Oren Rom: Connecting Amino Acid and Lipid Metabolism in MASH
Oren Rom, Assistant Vice Chancellor for Research at LSU Health Shreveport, shared a post on LinkedIn about a recent article he and his colleagues co-authored, published in JCL, adding:
“When amino acids and lipids talk, the liver listens!
Thrilled to share our latest publication in The Journal of Clinical Investigation family of journals, uncovering a previously unrecognized connection between aminoacid and lipid metabolism that regulates MASH and liver fibrosis!
Our study began with a discovery in livers from patients and animal models with metabolic liver disease, MASLD, MASH. We found that the naturally occurring lipidated amino acid, N-oleoyl-leucine (C18:1-Leu), was markedly reduced in diseased livers, and that lower levels were associated with more severe MASH and fibrosis.
C18:1-Leu sits at the intersection of two major metabolic pathways.
It is generated by linking the amino acid leucine to the fatty acid oleate, revealing an unexpected metabolic connection between amino acid and lipid metabolism in the liver.
We found that this pathway becomes impaired in MASH, and that restoring it by increasing PM20D1, the enzyme that produces C18:1-Leu, or by administering C18:1-Leu:
- Enhances PPARα-dependent fatty acid oxidation and helps the liver burn excess fat
- Suppresses CCL2-dependent inflammatory monocyte recruitment
- Reduces liver inflammation and fibrosis
- Improves both developing and established MASH in preclinical models
This naturally occurring metabolic pathway appears to target two major drivers of MASH simultaneously: abnormal lipid metabolism and inflammation.
While much more work is needed before translation to patients, our findings identify a new metabolic pathway with exciting therapeutic potential for MASH and liver fibrosis.
What makes this work especially meaningful to me is the team behind it!
Very proud of our co-first authors, Sumit Kumar Anand, Sandeep Das, and Fabio Arias Bordajandi!
This study reflects a truly collaborative, multi-institutional Team Science involving: LSU Health Shreveport (Koral Richard, Sumati Rohilla, Alia Ghrayeb, Peyton McKinney, Dhananjay KUMAR,Ph.D, Nilesh Pandey, Jennifer Lee, Suman Mohajan, Gurranna Male, Alexandra Finney, Brenna Pearson-Gallion, Reethika Gade, Jemiah Maxie, Harpreet Kaur, Rajan Pandit, Cyrine Ben, Joseph Eniafe, Xiaolu Zhang, Andrew Yurochko, Wayne Orr, Nirav Dhanesha, Arif Yurdagul), University of Michigan (Lu Wang, Ying Zhao, Minerva Garcia-Barrio, Bo Wen, Duxin Sun, Jifeng Zhang, and Y. Eugene Chen), Ochsner Health (Kelley Nunez, Paul Thevenot, Ari Cohen), Wayne State University (Zhipeng Liu, Wanqing Liu), UT MD Anderson (Lin Tan, Jibin Ding, Eyal Gottlieb), UCLA (Yu Liu, Xin Huang, Bishuang Cai), University of Pittsburgh (Babak Razani, Fei Chang, Francisco Schopfer).
Deeply grateful to all of our co-authors, collaborators, trainees, and core facilities whose expertise, commitment, and collaborative spirit made this work possible. This is truly Team Science at its best!”
Title: Targeting lipidated amino acid deficiency mitigates fibrosis via a PPARα/CCL2 axis in metabolic dysfunction-associated steatohepatitis models
Authors: Sumit Kumar Anand, Sandeep Das, Fabio Arias, Koral S.E. Richard, Sumati Rohilla, Alia Ghrayeb, M. Peyton McKinney, Lu Wang, Lin Tan, Jibin Ding, Dhananjay Kumar, Nilesh Pandey, Jennifer Lee, Ying Zhao, Suman Mohajan, Gurranna Male, Kelley Nunez, Alexandra C. Finney, Brenna H. Pearson-Gallion, Reethika Gade, Jemiah Maxie, Yu Liu, Harpreet Kaur, Rajan Pandit, Cyrine Ben Dhaou, Joseph Eniafe, Xiaolu Zhang, Zhipeng Liu, Andrew D. Yurochko, Minerva T. Garcia-Barrio, Babak Razani, Fei Chang, Francisco J. Schopfer, Xin Huang, Bishuang Cai, Eyal Gottlieb, Bo Wen, Duxin Sun, Wanqing Liu, Paul T. Thevenot, Ari J. Cohen, Jifeng Zhang, Y. Eugene Chen, A. Wayne Orr, Nirav Dhanesha, Arif Yurdagul Jr., Oren Rom
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