Lipidomics: New Frontier of the Ketogenic Diet

Abstract

Lipidomics is the discipline that studies lipid changes that occur during cellular metabolism. This new approach can be applied to the ketogenic diet (KD) where fats are the predominant macronutrient. After a few days of reduced carbohydrate consumption, glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle and for the supply of glucose to the central nervous system. The alternative energy source is derived from the overproduction of acetyl coenzyme A. This condition, called ketogenesis, leads to the production of higher-than-normal levels of so-called ketone bodies. The acceleration of the production of monounsaturated fats (MF) is so characteristic of obesity that the palmitic-palmitoleic track is indicated as a biomarker even the risk of weight gain. Palmitoleic is known as lipoquine, as it regulates the fat transfer from adipose tissue to muscle. In obesity it increases because it is a defence mechanism of the body to transport fats to the muscle, thus avoiding their excessive accumulation in the liver. The saturated/MF ratio indicates the level of stiffness of the membrane. The increase in membrane stiffness leads to a decrease in the number of insulin receptors predisposing to the onset of diabetes. Each cellular compartment has its own lipid content which can be monitored by lipidomics but the erythrocyte membrane has been shown to have the suitable characteristics to become an important site for lipidomic analysis. Conclusions: KD could be customized based on the results of the membrane lipidomic analysis. The lipidomic profile of an obese subject is characterized by an imbalance of PUFA in favor of omega-6 and by an excess of MF. This imbalance must be taken into consideration in the formulation of the KD protocol: only in this way, the epigenetic structure will be favorable to the establishment of a new balance unfavorable to fat accumulation.