
- Schlegel A (2016) Zebrafish Models for Dyslipidemia and Atherosclerosis Research. Front Endocrinol (Lausanne) 7, 159.
- Schlegel A and Gut P (2015) Metabolic insights from zebrafish genetics, physiology, and chemical biology. Cell Mol Life Sci. 72, 2249-60.