Basic Histology - Text and Atlas 11th ed

ADIPOSE TISSUE: INTRODUCTION

Adipose tissue is a special type of connective tissue in which adipose (L. adeps, fat) cells (adipocytes) predominate. These cells can be found isolated or in small groups within the connective tissue itself; most are found in large aggregates, making up the adipose tissues that are spread throughout the body. Adipose tissue is, in a sense, one of the largest organs in the body. In men of normal weight, adipose tissue represents 15–20% of the body weight; in women of normal weight, it represents 20–25% of body weight.

Adipose tissue is the largest repository of energy (in the form of triglycerides) in the body. The other organs that store energy (in the form of glycogen) are the liver and skeletal muscle. Because eating is a periodic activity and the supply of glycogen is limited, a large store of calories must be mobilized between meals. Because triglycerides are of lower density than glycogen and have a higher caloric value (9.3 kcal/g for triglycerides versus 4.1 kcal/g for carbohydrates), adipose tissue is a very efficient storage tissue. It is in a state of continuous turnover and is sensitive to both nervous and hormonal stimuli. Subcutaneous layers of adipose tissue help to shape the surface of the body, whereas deposits in the form of pads act as shock absorbers, chiefly in the soles and palms.

Because fat is a poor heat conductor, it contributes to the thermal insulation of the body. Adipose tissue also fills up spaces between other tissues and helps to keep some organs in place. Recently, it was observed that adipose tissue secretes various types of molecules that may be carried by the blood to influence distant organs. The two known types of adipose tissue have different locations, structures, colors, and pathological characteristics. Unilocular (common, or yellowadipose tissue is composed of cells that, when completely developed, contain one large central droplet of yellow fat in their cytoplasm. Multilocular (or brown) adipose tissue is composed of cells that contain numerous lipid droplets and abundant brown mitochondria. Both types of adipose tissue have a rich blood supply.

UNILOCULAR ADIPOSE TISSUE

The color of unilocular adipose tissue varies from white to dark yellow, depending on the diet; it is due mainly to the presence of carotenoids dissolved in fat droplets of the cells. Almost all adipose tissue in adults is of this type. It is found throughout the human body except for the eyelids, the penis, the scrotum, and the entire auricle of the external ear except for the lobule. Age and sex determine the distribution and density of adipose deposits.

In the newborn, unilocular adipose tissue has a uniform thickness throughout the body. As the baby matures, the tissue tends to disappear from some parts of the body and to increase in other parts. Its distribution is partly regulated by sex hormones and adrenocortical hormones, which control the accumulation of fat and are largely responsible for male or female body contour.

Unilocular adipose cells are spherical when isolated but are polyhedral in adipose tissue, where they are closely packed. Each cell is between 50 and 150 m in diameter. Because lipid droplets are removed by the alcohol and xylol used in routine histological techniques, each cell appears in standard microscope preparations as a thin ring of cytoplasm surrounding the vacuole left by the dissolved lipid droplet—the signet ring cell. Consequently, these cells have eccentric and flattened nuclei (Figure 6–1). The rim of cytoplasm that remains after removal of the stored triglycerides (neutral fats) may rupture and collapse, distorting the tissue structure.

Figure 6–1.

 

Photomicrograph of unilocular adipose tissue of a young mammal. Arrowheads show nuclei of adipocytes (fat cells) compressed against the cell membrane. Note that although most cells are unilocular, there are several cells (asterisks) with small lipid droplets in their cytoplasm, an indication that their differentiation is not yet complete. Pararosaniline–toluidine blue (PT) stain. Medium magnification.

The thickest portion of the cytoplasm surrounds the nucleus of these cells and contains a Golgi complex, mitochondria, poorly developed cisternae of the rough endoplasmic reticulum, and free polyribosomes. The rim of cytoplasm surrounding the lipid droplet contains cisternae of smooth endoplasmic reticulum and numerous pinocytotic vesicles. Electron microscopic studies reveal that each adipose cell usually possesses minute lipid droplets in addition to the single large droplet seen with the light microscope; the droplets are not enveloped by a membrane but show many vimentin intermediate filaments in their periphery. Each adipose cell is surrounded by a basal lamina.

