Histology
Chapter 6
Adipose Tissue
 Adipose Tissue
o adipocytes – fat-storing cells
 isolated or in small groups – in loose or dense
irregular connective tissue
 large aggregates as adipose tissue (“fat”) – in
many organs and body regions
o 15%-20% of the body weight in men, more in women
o Storage depots for neutral fats
 Triglycerides – long-chain fatty acyl esters of
glycerol
o Key regulators of body’s overall energy metabolism
 Two properties of triglyceride
 preferred form of nutrient storage against
fluctuating availability and energy demands
 Adipocytes specialize in concentrating
triglycerides as lipid droplets
1. Insoluble in water – can be concentrated with no
adverse osmotic effects on cells
2. Caloric density of triglycerides (9.3 kcal/g) – twice
that of proteins or carbohydrates, including glycogen
making these simple lipids the most efficient means
of storing calories
 Functions
o Adipocytes – metabolically active cells
 respond to both NERVOUS & HORMONAL
stimuli
 release hormones and various other important
substances
 adipose tissue – ENDOCRINE TISSUE at the
center of nutritional homeostasis
o Adipose tissue – rich in fat
 conducts heat POORLY and provides thermal
insulation for the body
o Adipose tissue – fills spaces between other tissues
 helping to keep some organs in place
o Subcutaneous layers of adipose tissue – help shape
the body surface, and cushion regions subject to
repeated mechanical stress (palms, heels & toe pads)
 Acts as shock absorbers
 Two major types of adipose tissue:
1. White Adipose Tissue
o more common type specialized for fat storage
o consists of cells each containing one large
cytoplasmic droplet of whitish-yellow fat
2. Brown Adipose Tissue
o Contains cells with multiple lipid droplets
interspersed among abundant mitochondria,
which helps give this tissue a darker appearance
6.1 White Adipose Tissue
 White Adipose Tissue
o Function:
 specialized for relatively long-term energy
storage
o Shape of adipose:
 spherical: isolated
 polyhedral: closely packed in situ
o between 50 and 150 µm in diameter
o UNILOCULAR – with a single huge droplet of lipid
filling almost the entire cell
Because lipid is removed from cells by xylene, or other solvent used in routine
histological techniques, unilocular adipocytes are often empty in standard
light microscopy
 Adipocytes in White Adipose Tissue
o (sometimes) signet-ring appearance – droplet
displacing and flattening the nucleus against the
membrane
o membrane and tthin rim of cytoplasm that remains
after dissolution of the stored lipid may shrink,
collapse or rupture, distorting cell and tissue
structure
o Most cytoplasmic organelles – near the peripheral
nucleus
 mitochondria, a small Golgi Apparatus, a few
cisternae of RER and free polyribosomes
o thin submembranous layer of cytoplasm surrounding
the lipid droplet contains the cisternae of smooth ER
(SER) and pinocytic vesicles
o surrounded by thin external lamina
 contains type IV collagen
 TEM studies
o immature cells contain minute lipid droplets in
addition to the single large droplet
o vimentin (intermediate filaments) – reinforced the
lipid droplet-cytoplasm interface
 White fat is subdivided into incomplete lobules by
partitions of connective tissue containing a vascular bed
and nerve network
- Fibroblast, macrophages, and other cells typically
comprise about half the total cell number in white
adipose tissue
Reticular fibers form a fine interwoven network that supports
individual fat cells and binds them together, and the
microvasculature between adipocytes may not always be apparent
in tissue sections
 The distribution of white adipose tissue changes significally
through childhood and adult life and is partly regulated by
sex hormones controlling adipose deposition in breasts
and thighs.
  The color of freshly dissected white adipose tissue
depends on diet, varying from white to yellow with the
amount of carotenoids dissolved in the lipid.
Storage and mobilization of lipids
White adipocytes can store triglycerides derived from three sources:
1. Dietary fats brought via the circulation as chylomicrons
2. Lipids synthesized in the liver and transported in blood
with very-low-density lipoproteins (VLDLs)
3. Free fatty acids and glycerol synthesized by the adipocytes
Chylomicrons
- Particles of variable size, up to 1200 nm in diameter
