Hypothalamic digoxin, hemispheric chemical dominance, and endocrine/metabolic/cellular regulation

The hypothalamus produces an endogenous membrane Na(+)-K+ ATPase inhibitor and regulator of neurotransmission, digoxin. Digoxin, a steroidal glycoside, is synthesized by the isoprenoid pathway. In view of the reports of elevated digoxin levels in metabolic syndrome X with high body mass index, the isoprenoid-mediated pathway biochemical cascade was assessed in individuals with high and low body mass index. It was also assessed in individuals with differing hemispheric dominance to find out the relationship among digoxin status, body mass index, and hemispheric dominance. The isoprenoid pathway metabolites, tryptophan/tyrosine catabolic patterns, glycoconjugate, and free radical metabolism, as well as membrane composition, were assessed. In individuals with high body mass index, an upregulated isoprenoid pathway with increased digoxin levels, increased glycoconjugates, and dolichol levels, reduced lysosomal stability, low ubiquinone levels with increased free radical generation, and increased membrane cholesterol:phospholipid ratio were observed. The reverse patterns were seen in individuals with a low body mass index. The patterns in individuals with a high body mass index and low body mass index correlated with right hemispheric dominance and left hemispheric dominance, respectively. Hemispheric dominance and digoxin status regulated the differential metabolic pattern observed in individuals with high and low body mass index. Hypothalamic digoxin/cerebral dominance can regulate the metabolic/endocrine function, as well as the structure/function of cellular organalle.