Ep. 10: Dalton Graham: How to Induce Fatty Liver—with Dr. Brian Kerley

Dr. Kerley and I are joined by Dalton Graham, a student who found himself in a liver pathology lab at Tulane. He had the interesting idea to test if a high-linoleic acid diet could be shown to produce fatty liver disease at the same time it was causing obesity.
The scientists in the lab required a little convincing that this was a worthy experiment, but one day he arrived to find all the materials he need waiting for him.
Be careful what you wish for! Find out how it turned out.
Graham, D. S., Liu, G., Arasteh, A., Yin, X.-M., & Yan, S. (2023). Ability of High Fat Diet to Induce Liver Pathology Correlates with the Level of Linoleic Acid and Vitamin E in the Diet. PLOS ONE, 18(6), e0286726. https://doi.org/10.1371/journal.pone.0286726

Biography:
• Dalton is currently a PhD student at University of Florida, studying Biochemistry with a focus on metabolism. When he wrote the paper we are discussing, he was an undergrad, and then grad student at Tulane University, studying Biochemical Engineering and Pathology.
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Co-host Dr. Brian Kerley
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Tucker Goodrich
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Show Notes
“Alvheim papers out of the NIH”
Alvheim, A. R., Malde, M. K., Osei‐Hyiaman, D., Hong, Y. H., Pawlosky, R. J., Madsen, L., Kristiansen, K., Frøyland, L., & Hibbeln, J. R. (2012). Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity. Obesity, 20(10), 1984–1994. https://doi.org/10.1038/oby.2012.38
Alvheim, A. R. (2012). Dietary linoleic acid induces obesity through excessive endocannabinoid activity [Doctor of Philosophy, The University of Bergen]. https://bora.uib.no/bora-xmlui/handle/1956/5962
NAFLD discovered in 1980:
Ludwig, J., Viggiano, T. R., McGill, D. B., & Oh, B. J. (1980). Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clinic Proceedings, 55(7), 434–438.
Liver transplants and NAFLD:
Lindenmeyer, C. C., & McCullough, A. J. (2018). The Natural History of Nonalcoholic Fatty Liver Disease—An Evolving View. Clinics in Liver Disease, 22(1), 11. https://doi.org/10.1016/j.cld.2017.08.003
Linoleic acid and breast milk:
Goodrich, T. D. (2022, September 1). Podcast Ep. 5: Prof. Tom Brenna on Omega-3 and Omega-6 in Human Health—with Dr Brian Kerley [Blog]. Yelling Stop. http://yelling-stop.blogspot.com/2022/09/podcast-ep-5-prof-tom-brenna-on-omega-3.html
Gornoski, D. (2021, June 15). Bruce German on How Human Milk Does the Body Good (Jun 15 2021) [Mp3]. https://podcastaddict.com/episode/124448388
Speakman paper on lethargy:
Speakman, J. R., De Jong, J. M. A., Sinha, S., Westerterp, K. R., Yamada, Y., Sagayama, H., Ainslie, P. N., Anderson, L. J., Arab, L., Bedu-Addo, K., Blanc, S., Bonomi, A. G., Bovet, P., Brage, S., Buchowski, M. S., Butte, N. F., Camps, S. G. J. A., Cooper, J. A., Cooper, R., … Wong, W. W. (2023). Total Daily Energy Expenditure Has Declined Over the Past Three Decades Due to Declining Basal Expenditure, Not Reduced Activity Expenditure. Nature Metabolism, 5(4), 579–588. https://doi.org/10.1038/s42255-023-00782-2
Vitamin E:
Masterjohn, C. (2017, June 24). 032: Is Coconut Oil Killing Us? [Substack newsletter]. Harnessing the Power of Nutrients. https://chrismasterjohnphd.substack.com/p/041-is-coconut-oil-killing-us
Raghavamenon, A., Garelnabi, M., Babu, S., Aldrich, A., Litvinov, D., & Parthasarathy, S. (2009). α-Tocopherol Is Ineffective in Preventing the Decomposition of Preformed Lipid Peroxides and May Promote the Accumulation of Toxic Aldehydes: A Potential Explanation for the Failure of Antioxidants to Affect Human Atherosclerosis. Antioxidants & Redox Signaling, 11(6), 1237–1248. https://doi.org/10.1089/ars.2008.2248
NAFLD and Fructose:
Vos, M. B., Weber, M. B., Welsh, J., Khatoon, F., Jones, D. P., Whitington, P. F., & McClain, C. J. (2009). Fructose and Oxidized LDL in Pediatric Nonalcoholic Fatty Liver Disease: A Pilot Study. Archives of Pediatrics & Adolescent Medicine, 163(7), 674–675. https://doi.org/10.1001/archpediatrics.2009.93
Cardiolipin:
Goodrich, T. (2016, February 5). The Cause of Metabolic Syndrome: Excess Omega-6 Fats (Linoleic Acid) in Your Mitochondria. Yelling Stop. http://yelling-stop.blogspot.com/2016/02/the-cause-of-metabolic-syndrome-excess.html

Quotable:
“I made a presentation about the role of excess linoleic acid in liver diseases. …I sat down and I pitched it… to the individuals in that lab. At first they didn’t really get it… I remember when I first finished laying out the mechanisms and why this is needed. Typically at the end of a presentation there are a bunch of questions, and there was just… silence.
“They’d never been presented with this idea that lipid peroxidation (or oxidative stress) manifests itself mainly due to this dietary factor—that no one seems to realize because it’s so ubiquitous.”
“These animals that are eating the higher linoleic acid they appear physical slower.”
“The females that were fed the high linoleic acid, they actually lost a lot of their fur [while under stress]. We couldn’t continue the experiment with them.”
“I don’t think they understood the importance of [linoleic acid] in the real world.”