- Formed from ingested lipids in epithelial cells lining the
small intestine and transported in the blood and lymph
- Consist of a core containing mainly triglycerides,
surrounded by a stabilizing monolayer of phospholipids,
cholesterol and several apolipoproteins
VLDLs
- Smaller complexes (30-80 nm, providing a greater surface
to volume ratio) of similar lipid and protein composition
to chylomicrons but are synthesized from lipids in liver
cells
Levels of circulating lipoproteins are routinely measured in
clinical tests for blood lipids, after fasting to allow depletion of
chylomicrons
- Varying levels of apoproteins and triglycerides in the
complexes allow their categorization according to
density, from VLDL to high-density lipoproteins (HDL)
In adipose tissue, BOTH CHYLOMICRONS and VLDLs are
hydrolyzed at the luminal surfaces of blood capillaries by
Lipoprotein lipase, an enzyme synthesized by adipocytes and
transferred to the capillary cell membrane. Free fatty acids then
enter the adipocytes by both active transport and diffusion. Within
the adipocytes, the fatty acids combine with glycerol phosphate,
supplied by glucose metabolism., to again form triglycerides, which
are then deposited in the growing lipid droplet.
Insulin – stimulates glucose uptake by adipocytes and accelerates its
conversion into triglycerides, and the production of lipoprotein
lipase
 When adipocytes are stimulated by nerves or various
hormones, stored lipids are mobilized and cells release
fatty acids and glycerol
Norepinephrine – released in the adrenal gland and post ganglionic
sympathetic nerves in adipose tissue activates a hormone-sensitive
lipase that breaks down triglycerides at the surface of stored lipid
droplets. This lipase activity is also stimulated by growth hormone
(GH) from the pituitary gland.
The free fatty acids diffuse across the membranes of the
adipocyte and the capillary endothelium and bind the protein
albumin in blood for transport throughout the body.
 The more water-soluble glycerol, remains free in blood
and is taken up by the liver.
Insulin – inhibits the hormone sensitive lipase, reducing fatty acid
release and also stimulates enzymes for lipid synthesis. Besides
insulin and GH, other peptide hormones also cooperate in regulating
lipid synthesis and mobilization in adipocytes.
Hormonal activity of white adipocytes themselves include
production of 16-kDa polypeptide hormone Leptin – a “satiety
factor” with target cells in the hypothalamus, other brain regions
and peripheral organs which helps regulate the appetite under
normal conditions and participates in regulating the formation of
new adipose tissue.
Although white adipose tissue associated with different
organs 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. The release of visceral fat products directly to the portal
circulation and liver may also influence the medical importance of
this form of obesity.
In response to body needs, lipids are mobilized rather than
uniformly form white adipocytes in all parts of the body, although
adipose tissue in palms, soles and fat pads behind the eyes resist
even long periods of starvation.
 During starvation, adipocytes can loose nearly all their fat
and become polyhedral or spindle-shaped cells with only
very small lipid droplets.
Histogenesis of White Adipose Tissue
Like other connective tissue, adipocytes develop from
mesenchymal stem cells. Adipose development first produces
preadipocytes, which look rather like larger fibroblast with
cytoplasmic lipid droplets. Initially, the droplets of white adipocytes
are isolated from one another but soon fuse to form the single large
droplet.
White adipocytes develop together with a smaller
population of cells – Beige adipocytes, which remain within adipose
tissue and have histological and metabolic features generally
intermediate between white and brown adipocytes. With
adaptation to cold temperatures beige adipocytes, change
reversibly, forming many more small lipid droplets, adopting a gene
profile more like that of brown fat, and begin to release heat.
Humans are born with stores of white adipose tissue,
which begin to accumulate by 14th week of gestation. Both visceral
and subcutaneous fat is well-developed before birth. Proliferation of
progenitor cells diminishes by late gestation, and adipose tissue
increases mainly by filling 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.
