Adipose Cell Ultrastructure. Storage and Release of Lipid

Each adipocyte consists of a large lipid droplet surrounded by a thin layer of cytoplasm, thus forming a ringlike unilocular structure. Electron microscopy reveals subcellular organelles along with a variety of lipid droplets plus an extensive system of membranous organelles within the cell’s cytoplasm. The central lipid droplet is surrounded by a fenestrated envelope.

Cytoplasmic lipid droplets, occurring separately or as aggregates, are also frequently surrounded by fenestrated envelopes but may occur without them. The system of membranes stems from invaginations of the cell membrane. There are features such as vesicles, simple and vesiculated vacuoles, a smooth-surfaced endoplasmic reticulum, and Golgi complexes.

The mature white adipocyte is roughly 95% stored lipid (e.g., triglyceride) by weight. The cell is active metabolically, although the metabolic rate (e.g., energy consumption) of adipose tissue relative to many other tissues is low. Unfortunately, little is known about the cells function in relation to the fine structure revealed by electron microscopy.

Usually, the perinuclear cytoplasm is thin and the nucleus flattened. Fenestrations that divide the flattened envelope vary considerably in dimension with cytoplasm filling each fenestration and separating the envelope from the stored lipid. The contained lipid droplets vary in size, structure, and distribution. Three classes of inclusions have been identified within the adipocytes cytoplasm: lipid droplets of moderate and relatively uniform size, lipid droplets not associated with a fenestrated envelope (generally small and in groups), and packed aggregates of very small droplets.

An additional ultrastructural feature is the system of membranous organelles. A system of cytoplasmic vesicles and vacuoles appear to invaginate from the membranous structure that surrounds the cytoplasm of the adipose cell. A basement membrane also surrounds each cell. Distortions of the cell membrane (invaginations) occur at irregular intervals and range from slight indentations to developed vesicles connected to the membrane by a narrow neck. Rosettelike invaginations (i.e., complexes of fused vesicles) are observed.

The structural similarities among invaginations, rosettes, small vacuoles, and other vesicles suggest a common origin from the cell membrane. Nevertheless, technical artifacts may produce some of the observed diversity. The ultrastructure of the adipocyte may be related to the demand of a bidirectional transport and metabolism of fatty acids and triglyceride synthesis and mobilization. Presumably, the adipocyte is prepared to respond rapidly to lipogenic (movement in) or lipolytic (movement out) hormones that control movement of the lipid transport molecules.

Storage and Release of Lipid. Circulating lipoprotein triglyceride is the main precursor of lipid within the adipocyte, and assimilation of triglyceride requires hydrolysis by the enzyme lipoprotein lipase (LPL). The activity of LPL in adipose tissue is relatively high in the fed state and is less in the fasted or insulin-deficient state. Thus, assimilation of stored lipid occurs when circulating triglycerides, in the blood are abundant.

The hormone gastric inhibitory peptide, secreted after glucose or fat ingestion, increases LPL activity. Insulin may act on the adipocyte by enhancing LPL synthesis. Released LPL migrates to the adjacent capillaries and binds to endothelial cells where it exerts lipolytic action. At present, it is unknown whether or not the enzyme turnover associated with capillary endothelium is a function of lipoprotein triglyceride flux through the capillary bed.

The distribution of lipoprotein triglyceride in tissues such as the myocardium, skeletal muscle, and adipose tissue may well be a function of mutational state and timing of meals rather than diurnal variations of adipocyte LPL, but quantitation of such distribution has not been accomplished.

Adipose tissue adapts to positive caloric balance by the hydrolysis of lipoprotein triglyceride to fatty acids through the capillary endothelium into the adipocytes, where the new triglyceride is stored. The entry of fatty acids into adipocytes may well involve a saturable transport system with diffusion coming into play at high concentrations of unbound fatty acids. Some of the crucial enzymes involved in triglyceride synthesis are associated with the processes of phosphorylation-dephosphorylation and insulin induction. Coordination of these several processes is quite important but poorly understood (e.g., the localization of gene coding of the enzymatic proteins remains to be accomplished).

At least three hormones exhibit antilipolytic properties—insulin, E-prostaglandins, and the α2- receptor-specific catecholamines. Insulin is probably the most important hormone in the mobilization of stored lipid. Insulin has several known effects including inhibition of adenylate cyclase and activation of soluble cyclic adenosine monophosphate phosphodiesterase and may directly block free fatty-acid efflux. Mediators of lipid flux include AMP-dependent kinase and phosphoprotein phosphatase. The alteration of cyclic AMP concentrations or phosphatase activation may result. The inhibition of lipolysis by α2-agonists occurs through inhibition of adenylate cyclase.

The respective importance of these regulatory processes remains unknown in vivo. Suffice it to say that adipocytes are usually exposed to a variety of signals that carry contradictory messages. The intake of food, for example, induces both insulin and catecholamine release and exposure to lipolytic agents produces production of prostaglandins along with lipolysis. The integrated responses may well change as adipocytes enlarge or shrink or display different characteristics in diverse storage areas.