Hypothalamic Digoxin and Regulation of Body Mass Index

The hypothalamus produces digoxin, an endogenous membrane Na⁺-K⁺ ATPase inhibitor and regulator of neurotransmission. Digoxin being a steroidal glycoside, is synthesised by the isoprenoid pathway. In view of the reports of elevated digoxin levels in metabolic syndrome X with high body mass index, the isoprenoid pathway mediated 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 between digoxin status, body mass index and hemispheric dominance. The isoprenoid pathway metabolites, tryptophan / tyrosine catabolic patterns and membrane composition were assessed. In individuals with high body mass index an upregulated isoprenoid pathway with increased HMG CoA reductase activity, serum digoxin and dolichol levels and low ubiquinone levels were observed. The RBC membrane Na⁺-K⁺ ATPase activity and serum magnesium levels were decreased. The tyrosine catabolites (dopamine, morphine, epinephrine and norepinephrine) were reduced and the tryptophan catabolites (serotonin, quinolinic acid, strychnine and nicotine) were increased. There was an increase in membrane cholesterol : phospholipid ratio and a reduction in membrane glycoconjugates in individuals with high body mass index. The reverse patterns were seen in individuals with low body mass index. The patterns in individuals with high body mass index and low body mass index correlated with right hemispheric dominance and left hemispheric dominance respectively. Hemispheric dominance and digoxin status regulates the differential metabolic pattern observed in individuals with high and low body mass index.