A modified technique for separation of serum free fatty
acids (FFA), t riglycerides, phospholipids and cholesterol
esters by adsorption chromatography on a system of two
columns, silicic acid and Florisil, has been elaborated for
preparing samples for gas-liquid chromatographic analysis of
serum lipid fatty acids.
An attempt was made to study the changes in fatty acid
composition of the various lipids in response to factors
influencing fatty acid mobilisation. The following stimuli
of fatty acid mobilisation were investigated: thyroid hormone,
human growth hormone (HGH),noradrenaline, prolonged fasting,
and acute and chronic ischaemic heart disease.
The effects of thyroid hormones were studied 1) after
administration of LT₃ to normal subjects; 2) after thyroid
hormone therapy to hypothyroid subjects and 3) after antithyroid
therapy to thyrotoxic subjects.
The effects of HGH were studied 1) during the daily
administration of HGH; 2) hourly after HGH injection; and
3) in patients with acromegaly.
The effects of noradrenaline were studied during its
The effects of fasting were studied when an overnight fast
was prolonged by 8 hours.
The effects of acute ischaemic heart disease were studied
on the day of myocardial infarction and on two subsequent
consecutive days. The effects of chronic ischaemic heart
disease were studied in patients with angina pectoris, and
those with a past history of myocardial infarction. One control
group consisted of middle aged males, and a second of postmenopausal females.
Percentage composition studies have revealed that increased
mobilisation of serum FFA due to any of the adipokinetic factors
studied was accompanied by statistically significant increases
in the percentage composition of serum FFA oleic acid. These
increases in oleic acid percentages were mostly accompanied
by parallel decreases in the percentage of FFA saturated acids:
stearic and palmitic acids. It is proposed that increases in
the percentage of FFA oleic acid were due to its higher
activity in transportation compared with saturated acids, in
the aqueous medium of adipose cells and plasma. This is
thought to be due to the physical properties of oleic acid, its
greater hydrophilic property and also, possibly, its greater
affinity for albumin.
The changes in triglyceride fatty acids were not uniform for
all the influences studied. Triglyceride oleate was significantly
lowered by antithyroid therapy in hyperthyroid subjects, but no significant increases could be proved as a result of thyroid
therapy in hypothyroid subjects, thus suggesting that the
increased incorporation of oleic acid into triglyceride fatty acids
may be inhibited in some subjects. Administration of HGH
did not affect triglyceride oleate; observations made during
daily administration of HGH, and in the disease of acromegaly,
suggest that HGH may promote a higher degree of saturation
in triglyceride fatty acids. In subjects with acute myocardial
infarction, the triglyceride fatty acid pattern resembled that of
hyperthyroid subjects. In chronic ischaemic heart disease,
the pattern of triglyceride fatty acids did not differ from
normal. The lack of parallel increases in percentages of
triglyceride oleate with increases in percentages of FFA oleic
acid in patients with chronic ischaemic heart disease suggests
that incorporation of oleic acid into triglyceride fatty acids in
these patients is possibly lower.
In the phospholipid fatty acids, similarly, no common pattern of
changes was noted for the different stimuli studied. The
percentage of phospholipid palmitate decreased significantly
immediately after noradrenaline infusion. Opposite changes
were noted after prolonged fasting. Equally high levels were
observed shortly after myocardial infarction as in ischaemic
patients with hyperphospholipidaemia. The percentage of
phospholipid arachidonate increased significantly following thyroid hormone therapy in hypothyroid subjects. Phospholipid
arachidonate also showed an immediate rise during noradrenaline
infusion. The latter observation supports the concept that
thyroid hormone activity may be mediated through the action
of endogenous catecholamines.
The percentage composition studies on cholesteryl fatty
acids suggest that changes in serum FFA concentrations (due to
HGH daily dose, thyroid hormone and antithyroid therapy, acute
myocardial infarction) produce in most cases directly..related
changes in cholesteryl oleate percentages and inversely - related
changes in cholesteryl linoleate. It is probable that the
increased mobilisation of serum FFA, accompanied by
predominant increases in FFA oleic acid, may promote the
formation of cholesteryl oleate. Cholesteryl arachidonate was
shown to be materially influenced and controlled by thyroid
function: a significant increase in the percentage of
cholesteryl arachidonate occurred after thyroid hormone therapy
in hypothyroid subjects, and a significant decrease occurred
after antithyroid therapy in thyrotoxic subjects; the
thyrotoxic patients had percentage levels of cholesteryl
arachidonate twice as high as those of the hypothyroid patients.
The results agree with the suggestion of Ellefson and Mason
(1964) that thyroid hormones stimulate an increased synthesis
of arachidonic acid from linoleic acid.
An attempt was made to discuss the results in relation to
certain metabolic studies, and to postulate possible
implications of the predominant increase in serum FFA oleic
acid percentage at the time when fatty acids are mobilised
from the storage sites.