Unilocular adipose tissue is subdivided into incomplete lobules by a partition of connective tissue containing a rich vascular bed and network of nerves. Reticular fibers form a fine interwoven network that supports individual fat cells and binds them together.

Although blood vessels are not always apparent in tissue sections, adipose tissue is richly vascularized. If the amount of cytoplasm in fat cells is taken into consideration, the ratio of blood volume to cytoplasm volume is greater in adipose tissue than in striated muscle.

Storage & Mobilization of Lipids

The unilocular adipose tissue is a large depot of energy for the organism. The lipids stored in adipose cells are chiefly triglycerides, ie, esters of fatty acids and glycerol. Fatty acids stored by these cells have their origin in dietary fats that are brought to adipose tissue cells in the form of chylomicron triglycerides, in triglycerides synthesized in the liver and transported to adipose tissue in the form of very low-density lipoproteins (VLDL), and by the synthesis of free fatty acids and glycerol from glucose to form triglycerides in adipose cells.

Chylomicrons (Gr. chylos, juice, + micros, small) are particles up to 3 m in diameter, formed in intestinal epithelial cells and transported in blood plasma and mesenteric lymph. They consist of a central core, composed mainly of triglycerides and a small quantity of cholesterol esters, surrounded by a stabilizing monolayer consisting of apolipoproteins, cholesterol, and phospholipids. VLDL have proportionately more lipid in their surface layer because they are smaller (providing a greater surface-to-volume ratio), have different apolipoproteins at the surface, and contain a higher proportion of cholesterol esters to triglycerides than do chylomicrons. Chylomicrons and VLDL are hydrolyzed at the luminal surfaces of blood capillaries of adipose tissue by lipoprotein lipase, an enzyme synthesized by the adipocyte and transferred to the capillary cell membrane. Free fatty acids enter the adipocyte by mechanisms that are not completely understood. Both an active transport system and free diffusion seem to be involved. The numerous pinocytotic vesicles seen at the surfaces of adipocytes are probably not involved. The fatty acids cross the following layers (in order) in passing from the endothelium into the adipose cell: (1) capillary endothelium, (2) capillary basal lamina, (3) connective tissue ground substance, (4) adipocyte basal lamina, and (5) adipocyte plasma membrane. The movement of fatty acids across the cytoplasm into the lipid droplet is incompletely understood but may utilize specific carrier proteins (Figure 6–2). Within the adipocyte, the fatty acids combine with glycerol phosphate, an intermediate product of glucose metabolism, to form triglyceride molecules. These are then deposited in the triglyceride droplets. Mitochondria and smooth endoplasmic reticulum are organelles that participate actively in the process of lipid uptake and storage.

Figure 6–2.

 

The process of lipid storage and release by the adipocyte. Triglycerides are transported in blood from the intestine and liver by lipoproteins known as chylomicrons (Chylo) and very low-density lipoproteins (VLDL). In adipose tissue capillaries, these lipoproteins are partly broken down by lipoprotein lipase, releasing free fatty acids and glycerol. The free fatty acids diffuse from the capillary into the adipocyte, where they are reesterified to glycerol phosphate, forming triglycerides. These resulting triglycerides are stored in droplets until needed. Norepinephrine from nerve endings stimulates the cyclic AMP (cAMP) system, which activates hormone-sensitive lipase. Hormone-sensitive lipase hydrolyzes stored triglycerides to free fatty acids and glycerol. These substances diffuse into the capillary, where free fatty acids are bound to the hydrophobic moiety of albumin for transport to distant sites for use as an energy source.

Adipose cells can synthesize fatty acids from glucose, a process accelerated by insulin. Insulin also stimulates the uptake of glucose into the adipose cells and increases the synthesis of lipoprotein lipase.

