Glycerol and lipid metabolism. Additionally, the secondary metabolite

Glycerol
(1,2,3-propanetriol) is a polyalcohol that can be produced from glucose,
protein and glycerolipid metabolic pathways (endogenous glycerol) or taken up
from dietary fats (exogenous glycerol). Glycerol is the carbon backbone for the
de novo synthesis of TAG and phospholipids and
it 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, a
by-product from glycolysis acting as a shuttle of electrons from the cytosol
into the mitochondria 75,76.

In
the liver, G3P is used in glycolysis and gluconeogenesis, and, in muscle it is
an energy substrate via the G3P shuttle, which has a key role in oxidizing
glucose rapidly and generating adenosine triphosphate (ATP) in the mitochondria
through the oxidation of G3P 77. In the
feeding state, glycerol contribution to gluconeogenesis is reduced but it
increases considerably in fasting, becoming an important source for
gluconeogenesis along with lactate, pyruvate, alanine and glutamine 37. In prolonged
fasting, glycerol can be used as the only source for gluconeogenesis, since
glycogen reserves are depleted within two fasting days 75.

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Besides the exogenous glycerol, the amount of plasma glycerol is also
dependent on the amount reabsorbed in kidney microtubules; however, its main
source is the adipose tissue. In situations of negative energy balance, such as
fasting or exercise, lipolysis of TAG stored in white adipose tissue yields
glycerol and FFA that are released in the bloodstream to be used by other
organs as energy source 78,79.

The above-mentioned metabolic
reactions occur exclusively in intracellular compartments forcing glycerol
molecules to move across different tissues. It is now well established that glycerol
permeation through membranes is facilitated by aquaglyceroporins and thus
regulation of glycerol transport by AQPs is crucial to control specific
metabolic mechanisms such as lipogenesis, lipolysis, gluconeogenesis and energy
homeostasis 80,76,81. Table 1 lists the
aquaglyceroporins expressed in organs and tissues involved in energy
homeostasis and their implication in glycerol balance.