Chemical Inhibition of Citrate Metabolism Alters Body Fat Content in Mice

Introduction

Obesity is one of the most relevant health problems in westernized countries, and affects more than 300 million people worldwide [1]. Multiple factors contribute to the obese phenotype, including altered energy intake and fuel dissipation. Recently, impaired mitochondrial metabolism has been suggested as playing a possible role in the obese phenotype; specifically, in silico analyses of published literature on obesity and energy metabolism revealed a putative role for mitochondrial aconitase, the enzyme that converts citrate into isocitrate, in aberrant storage of exogenous nutrients [2]. The authors suggest that reduced activity of mitochondrial aconitase would cause impaired oxidative phosphorylation of nutrient intermediates, and might also lead to increased de novo synthesis of fatty acids due to excess citrate accumulation subsequent to reduced mitochondrial conversion into isocitrate.

This study aimed to test this hypothesis using fluoroacetate, a competitive inhibitor of citrate metabolism. We chronically exposed C57bl6 mice to this particular substance, which led to significant alterations in citrate metabolism and body composition, specifically a reduction of body fat content.

References

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