Molecular medicine-Regulatory Mechanisms that Balance Lipid Storage and Utilization

The pathways that promote FFA uptake
and esterification to triglyceride are
strongly regulated by hormones, particularly
insulin. Insulin strongly promotes the
synthesis of LPL whose expression coincides
with the peak of triglyceride absorption.
Insulin and chylomicrons also stimulate
the secretion of acylation stimulation
protein – a protein made by adipocytes that
strongly promotes triglyceride synthesis.
Insulin also promotes de novo fatty acid
synthesis from glucose by stimulating glucose
uptake and the expression of lipogenic
enzymes.
Fatty acids, derived from adipose tissues,
are an important energy source during
fasting, exercise, and stress. As mentioned
above, the overall rate of lipolysis is
largely governed by the relative activation
of PKA. The activity of PKA is governed
by cAMP levels, which in turn are controlled
by receptors coupled positively (beta
adrenergic, glucagon, ACTH) or negatively
(adenosine, niacin, alpha2, adrenergic) to
adenylyl cyclase. In addition, insulin regulates
adipocyte cAMP levels by activating
phosphodiesterase PDE3b that degrades
cAMP. The nature of the pathways controlling
lipolysis depends on physiological
circumstances. Lipolysis, in response to
stress and exercise, is highly dependent on
the activity of the sympathetic innervation
of adipose tissue as well as the release of
epinephrine from the adrenal gland. During
fasting, lipolysis does not depend on
neural activity, but rather appears to result
from decline in insulin that provides tonic
activation of PDE3b.