Aspartate Is A Determinant of TNF-α Biogenesis in Sub-Saharan Africa: Insight Into the Pathogenesis of Noncommunicable Diseases

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.