agonists for this reaction are the
catecholamines, such as epinephrine and
norepinephrine. In poultry, glucagon is the
major lipolytic hormone. Binding of these
hormones to cell surface receptors causes
activation of adenyl cyclase, depending on
the balance between activation of the
stimulatory guanine nucleotide-binding
protein (Gsprotein) and activation of the
inhibitory Giprotein (Lafontan and Langin,
1995). Receptor types vary among tissues
and species in the relative activation of
these two G proteins. Agonists that activate
-adrenergic receptors cause activation of
Gs. Activation of Gsactivates adenyl cyclase,
which increases the concentration of cAMP
in the cell. In turn, cAMP activates protein
kinase A, which phosphorylates the regula-
tory subunit of hormone-sensitive lipase.
The activated hormone-sensitive lipase
then catalyses lipolysis of triacylglycerol.
Inhibition of lipolysis depends on a
greater activation of Gi proteins, which
inhibit adenyl cyclase and increase the
activity of phosphodiesterase, the enzyme
that degrades cAMP. Agonists that bind to
-adrenergic receptors activate Giand thus
suppress lipolysis (Lafontan and Langin,
1995). Factors such as insulin, adenosine
and the E series of prostaglandins are
associated with decreased activity of
hormone-sensitive lipolysis. Treatment of
animals with somatotropin results in an
indirect stimulation of lipolysis by increas-
ing the sensitivity of adipose tissue to the
effects of the catecholamines. Somatotropin
causes this increased sensitivity by
diminishing the ability of the Giproteins to
inhibit adenyl cyclase. Thus, suppression
of the inhibitory controls of lipolysis
allows higher rates of lipolysis to occur
during treatment with somatotropin.
Another factor controlling the relative
degree of lipolysis is the degree to which
fatty acids are re-esterified to form triacyl-
glycerols before they can diffuse out of the
cells. Insulin stimulates uptake of glucose
and glycolysis, increasing the supply of
glycerol-3-phosphate available for esterifica-
tion. Insulin also stimulates the activity of
the esterification pathway. Control of lipo-
lysis is interwoven tightly with regulation
of lipogenesis, so that the overall function
of adipose tissue to accrete or release
energy stores is coordinated according to
the physiological needs of the animal.Metabolism of Lipids in the Liver
Oxidation and ketogenesisThe liver takes up free fatty acids from
blood in proportion to their concentration.
Within the hepatocytes (liver cells), long-
chain fatty acids of 14 carbons or more are
activated by acyl-CoA synthetases found in
the microsomes and outer mitochondrial
membrane. Acyl-CoA may either enter the
mitochondria for oxidation or be esterified
within the endoplasmic reticulum (micro-
somes). Under conditions of increased fatty
acid uptake, the liver often produces large
amounts of the ketone bodies, acetoacetate
and -hydroxybutyrate, in the process
known as ketogenesis. The two main
factors regulating the degree to which fatty
acids are oxidized by the liver are the
supply of fatty acids to the liver via lipo-
lysis and the partitioning within hepato-
cytes between mitochondrial oxidation and
microsomal esterification.
No acyl-CoA synthetase enzymes that
can activate fatty acids with 14 carbons or
more are present within the mitochondrial
matrix (McGarry et al., 1989). Therefore,
entry of these long-chain fatty acids into
the mitochondria is regulated effectively by
the activity of the enzyme carnitine
palmitoyltransferase I (CPT-I). This enzyme
is an integral membrane protein of the outer
mitochondrial membrane, and catalyses
the formation of fatty acyl-carnitine from
fatty acyl-CoA and free L-carnitine. The
acyl-carnitine molecules are then trans-
ported across the mitochondrial membrane
by a specific carrier protein, and are recon-
verted to acyl-CoA within the mitochondrial
matrix by the action of CPT-II, a peripheral
protein of the inner mitochondrial mem-
brane. Short- and medium-chain fatty acids
(12 carbons or less) pass through the mito-
chondrial membrane and are activated by
acyl-CoA synthetases found within theLipid Metabolism 109