Figure 61

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The Beta Switch Weight Loss Program by Sue Heintze

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Diagram of the development of adipose tissue cells. Like all connective tissue cells, adipocytes are derived from mesenchymal cells (either mesodermally derived mesenchyme or ectomesenchyme derived from the neural crest). Mesenchymal cells give rise to fibroblasts and fibroblast-like cells that are committed to becoming lipoblasts (preadipocytes). Lipoblasts develop an external (basal) lamina and begin to accumulate numerous lipid droplets in their cytoplasm. In white adipose tissue, these droplets fuse to form a single large lipid droplet that ultimately fills the mature cell, compressing the nucleus, cytoplasm, and cytoplasmic organelles into a thin rim around the droplet. In brown adipose tissue, the individual lipid droplets remain separate. (Modified from Henrikson RC, Kaye Gi, Mazurkiewicz JE. NMS Histology. Baltimore: Williams & Wilkins, 1997.)

White adipose tissue begins to form midway through fetal development

The lipoblasts that initially develop along the small blood vessels in the fetus are free of fat. Nevertheless, these cells are committed to becoming fat cells at this early stage; collections of such cells are sometimes called primitive fat organs.

They are characterized by proliferating early lipoblasts and proliferating capillaries. Lipid accumulation in lipoblasts produces the typical morphology of the adipocytes.

Early lipoblasts look like fibroblasts but develop small lipid inclusions and a thin external lamina

TEM studies reveal that early lipoblasts have an elongated configuration, multiple cytoplasmic processes, and abundant endoplasmic reticulum and Golgi membranes. As lipoblastic differentiation begins, smooth-surfaced vesicles increase in number, with a corresponding decrease in rough endoplasmic reticulum (rER). Small lipid inclusions appear at one pole of the cytoplasm. Pinocytotic vesicles and an external lamina also appear.

Midstage lipoblasts become ovoid as lipid accumulation changes the cell dimensions

With further development, the cells assume an oval configuration. The most characteristic feature at this stage is the extensive concentration of smooth vesicles and small lipid droplets around the nucleus and extending toward both poles of the cell. Glycogen particles appear at the periphery of the lipid droplets, and pinocytotic vesicles and basal lamina become more apparent. These cells are designated midstage lipoblasts.

The mature adipocyte is characterized by a single, large lipid inclusion surrounded by a thin rim of cytoplasm

In the late stage of differentiation, the cells increase in size and become more spherical. Small lipid droplets coalesce to form large lipid vacuoles that occupy the central portion of the cytoplasm. Smooth endoplasmic reticulum (sER) is abundant, whereas rER is less prominent. These cells are designated late lipoblasts. Eventually, the lipid mass compresses the nucleus to an eccentric position, producing a signet-ring appearance in hematoxylin and eosin (H&E) preparations. These cells are designated adipocytes or mature lipocytes.

Structure of Adipocytes and Adipose Tissue

Unilocular adipocytes are large cells, sometimes 100 /xm or more in diameter

When isolated, adipocytes are spherical, but they may appear polyhedral or oval when crowded together in adipose tissue. Their large size is due to the accumulated lipid in the cell. The nucleus is flattened and displaced to one side of the lipid mass; the cytoplasm forms a thin rim around the lipid. In routine histologic sections, the lipid is lost through extraction by organic solvents such as xylene; consequently, adipose tissue appears as a delicate mesh-work of polygonal profiles (Fig. 6.2). The thin strand of meshworlc that separates adjacent adipocytes represents the cytoplasm of both cells and the extracellular matrix. The strand is usually so thin, however, that it is not possible to resolve its component parts in the light microscope.

Adipose tissue is richly supplied with blood vessels, and capillaries are found at the angles of the meshwork where adjacent adipocytes meet. Silver stains show that adipocytes are surrounded by reticular fibers (type III collagen), which are secreted by the adipocytes. Special stains also reveal the presence of unmyelinated nerve fibers and numerous mast cells.

The lipid mass in the adipocyte is not membrane bounded

Transmission electron microscopy reveals that the interface between the contained lipid and surrounding cytoplasm of the adipocyte is composed of a 5-nm-thick condensed layer of lipid reinforced by parallel vimentin filaments measuring 5 to 10 nm in diameter. This layer separates the hydrophobic contents of the lipid droplet from the hydrophilic cytoplasmic matrix.

The perinuclear cytoplasm of the adipocyte contains a small Golgi apparatus, free ribosomes, short profiles of rER, microfilaments, and intermediate filaments. Filamentous mitochondria and multiple profiles of sER are also found in the thin rim of cytoplasm surrounding the lipid droplet (Fig. 6.3).

Regulation of Adipose Tissue

The amount of adipose tissue in an individual is determined by expression of the leptin (ob) gene

The recent discovery of the leptin (ob) gene, which encodes a fat-specific mRNA and leptin, has given some insight into the mechanism of energy homeostasis. Human leptin gene expression occurs in mature adipocytes and is highly regulated. Studies of obese individuals show that levels of leptin mRNA in adipose tissue as well as serum levels of leptin are elevated in all types of obesity, regardless of whether it is caused by genetic factors, hypothalamic lesions, or increased efficiency of food utilization. Studies of individuals who have lost weight and those with anorexia nervosa show that leptin mRNA levels in their adipose tissue and serum levels of leptin are significantly reduced. In experimental animal models, the addition of recombinant leptin to obese, leptin-deficient ob/ob mice causes them to reduce their food intake and lose about 30% of their total body weight after 2 weeks of treatment.

Genetic obesity is most likely related to the expression of defective leptin (ob) or leptin receptor genes. This may explain why identical twins usually have the same or close to the same amount of body fat. Even when the amount of body fat in identical twins varies, however, the patterns of distribution are always the same.

Muscle Cells

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