BMG Faculty Candidate Seminar
Department of Biochemistry and Molecular Genetics
“Unveiling organ crosstalk via circulating metabolite exchange at the whole-body level”
Hosung Bae, PhD
Postdoctoral Fellow
Department of Biological Chemistry
University of California Irvine
Abstract:
Mammalian organs continuously produce and consume circulating metabolites for organismal health and survival. However, the landscape of this fundamental process and its perturbation by diet and disease is unknown. To address this gap, I applied advanced analytical platforms, including liquid chromatography–mass spectrometry (LC-MS)-based metabolomics, lipidomics, and stable isotope tracing, to map the regulation of metabolites across organs in vivo.
In Part I of my research, I employed in vivo isotope tracing to investigate host–nutrient–microbiome interactions, revealing how fiber-adapted microbiota mitigate fructose-induced liver disease and how gut microbial metabolism modulates intestinal lipid absorption to protect against obesity and insulin resistance. I also applied this platform in large-animal models that closely resemble human physiology. For example, I demonstrated that cystic fibrosis (CF)-associated mutations intrinsically alter organ metabolism, reframing CF as a metabolic disorder from itsearliest stages.
In Part II, I generated a cross-organ metabolic atlas encompassing eleven key organs under fasting/feeding states, Western diet exposure, and LDL receptor (LDLR) deficiency-induced cardiovascular disease. This work revealed both feeding-dependent and -independent patterns of metabolite production and consumption, as well as mechanisms by which Western diet perturbs these fluxes through altered metabolite gradients and hormone signals. Notably, I found that both Western diet and LDLR deficiency promote the release of bile acids from extrahepatic organs, contributing to elevated circulating bile acid levels and vascular inflammation.
Together, these findings uncover complex inter-organ metabolic crosstalk and offer new
biochemical insights into the systemic effects of diet and the pathogenesis of metabolic diseases.
Hosts: Drs. Ali Shilatifard, Chairman, and Issam Ben-Sahra, Associate Professor, Department of Biochemistry and Molecular Genetics
Linda Jackson
Email