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Morphology and Development of Adipose Tissue

In adult mammals, the major bulk of adipose tissue is a loose association of lipid-filled cells called adipocytes, which are held in a framework of collagen fibers.  In addition to adipocytes, adipose tissue contains stromal-vascular cells including fibroblastic connective tissue cells, leukocytes, macrophages, and pre-adipocytes (not yet filled with lipid), which contribute to structural integrity.


The lipid droplets in adipose tissue can be unilocular and/or multilocular.  Unilocular cells contain a single large lipid droplet which pushes the cell nucleus against the plasma membrane, giving the cell a signet-ring shape (Figure 1).  Unilocular cells, characteristic of white adipose tissue, range in size from 25 to 200 microns.  Mitochondria are found predominately in the thicker portion of the cytoplasmic rim near the nucleus.  The large lipid droplet does not appear to contain any intracellular organelles.  Multilocular cells, typically seen in brown adipose tissue, contain many smaller lipid droplets.  A cell in brown adipose tissue may reach a diameter of 60 microns and the lipid droplet within the cell may reach 25 microns in diameter.  As mentioned above, the brown color of this tissue is derived from the cells' rich vascularization and densely packed mitochondria.  These mitochondria vary in size and may be round, oval, or filamentous in shape.
Approximately 60 to 85% of the weight of white adipose tissue is lipid, with 90-99% being triglyceride.  Small amounts of free fatty acids, diglyceride, cholesterol, phospholipid and minute quantities of cholesterol ester and monoglyceride are also present.  In this lipid mixture, six fatty acids make up approximately 90% of the total, and these are myristic, plamitic, palmitoleic, stearic, oleic, and linoleic.  Varying the composition of your diet can vary the fatty acid profile in adipose tissue.  The remaining weight of white adipose tissue is composed of water (5 to 30%) and protein (2 to 3%).
White adipose tissue is not as richly vascularized as brown adipose tissue, but each adipocyte in white adipose tissue is in contact with at least one capillary.  This blood supply provides sufficient support for the active metabolism, which occurs in the thin rim of cytoplasm surrounding the lipid droplet.  Blood flow to adipose tissue varies depending upon body weight and nutritional state, with blood flow increasing during fasting.
Adipocytes are considered to originate from fibroblast-like precursor cells that differentiate into adipocytes under the appropriate stimulatory conditions (described below).  The precursor cells do not possess any morphological or enzymatic marker that can be used to determine whether they will become adipocytes.  The criteria used to identify adipocytes depends upon lipid accumulation within the cell after proliferation has stopped, making early identification of adipocytes difficult.
The size of adipose tissue mass is a function of both adipocyte number and size.  An increase in adipose tissue mass can occur by hyperplastic growth, which is an increase in the number of adipocytes.  This increase in number occurs primarily by mitotic activity in precursor cells.  Adipose tissue mass can also increase by hypertrophic growth, which is an increase in the size of adipocytes.  This increase in size occurs primarily by lipid accumulation within the cell.  Growth of this tissue in the rat occurs in well-defined stages.  From birth to 4 weeks of age, adipose tissue growth is hyperplastic.  Overfeeding a rat during this period can lead to permanent increases in body weight and fat cell number.  From 4 to 14 weeks of age both adipocyte hypertrophy and hyperplasia occur.  Following 14 weeks of age, adipose tissue growth occurs predominantly by adipocyte hypertrophy. 
The developmental sequence of adipose tissue in humans is less well defined.  In contrast to most neonates, the human neonate is born relatively fat.  Two periods of hyperplastic growth are probably during the third trimester of pregnancy and just prior to and during puberty.  
Contrary to earlier belief, hyperplastic growth can also occur in adulthood (in both humans and rats).  When adipocytes fill with lipid and get to a critical size, precursor cells are stimulated to differentiate, and an increase in adipocyte number results.  This critical size probably does not occur with moderate overfeeding unless the overfeeding is of long duration.  In addition, there are probably individual differences in the size that will result in new adipocyte formation.  Once new adipocytes are formed, they remain throughout life and only a reduction in size of the cell is possible.  This increased number of adipocytes has far-reaching consequences for the treatment and prevention of obesity

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