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Adipose Tissue�Dr. Emad I H Shaqoura�M.D, M.Sc. Anatomy�Faculty of Medicine, Islamic University-Gaza�

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Headings

Adipose Tissue, Dr. Emad I Shaqoura, Faculty of Medicine-IUG

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Functions of adipose tissue

Types of adipose tissue

White adipose tissue

Brown adipose tissue

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Adipose Tissue

Adipose tissue is a special type of connective tissue in which adipose cells (fat cells) predominate.
These cells can be found isolated or in small groups within the loose or dense irregular C.T.
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.

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Functions of Adipose Tissue

Storage depots for neutral fat (TAG).
Subcutaneous layers of fat 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.
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 hormones that may be carried by the blood to influence distant organs.

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Types of Adipose Tissue

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Adipose Tissue

White Adipose Tissue

Brown Adipose Tissue

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White Adipose Tissue

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White Adipose Tissue

Almost all adipose tissue in adults is of the white type and it is found in and around many organs throughout the body.
Its distribution changes significantly through childhood and adult life and is partly regulated by sex hormones, which control adipose deposition in the breasts and thighs.
The color of freshly dissected white adipose tissue depends on the diet, varying from white to yellow with the amount of carotenoids dissolved in the lipid.

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White Adipose Tissue (cont’d)

It is specialized for long-term energy storage.
Adipocytes of white adipose tissue are spherical when isolated but are polyhedral when closely packed in situ.
Each cell is very large, between 50 and 150 μm in diameter, and contains a single huge droplet of lipid that fills almost the entire cell.
White adipocytes are called unilocular because the triglycerides are stored in this single large droplet.�

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FIGURE 6-1

Figure 6–1 White adipose tissue.

White or unilocular adipose tissue is commonly seen in sections of many human organs. (a) Large white adipocytes (A) are seen in the connective tissue associated with small blood vessels. The fat cells are empty because lipid was dissolved away in slide preparation. Nuclei at the cell membranes are visible in some of the fat cells. X100. H&E.

(b) Large (empty) adipocytes predominate in this typical white adipose tissue, which shows only a small portion of microvasculature. In a single histologic section, nuclei of most very large adipocytes are not included. X100. H&E.

(c) Tissue was fixed here with osmium tetroxide, which preserves lipid (L) and stains it black. Many adipocytes in this slide retain at least part of their large lipid droplets. X440. Osmium tetroxide.

(d) The specimen here was from a young mammal, and the adipocytes marked with asterisks are not yet unilocular, having many small lipid droplets in their cytoplasm, which indicates that their differentiation is not yet complete. The eccentric nuclei of unilocular cells are indicated by arrowheads. X200. PT.

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White Adipose Tissue (cont’d)

Unilocular adipocytes are often empty in standard light microscope preparations.
The cells are sometimes said to have a signet-ring appearance.
Most of the cytoplasm in a white adipocyte surrounds the nucleus and contains mitochondria, a small Golgi apparatus, a few cisternae of RER, and free polyribosomes.
The thin, sub-membranous layer of cytoplasm surrounding the lipid droplet contains cisternae of SER and pinocytotic vesicles.

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White Adipose Tissue (cont’d)

TEM studies reveal that most adipocytes, especially�immature cells, contain minute lipid droplets in addition to the single large droplet seen with the light microscope.
The lipid droplet-cytoplasm interface is reinforced by intermediate filaments of vimentin.
Adipocytes are surrounded by a thin external lamina containing type IV collagen.

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White Adipose Tissue (cont’d)

White adipose tissue is subdivided into incomplete lobules by connective tissue septa containing blood vessels & nerves.
Fibroblasts, macrophages, and other cells make up about half the total number of cells.
Reticular fibers form a fine network that supports individual fat cells and binds them together.
The microvasculature between adipocytes may not always be apparent in tissue sections.

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Medical Application

Unilocular adipocytes can generate benign tumors called lipomas that are relatively common.
Malignant adipose tumors (liposarcomas) occur infrequently.
Fetal lipomas of brown fat are sometimes called hibernomas.

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Storage & Mobilization of Lipids

Sources of TAG stored in white adipose tissue:

Circulating chylomicrons.
Very-low-density lipoproteins (VLDLs).
Local synthesis of free fatty acids and glycerol from glucose.

In adipose tissue both chylomicrons and VLDL are hydrolyzed at the luminal surfaces of blood capillaries by lipoprotein lipase, an enzyme synthesized by the adipocyte and transferred to the capillary cell membrane.

