Adipose saturation reduces lipotoxic systemic inflammation and explains the obesity paradox

Biswajit Khatua, Bara El-Kurdi, Krutika Patel, Christopher Rood, Pawan Noel, Michael Crowell, Jordan R. Yaron, Sergiy Kostenko, Andre Guerra, Douglas O. Faigel, Mark Lowe, Vijay P. Singh

Research output: Contribution to journalArticlepeer-review

Abstract

Obesity sometimes seems protective in disease. This obesity paradox is predominantly described in reports from the Western Hemisphere during acute illnesses. Since adipose triglyceride composition corresponds to long-term dietary patterns, we performed a meta-analysis modeling the effect of obesity on severity of acute pancreatitis, in the context of dietary patterns of the countries from which the studies originated. Increased severity was noted in leaner populations with a higher proportion of unsaturated fat intake. In mice, greater hydrolysis of unsaturated visceral triglyceride caused worse organ failure during pancreatitis, even when the mice were leaner than those having saturated triglyceride. Saturation interfered with triglyceride’s interaction and lipolysis by pancreatic triglyceride lipase, which mediates organ failure. Unsaturation increased fatty acid monomers in vivo and aqueous media, resulting in greater lipotoxic cellular responses and organ failure. Therefore, visceral triglyceride saturation reduces the ensuing lipotoxicity despite higher adiposity, thus explaining the obesity paradox.

Original languageEnglish (US)
Article numbereabd6449
JournalScience Advances
Volume7
Issue number5
DOIs
StatePublished - Jan 29 2021
Externally publishedYes

ASJC Scopus subject areas

  • General

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