Stored lipids are mobilized by humoral and neurogenic mechanisms, resulting in the liberation of fatty acids and glycerol into the blood. Triglyceride lipase, an enzyme known as hormone-sensitive lipase, is activated by adenylate cyclase when the tissue is stimulated by norepinephrine. Norepinephrine is liberated at the endings of the postganglionic sympathetic nerves present in adipose tissue. The activated enzyme breaks down triglyceride molecules, which are located mainly at the surface of the lipid droplets. The relatively insoluble fatty acids are transported in association with serum albumin to other tissues of the body, whereas the more soluble glycerol remains free and is taken up by the liver.

Growth hormone, glucocorticoids, prolactin, corticotropin, insulin, and thyroid hormone also have roles at various stages in the metabolism of adipose tissue.

Adipose tissue also functions as a secretory organ. It synthesizes several molecules that are carried by the blood or remain attached to the endothelium of capillaries around the adipose cells (eg, the lipoprotein lipase). The most extensively studied substance produced by adipose cells is leptin, a protein made of 164 amino acids. Several cells in the brain and other tissues have receptors for leptin. This molecule participates in the regulation of the amount of adipose tissue in the body and in food ingestion. It acts mainly in the hypothalamus to decrease food intake and increase energy consumption.

The sympathetic division of the autonomic nervous system richly innervates both unilocular and multilocular adipose tissues. In unilocular adipose tissue, nerve endings are found only in the walls of blood vessels; the adipocytes are not directly innervated. Release of the neurotransmitter norepinephrine activates the hormone-sensitive lipase described above. This innervation plays an important role in the mobilization of fats.

In response to body needs, lipids are not mobilized uniformly in all parts of the body. Subcutaneous, mesenteric, and retroperitoneal deposits are the first to be mobilized, whereas adipose tissue in the hands, feet, and retroorbital fat pads resists long periods of starvation. After such periods of starvation, unilocular adipose tissue loses nearly all its fat and contains polyhedral or spindle-shaped cells with very few lipid droplets.

MEDICAL APPLICATION

Obesity in adults may result from an excessive accumulation of fat in unilocular tissue cells that have become larger than usual (hypertrophic obesity). An increase in the number of adipocytes causes hyperplastic obesity.

Histogenesis of Unilocular Adipose Tissue

Adipose cells develop from mesenchymally derived lipoblasts. These cells have the appearance of fibroblasts but are able to accumulate fat in their cytoplasm. Lipid accumulations are isolated from one another at first but soon fuse to form the single larger droplet that is characteristic of unilocular tissue cells (Figure 6–3).

Figure 6–3.

 

Development of fat cells. Undifferentiated mesenchymal cells are transformed into lipoblasts that accumulate fat and thus give rise to mature fat cells. When a large amount of lipid is mobilized by the body, mature unilocular fat cells return to the lipoblast stage. Undifferentiated mesenchymal cells also give rise to a variety of other cell types, including fibroblasts. The mature fat cell is larger than that shown here in relation to the other cell types.

The human being is one of the few mammals born with fat stores, which begin to accumulate at week 30 of gestation. After birth, the development of new adipose cells is common around small blood vessels, where undifferentiated mesenchymal cells are usually found.

It is believed that during a finite postnatal period, nutritional and other influences can result in an increase in the number of adipocytes, but the cells do not increase in number after that period. They accumulate more lipids only under conditions of excess caloric intake (overfeeding). This early increase in the number of adipocytes may predispose an individual to hyperplastic obesity in later life.

MULTILOCULAR ADIPOSE TISSUE

Multilocular adipose tissue is also called brown fat because of its color, which is due to both the large number of blood capillaries in this tissue and the numerous mitochondria (containing colored cytochromes) in the cells. Compared with unilocular tissue, which is present throughout the body, brown adipose tissue has a more limited distribution. (Because it is more abundant in hibernating animals, it was at one time called the hibernating gland.)

In rats and several other mammals, multilocular adipose tissue is found mainly around the shoulder girdle. In the human embryo and newborn, this tissue is encountered in several areas and remains restricted to these locations after birth (Figure 6–4). In humans, this tissue appears to be important mainly in the first months of postnatal life, when it produces heat and thus protects the newborn against cold. It is greatly reduced in adulthood.

