Molecular medicine-Absorption and Storage of Circulating Lipid

Energy is stored in adipocytes in the form
of triglycerides and is mainly derived from
dietary fat, and de novo biogenesis from
liver and within adipose tissue. Although
human adipose tissue is capable of synthesizing
lipid de novo, most triglycerides that
accumulate in the tissue are derived directly
or indirectly from dietary fat. Dietary
fat is digested in the gut and repackaged as
chylomicrons that are delivered to the systemic
circulation via the lymphatics. The
liver also plays a major role in the production
and packaging of lipids in the form
of various lipoproteins that are targeted
for utilization in various target tissues,
including adipose tissue.
A major mechanism for clearing
chylomicrons and very low density
lipoproteins (VLDL) from the circulation
is through the action of lipoprotein lipase
(LPL). As mentioned above, adipocytes
express LPL, which is released and
targeted to the capillary endothelium
(Fig. 1). There, LPL acts on circulating
chylomicrons and VLDL, hydrolyzing the
neutral lipid core and releasing free fatty
acids. The free fatty acids that are released
can cross cell membranes and enter
Adipocytes 5
Nucleus
HSL
LPL
LPL
TG
Adipocyte
Lipid
droplet
(TG)
Capillary
TG-rich
lipoprotein
LPL
Fed state – High insulin
Nucleus
HSL
LPL
Adipocyte
Lipid
droplet
(TG)
Capillary
cAMP
+
Catecholamines
FA
FA
FA
Albumin
Fasted state – Low insulin
Fig. 1 Lipid storage and mobilization in adipocytes during fed and fasted states. See text for
details. Flux of dietary lipid from circulating lipoprotein particles to the adipocyte lipid droplet
is shown in green. Flux of stored lipid from adipocyte back into circulation shown in blue. TG,
triglyceride; FA, fatty acid; HSL, hormone-sensitive lipase; LPL, lipoprotein lipase. (See color
plate p. xxii).
adipocytes directly.Additionally, fatty acids
can enter adipocytes via transport proteins,
such as CD36 and FATP1. The flow
of free fatty acids is governed by its
concentration gradient. In the case of
adipocytes, free fatty acid (FFA) that enter
cells quickly encounter proteins that bind
FFA, such as members of the fatty acid
binding protein (FABP) family involved
in cytoplasmic transport, or enzymes
involved in metabolic conversion into
triglyceride, such as long chain acyl-
CoA synthase, thereby maintaining a
significant concentration gradient.