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Storage & Mobilization of Lipids

Free fatty acids enter the adipocyte by both active transport and diffusion.
Within the adipocyte, the fatty acids combine with glycerol phosphate, supplied by glucose metabolism, to again form triglycerides, which are then deposited in the growing lipid droplet.
Mitochondria and SER participate actively in the�process of lipid uptake and storage.
Various hormones can also regulate lipid synthesis and mobilization in adipocytes.

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Storage & Mobilization of Lipids

Insulin:

Stimulates the uptake of glucose into adipocytes.
Increases synthesis of fatty acids from glucose.
Increases the synthesis of lipoprotein lipase.
Inhibits the hormone-sensitive lipase, reducing fatty acid release.

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Increased Lipid Synthesis & Storage

The Net Effect

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Storage & Mobilization of Lipids

Norepinephrine, glucagon and growth hormone:

Promote triglyceride breakdown and release of fatty acids through activation of hormone-sensitive lipase.
Hormone-sensitive lipase breaks down triglycerides at the surface of the stored lipid droplets.

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Increased Lipid Breakdown & Mobilization

The Net Effect

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FIGURE 6-2

Figure 6–2 Lipid storage and mobilization from adipocytes.

Triglycerides are transported by blood and lymph from the intestine and liver in lipoprotein complexes known as chylomicrons (Chylo) and VLDLs. In the capillary endothelial cells of adipose tissue, these complexes 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 that are stored in the lipid droplet until needed.

Norepinephrine from nerve endings stimulates the cyclic AMP (cAMP) system, which activates hormone-sensitive lipase to hydrolyze the stored triglycerides to free fatty acids and glycerol. These substances diffuse into the capillary, where the fatty acids bind albumin for transport throughout the body for use as an energy source.

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Endocrine Function of Adipose Tissue

Adipocytes are the sole source of the polypeptide hormone leptin (Gr. leptos, thin).

Leptin is a “satiety factor” with target cells in the hypothalamus and other organs.
Leptin regulates the appetite under normal conditions.
It also participates in regulating the formation of new adipose tissue.

In addition to leptin, white adipose tissue secretes numerous other cytokines and other factors with paracrine and autocrine activity, including many pro-inflammatory cytokines.

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Medical Application

Leptin was discovered and is well studied in genetically obese mice, but such studies have not led to new treatments for human obesity.

In most obese humans adipocytes produce adequate or excess quantities of leptin, but target cells are not responsive due apparently to:

insufficient or defective receptors
or defective post-receptor signal transduction.

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White Adipose Tissue (cont’d)

Although all white adipose tissue appears histologically similar, differences in gene expression have been noted between visceral deposits (in the abdomen) and subcutaneous deposits of white fat.

Such differences may be important in the�medical risks of obesity; it is well established that increased visceral adipose tissue raises the risk of diabetes and cardiovascular disease whereas increased subcutaneous fat does not.

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White Adipose Tissue (cont’d)

In response to body needs, lipids are mobilized rather uniformly in all parts of the body, although adipose tissue in the palms, soles, and retro-orbital fat pads resists even long periods of starvation.

During starvation, most unilocular adipocytes lose nearly all their fat and become polyhedral or spindle-shaped cells with only very small lipid droplets.

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FIGURE 6-3

Figure 6–3 Development of white and brown fat cells.

Mesenchymal stem cells differentiate as progenitor cells for all types of connective tissue, including preadipocytes. These are initially of at least two types. Preadipocytes developing within the lateral mesoderm of the embryo produce large number of white adipocytes (forming white adipose tissue) and a smaller number of so-called beige adipocytes with cytological features and gene expression patterns of both white and brown adipocytes. White adipocytes are unilocular, with one large lipid droplet occupying most of the cytoplasm. The white adipocyte is usually much larger than that shown here in relation to the other cell types.

Brown adipocytes differentiate from another population of preadipocytes located in paraxial embryonic mesoderm and remain multilocular (having many small lipid droplets) with numerous mitochondria (not shown here). Mitochondrial metabolism of lipid in brown adipocytes releases heat rather than ATP. Cells functioning as brown adipocytes can also develop from beige adipocytes during adaptation to cold temperatures.

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White Adipose Tissue (cont’d)

Humans are born with stores of white adipose tissue, which begin to accumulate at week 14 of gestation and are well developed before birth in both the visceral and subcutaneous compartments.
Proliferation of progenitor cells diminishes by late gestation, and adipose tissue increases mainly by the filing of existing adipocytes until around age 10, followed by a period of new fat cell differentiation which lasts through adolescence.
New adipocyte formation occurs around small blood vessels, where undifferentiated mesenchymal cells are most abundant.