Figure 6–4.

 

Distribution of adipose tissue. In a human newborn, multilocular adipose tissue constitutes 2–5% of the body weight and is distributed as shown. The black areas indicate multilocular adipose tissue; shaded areas are a mixture of multilocular and unilocular adipose tissue. (Modified, redrawn, and reproduced, with permission, from Merklin RJ: Growth and distribution of human fetal brown fat. Anat Rec 1974;178:637.)

 

Multilocular tissue cells are polygonal and smaller than cells of unilocular adipose tissue. Their cytoplasm contains a great number of lipid droplets of various sizes (Figures 6–5 and 6–6), a spherical and central nucleus, and numerous mitochondria with abundant long cristae.

Figure 6–5.

 

Photomicrograph of multilocular adipose tissue (lower portion) with its characteristic cells containing central spherical nuclei and multiple lipid droplets. For comparison, the upper part of the photomicrograph shows unilocular tissue. PT stain. Medium magnification.

 

Figure 6–6.

 

Multilocular adipose tissue. Note the central nucleus, multiple fat droplets, and abundant mitochondria. A sympathetic nerve ending is shown at the lower right.

Multilocular adipose tissue resembles an endocrine gland in that its cells assume an almost epithelial arrangement of closely packed masses associated with blood capillaries. This tissue is subdivided by partitions of connective tissue into lobules that are better delineated than are unilocular adipose tissue lobules. Cells of this tissue receive direct sympathetic innervation.

Function of the Multilocular Adipose Cells

The main function of the multilocular adipose cells is to produce heat. The physiology of multilocular adipose tissue is best understood in the study of hibernating species.

In animals ending their hibernation period, or in newborn mammals (including humans) that are exposed to a cold environment, nerve impulses liberate norepinephrine into the tissue. This neurotransmitter activates the hormone-sensitive lipase present in adipose cells, promoting hydrolysis of triglycerides to fatty acids and glycerol. Liberated fatty acids are metabolized, with a consequent increase in oxygen consumption and heat production, elevating the temperature of the tissue and warming the blood passing through it. Heat production is increased, because the mitochondria in cells of this tissue have a transmembrane protein called thermogenin in their inner membrane. Thermogenin permits the backflow of protons previously transported to the intermembranous space without passing through the adenosine triphosphate (ATP)-synthetase system in the mitochondrial globular units. Consequently, the energy generated by proton flow is not used to synthesize ATP but is dissipated as heat. Warmed blood circulates throughout the body, heating the body and carrying fatty acids not metabolized in the adipose tissue. Other organs use these fatty acids.

Histogenesis of Multilocular Adipose Tissue

Multilocular adipose tissue develops differently from unilocular tissue. The mesenchymal cells that constitute this tissue resemble epithelium (thus suggesting an endocrine gland) before they accumulate fat. Apparently, there is no formation of multilocular adipose tissue after birth, and one type of adipose tissue is not transformed into another.

Tumors of Adipose Tissues

MEDICAL APPLICATION

Unilocular adipocytes can generate very common benign tumors called lipomas. Malignant adipocyte-derived tumors (liposarcomas) are not frequent in humans.

REFERENCES

Angel A et al (editors): The Adipocyte and Obesity: Cellular and Molecular Mechanisms. Raven Press, 1983. 

Forbes GB: The companionship of lean and fat. Basic Life Sci 1993;60:1. [PMID: 8110085] 

Matarese G: Leptin and the immune system: how nutritional status influences the immune response. Eur Cytokine Netw 2000;11:7. [PMID: 10705294] 

Matson CA et al: Leptin and regulation of body adiposity. Diabetes Rev 1999;4:488. 

Napolitano L: The differentiation of white adipose cells: an electron microscope study. J Cell Biol 1963;8:663. 

Nedergaard J, Lindberg O: The brown fat cell. Int Rev Cytol 1982;4:310. 

Schubring C et al: Leptin, the ob gene product, in female health and disease. Eur J Obstet Gynecol Reprod Biol 2000;88:121. [PMID: 10690668] 



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