Glycerol of electrons from the cytosol into

Glycerol(1,2,3-propanetriol) is a polyalcohol that can be produced from glucose,protein and glycerolipid metabolic pathways (endogenous glycerol) or taken upfrom dietary fats (exogenous glycerol). Glycerol is the carbon backbone for thede novo synthesis of TAG and phospholipids andit is also an important intermediate in both carbohydrate and lipid metabolism.Additionally, the secondary metabolite of glycolysis glycerol-3-phosphate (G3P)is a key molecule in the regeneration of NAD+ from NADH, aby-product from glycolysis acting as a shuttle of electrons from the cytosolinto the mitochondria 75,76.

Inthe liver, G3P is used in glycolysis and gluconeogenesis, and, in muscle it isan energy substrate via the G3P shuttle, which has a key role in oxidizingglucose rapidly and generating adenosine triphosphate (ATP) in the mitochondriathrough the oxidation of G3P 77. In thefeeding state, glycerol contribution to gluconeogenesis is reduced but itincreases considerably in fasting, becoming an important source forgluconeogenesis along with lactate, pyruvate, alanine and glutamine 37. In prolongedfasting, glycerol can be used as the only source for gluconeogenesis, sinceglycogen reserves are depleted within two fasting days 75. Besides the exogenous glycerol, the amount of plasma glycerol is alsodependent on the amount reabsorbed in kidney microtubules; however, its mainsource is the adipose tissue. In situations of negative energy balance, such asfasting or exercise, lipolysis of TAG stored in white adipose tissue yieldsglycerol and FFA that are released in the bloodstream to be used by otherorgans as energy source 78,79.The above-mentioned metabolicreactions occur exclusively in intracellular compartments forcing glycerolmolecules to move across different tissues. It is now well established that glycerolpermeation through membranes is facilitated by aquaglyceroporins and thusregulation of glycerol transport by AQPs is crucial to control specificmetabolic mechanisms such as lipogenesis, lipolysis, gluconeogenesis and energyhomeostasis 80,76,81.

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Table 1 lists theaquaglyceroporins expressed in organs and tissues involved in energyhomeostasis and their implication in glycerol balance.

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