What the study found
A Western diet and palmitic acid, a saturated fat, were associated with iron-dependent ferroptotic injury in the enteric nervous system, which is the network of nerves that controls the gut. The findings also linked these exposures to delayed colonic transit and damage to vulnerable enteric neurons.
Why the authors say this matters
The authors suggest these findings are relevant to diet-associated enteric neuropathy, meaning nerve injury in the gut linked to diet. They conclude the human myenteric ganglia results support translational relevance.
What the researchers tested
The researchers used mouse models, cell systems, and human myenteric ganglia. Mice were fed a control diet or a Western diet for 12 weeks, with or without AAV9-MaCPNS2 delivery of Nfe2l2 to enteric neurons, and colonic motility was measured with a bead-expulsion assay.
What worked and what didn't
In Western diet-fed mice, colonic transit was delayed, TfR1 and FTH-1 were increased, and nNOS neurons were more vulnerable; these changes were reversed by Nfe2l2 overexpression. In palmitic acid-treated neuronal cells, RNA-seq showed disrupted neurotransmitter signaling, reduced mitochondrial and antioxidant programs, and increased iron import and lipid peroxidation signatures. Palmitic acid also increased labile iron, mitochondrial ROS, membrane depolarization, Ca2+ dysregulation, 4-HNE, and Mfrn2, while ferrostatin-1 preserved mitochondrial integrity, viability, and ENS function. In human nhMPG, palmitic acid induced enteric neuronal iron loading and ferroptosis.
What to keep in mind
The abstract does not describe detailed limitations beyond the models used. The findings are based on murine models, in vitro systems, and human myenteric ganglia, so the summary available here does not state how broadly the results apply beyond those settings.
Key points
- Western diet was associated with delayed colonic transit in mice.
- Palmitic acid increased markers linked to iron dysregulation and lipid peroxidation.
- Nfe2l2 overexpression reversed Western diet-associated changes in mice.
- Ferrostatin-1 preserved mitochondrial integrity, cell viability, and ENS function in experimental systems.
- Human myenteric ganglia showed palmitic acid-induced neuronal iron loading and ferroptosis.
Disclosure
- Research title:
- Western diet and palmitic acid linked to enteric neuron injury
- Authors:
- Arun Balasubramaniam, Dmitrii Pavlov, Yunpeng Du, Jeremy Reeves, Alan Harzman, Yunshan Liu, Francesca Cingolani, Xinxu Yuan, Jay M. Patel, Simon M. Mwangi, Peijian He, C. Michael Hart, Wenhui Hu, Fievos L. Christofi, Shanthi Srinivasan
- Institutions:
- Emory University, The Ohio State University, Virginia Commonwealth University, Atlanta VA Health Care System
- Publication date:
- 2026-04-21
- OpenAlex record:
- View
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