FASEB J. 2025 Jun 15;39(11):e70703. doi: 10.1096/fj.202500738R.
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.
PMID:40489164 | DOI:10.1096/fj.202500738R