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White Adipose Tissue (cont’d)

Excessive formation of adipose tissue, or obesity, occurs when nutritional intake exceeds energy expenditure, an increasingly common condition in modern, sedentary lifestyles.
Although adipocytes can differentiate from mesenchymal stem cells throughout life, adult-onset obesity mainly involves increased size of existing adipocytes (hypertrophic obesity).

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White Adipose Tissue (cont’d)

Childhood obesity, however, can involve increases in both adipocyte size and numbers due to differentiation of more preadipocytes from mesenchymal stem cells (hyperplastic obesity).
Weight loss after dietary changes is due to reductions in adipocyte volume, but not their overall number.

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Medical Application

Adult-onset obesity is very often associated with age-related metabolic changes and may involve reduced activity of the hormone-sensitive lipases causing reduced fat mobilization out of the cells.
The increased number of adipocytes produced during childhood obesity predisposes an individual to obesity in later life.
Despite claims of various fad diets, there is no evidence that any particular type of caloric restriction is more effective than others; rather, any intake of calories that is lower than the energy expenditure will result in loss of adipose tissue.

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Brown Adipose Tissue

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Brown Adipose Tissue

Brown adipose tissue constitutes 2% to 5% of the newborn body weight.
It is located mainly in the back, neck, and shoulders,�but it is greatly reduced during childhood and adolescence.
In adults it is found only in scattered areas, especially around the kidneys, adrenal glands, aorta, and mediastinum.
The color of brown fat is due to:

Very abundant mitochondria (containing cytochrome pigment) scattered among the lipid droplets of the fat cells.
The number of blood capillaries in this tissue.

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Brown Adipose Tissue (cont’d)

Adipocytes contain many small lipid inclusions and are therefore called multilocular.
The many small lipid droplets, abundant mitochondria, and rich vasculature all help mediate this tissue’s principal function of heat production.

Cells of brown adipose tissue are polygonal and�generally smaller than cells of white adipose tissue; their cytoplasm contains a great number of lipid droplets of various sizes and nuclei are often centrally located.

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FIGURE 6-4

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FIGURE 6-5

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Brown Adipose Tissue (cont’d)

Adipocytes of brown fat are often closely packed around large capillaries.

The tissue is subdivided by connective tissue septa into lobules that are better delineated than the lobules of white adipose tissue.

Cells of this tissue receive direct sympathetic innervation.

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Function of Brown Adipocytes

The main function of the multilocular adipose cells is to produce heat by non-shivering thermogenesis. ��

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Exposure to cold

Increased sympathetic activity & release of NE

Activation of hormone-sensitive lipase

Hydrolysis of TAG & rapid metabolism of FAs for heat production

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Function of Brown Adipocytes

Heat production is increased in these cells because the mitochondria have in their inner membrane much greater levels of a transmembrane protein called thermogenin or uncoupling protein (UCP-1).
Thermogenin permits the backflow of protons previously transported to the intermembranous space without passing through the ATP–synthetase complexes.
Consequently, the energy generated by proton flow dissipates as heat to warm the blood.

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FIGURE 6-3

Figure 6–3 Development of white and brown fat cells.

Mesenchymal stem cells differentiate as progenitor cells for all types of connective tissue, including preadipocytes. These are initially of at least two types. Preadipocytes developing within the lateral mesoderm of the embryo produce large number of white adipocytes (forming white adipose tissue) and a smaller number of so-called beige adipocytes with cytological features and gene expression patterns of both white and brown adipocytes. White adipocytes are unilocular, with one large lipid droplet occupying most of the cytoplasm. The white adipocyte is usually much larger than that shown here in relation to the other cell types.

Brown adipocytes differentiate from another population of preadipocytes located in paraxial embryonic mesoderm and remain multilocular (having many small lipid droplets) with numerous mitochondria (not shown here). Mitochondrial metabolism of lipid in brown adipocytes releases heat rather than ATP. Cells functioning as brown adipocytes can also develop from beige adipocytes during adaptation to cold temperatures.

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Histogenesis of Brown Adipose Tissue

The amount of brown fat is maximal relative to body�weight at birth, when thermogenesis is most needed.
In adults the amount and activity of brown fat are higher in lean individuals.
The number of brown adipocytes increases during cold�adaptation in adults, usually appearing as clusters of multilocular cells in white adipose tissue.
This increase involves:

Reversible shift of beige cells to functional brown adipocytes.
Proliferation and differentiation of new adipocytes from preexisting progenitor cells.
Autonomic nerves promote brown adipocyte differentiation and prevent apoptosis in mature brown fat cells.

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Thank You!