Journal Article Ppublish
PubMed: 40489164 DOI: 10.1096/fj.202500738R
Aspartate Is A Determinant of TNF-α Biogenesis in Sub-Saharan Africa: Insight Into the Pathogenesis of Noncommunicable Diseases.
FASEB J 39(11):e70703
Authors: Stephen W Bickler, David M Cauvi, Jack A Gilbert, Romeo C Ignacio, Emmanuel A Ameh, Robert T Schooley, Emilia V Noormahomed
Affiliations
- Department of Surgery, Division of Pediatric Surgery, UC San Diego, San Diego, California, USA.
- Division of Pediatric Surgery, Rady Children's Hospital, San Diego, USA.
- University of California, San Diego, Scripps Institution of Oceanography, La Jolla, California, USA.
- Department of Pediatrics, UC San Diego, San Diego, California, USA.
- Division of Pediatric Surgery, Department of Surgery, National Hospital, Abuja, Nigeria.
- Department of Medicine, UC San Diego, San Diego, California, USA.
- Department of Microbiology, Faculty of Medicine, Universidade Eduardo Mondlane (UEM), Maputo, Mozambique.
Abstract
Urbanization in sub-Saharan Africa is characterized by a shift toward a proinflammatory state and rising rates of noncommunicable diseases. The biological mechanism(s) linking changes in environmental factors to health and disease are incompletely understood. We propose a TNF-hypersecreting phenotype described in rheumatoid arthritis patients also has a role in the inflammatory response differences observed between rural and urban populations living in Africa. The mechanism involves insufficient mitochondrial aspartate production, failed NAD + regeneration, ER membrane expansion, and enhanced biogenesis of TNF-α. Supporting data show serum and stool aspartate levels decline with urbanization, and TNF-α production inversely correlates with stool aspartate levels across a spectrum of socioeconomic development. These findings suggest a new hypothesis for the inflammatory differences between rural and urban populations and their role in noncommunicable diseases like atherosclerosis.
MeSH
Noncommunicable Diseases, Organelle Biogenesis