Excessive adipose accumulation or obesity, occurs when
nutritional intake exceeds expenditure, an increasingly common
condition in modern, sedentary lifestyles. Although adipocytes can
differentiate from mesenchymal stem cells throughout life, adult-
onset obesity mainly involves increasing the size of existing
adipocytes (hypertrophy). Childhood obesity in contrast, involves
increase in both adipocyte size and numbers due to the
differentiation of more preadipocytes from mesenchymal cells
(hyperplasia). Weight loss after dietary changes is due to reductions Brown tissue also develops from the mesenchyme, but
in adipocyte volume, but not their overall number. involves preadipocytes in a different embryonic location (paraxial)
from those producing white adipose tissue. Brown adipoctyes also
3. Brown Adipose Tissue emerge earlier than white fat during fetal development.
- Contains cells with multiple lipid droplets interspersed
among abundant mitochondria, which helps give this  In humans the amount of brown fat is maximal relative to
tissue a darker appearance the body weight at birth, when the thermogenesis is most
- Release heat and function the warm blood needed and partially disappears by involution and
- Constitutes 2%-5% of the newborn body weight, located apoptosis during childhood. In adults the amount and
mainly the back, neck and shoulders, but it is greatly activity of brown fats are higher in lean indiviuduals.
reduced during childhood and adolescence.
- In adult, it is found only in scattered areas, especially The number of brown adipocytes increased during cold
around the kidneys, adrenal glands, aorta and adaptation, usually appearing as clusters of multilocular cells in
mediastinum. The color of brown fat is due to both the white adipose tissue. As indicated earlier, this increase involves the
very abundant mitochondria (containing cytochrome reversible shift of beige cells to functional brown adipocytes, but
pigment) scattered among the lipid droplets of fat cells may also include proliferation and differentiation of new adipocytes
and the large number of blood capillaries in this tissue. from preexisiting progenitor cells. Besides stimulating thermogenic
- Contain many small lipid inclusions and are therefore activity, autonomic nerves also promote brown adipocyte
called MULTILOCULAR differentiation and prevent apoptosis in mature brown fat cells.
- the small lipid droplets, abundant mitochondria and rich
vasculature all mediate the tissue’s principal function of
heat production and warming the blood
- cells are polygonal and generally smaller than white
adipocytes; their smaller lipid droplets allow the nucleus
to be more centrally located.
- Often closely packed around large capillaries and the
tissue is subdivided by connective tissue partitions into
lobules that are better delineated than the lobules of
white adipose tissue.
- Cells of this tissue receive direct sympathetic innervation,
which regulates their metabolic activity.

Function of Brown Adipocytes

The main function of these multilocular cells is to produce heat

by nonshivering thermogenesis. The physiology of brown fat is best
understood from studies of the tissue of hibernating species.

 In animals ending their hibernation period, and in newborn

humans, nerve impulses liberate norepinephrine into
brown adipose tissue. As in white fat, this
neurotransmitter activates the hormone-sensitive lipase of
adipoctyes, promoting hydrolysis of triglycerides to fatty
acids and glycerol. However, unlike the process in white
fat, liberated fatty acids of multilocular adipocytes are
not released but are quickly metabolized, with a
consequence increase in O2 consumption and heat
production. This raises the temperature within the tissue
and warms the locally circulating blood, which then
distributes the heat throughout the body.

Heat production in brown adipocytes is greater than that of

other cells because their inner mitochondrial membranes have
greatly upregulated levels of the transmembrane protein uncoupling
protein-1 (UCP1) or thermogenin. In the presence of free fatty
acids, UCP1 permits the flow of protons from the intermembranous
space to the matrix without passing through ATP synthetase
complexes. Instead of producing ATP, the energy associated with
this proton flow dissipates as heat.

Histogenesis of brown tissue