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.