Chapter 9: Adipose Tissue
endocrine organ
Adipocytes also regulate energy metabolism by secreting paracrine and endocrine substances. The newly discovered secretory functions of adipocytes have shifted views on adipose tissue, which is now considered a major ____________ _______.
thermogenic needs
Adipocytes are able to undergo white-to-brown and brown-to-white transformation in response to the ______________ __________ of an organism.
small lipid inclusions external lamina
Early lipoblasts look like fibroblasts but develop small ______ __________ and a thin _________ _________.
single large lipid droplet late lipoblasts unilocular
In the late stage of differentiation, the cells increase in size and become more spherical. Small lipid droplets coalesce to form a _______ ________ ________ ___________ that occupies the central portion of the cytoplasm. Smooth-surfaced endoplasmic reticulum (sER) is abundant, whereas rER is less prominent. These cells are designated _____ _____________. Eventually, the lipid mass compresses the nucleus to an eccentric position, producing a signet-ring appearance in hematoxylin and eosin (H&E) preparations. Because these cells have a single lipid droplet, they are designated ____________ adipocytes or mature adipocytes.
thermogenesis
Metabolism of lipid in brown adipose tissue generates heat in process known as ________________.
"master switch" regulator
Most of the PPAR target genes in adipose tissue influence lipogenic pathways and initiate the storage of triglycerides. Therefore, PPAR/RXR is regarded as the _________ _________ _____________ in the white adipocytes' differentiation.
uptake of fatty acids conversion to triglyceride
One of the major metabolic functions of adipose tissue involves the _________ ____ _______ _______ from the blood and their _____________ ___ ___________ within the adipocyte.
ghrelin peptide YY (PYY)
Recently, two small peptide hormones produced in the gastrointestinal tract—___________, an appetite stimulant, and ___________ ___, an appetite suppressant—have been linked to this short-term weight regulation system.
subcutaneous fascia
Since the thermal conductivity of adipose tissue is only about half that of skeletal muscle, the ______________ ________ provides a significant thermal insulation against cold by reducing the rate of heat loss
vimentin filaments
TEM 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 ____________ ____________ measuring 5 to 10 nm in diameter. This layer separates the hydrophobic contents of the lipid droplet from the hydrophilic cytoplasmic matrix.
leptin (ob) gene energy homeostasis
The discovery of the leptin (ob) gene, which encodes a fat-specific messenger RNA (mRNA) for leptin, has given some insight into the mechanism of energy homeostasis
lipid inclusion cytoplasm
The mature adipocyte is characterized by a single, large ________ ___________ surrounded by a thin rim of _____________.
norepinephrine UCP-1
The metabolic activity of brown adipose tissue is largely regulated by ________________ released from the sympa- thetic nerve terminals, which stimulates lipolysis and hy- drolysis of triglycerides as well as increases mitochondrial expression and activity of ________ molecules.
sympathetic nerve system
The metabolic activity of brown adipose tissue is regulated by the _____________ ______ _________ and is related to ambient outdoor temperature.
thermogenesis
The movement of protons from the inner mitochondrial compartment dissipates the mitochondrial proton gradient, thus uncoupling respiration from ATP synthesis. The energy pro- duced by the mitochondria is then dissipated as heat in a process known as?
external lamina
The presence of an __________ _________ is a feature that further distinguishes adipocytes from proper connec- tive tissue cells
Adipose tissue
Tissues in which adipocytes are the primary cell type are designated as?
leptin and insulin
Two major hormones influence this long-term weight regulation system, _______ and _________, along with other hormones, including thyroid hormone, glucocorticoids, and hormones of the pituitary gland
white (unilocular) and brown (multilocular)
What are the two types of adipose tissue?
leptin
What is the most notable member of adipokines? a 16 kDa peptide hormone involved in the regulation of energy homeostasis and is exclusively secreted by adipocytes
White adipose tissue
What is the predominant type of adipose tissue in adult humans?
spherical
When isolated, white adipocytes are ___________, 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.
PR domain containing 16 (PRDM16) PPAR coactivator-1 (PGC-1) "master switch" uncoupling protein thermogenin
When the zinc-finger protein known as ____ ________ _____________ ____ is activated, myogenic progenitor cells synthesize several members of the _______ ______________ family of transcription factors, activating brown adipocyte differen- tiation and suppressing skeletal muscle development. Therefore, PRDM16/PGC-1 is regarded as a ________ __________ regulator in brown adipocytes' differentiation. These factors in turn regulate expression of genes (i.e., UPC-1) that encode a specific mitochondrial protein called _______________ __________ or ______________ (a 33 kDa inner mito- chondrial membrane protein), which is essential for brown adipocyte metabolism (thermogenesis).
fetal development
White adipose tissue begins to form midway through _________ ____________.
subcutaneous (superficial) fascia
White adipose tissue forms a fatty layer of the _____________ __________ called the PANNICULUS ADIPOSUS [Lat. panniculus, a little garment; adipatus, fatty] in the connective tissue beneath the skin
hormones, growth factors, and cytokines
White adipose tissue secretes a variety of adipokines, which include what?
cold exposure and physical activity
White-to-brown transdifferentiation of adipose tissue is induced by what two things?
small lipid droplets midstage lipoblasts
With continued development, the early lipoblasts assume an oval configuration. The most characteristic feature at this stage is an extensive concentration of vesicles and _______ _________ __________ 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 _____________ _____________.
Neural mobilization
__________ _______________ is particularly important during periods of fasting and exposure to severe cold.
White (unilocular)
__________ adipose tissue represents at least 10% of the body weight of a normal healthy individual
Insulin
___________, the pancreatic hormone that REGULATES BLOOD GLUCOSE LEVELS, is also involved in regulation of adipose tissue metabolism. It enhances the conversion of glucose into the triglycerides of the lipid droplet by the adipocyte.
fat droplets
Adipocytes of brown, multilocular adipose tissue contain numerous ______ ___________.
norepinephrine lipase
Adipose cells in the intact contralateral fat pad mobilize fat. It is now known that ________________ (which is liberated by the endings of nerve cells of the sympathetic nervous system) initiates a series of metabolic steps that lead to the activation of _________. This enzyme splits triglycerides, which constitute more than 90% of the lipids stored in the adipocyte. This enzymatic activity is an early step in the mobilization of lipids.
energy homeostasis
Adipose tissue is a specialized CONNECTIVE TISSUE that plays an important role in ___________ ________________?
lipid inclusions external lamina
As lipoblastic differentiation begins, vesicles increase in number, with a corresponding decrease in rough-surfaced endoplasmic reticulum (rER). Small ________ ____________ appear at one pole of the cytoplasm. Pinocytotic vesicles and an __________ __________ also appear.
mesenchymal stem cells skeletal myogenic progenitor
Brown adipocytes are also derived from _______________ _______ ________ but from a different cellular lineage than those differentiating into white adipocytes. Lineage tracing experiments show that brown adipocyte tissue and skeletal muscle derive from common __________ ____________ _____________cells found in dermatomyotomes of developing embryo.
PRDM16/PGC-1
Brown adipocytes differentiate from mesenchymal stem cells under the control of ______________ transcription factors.
bone marrow
Internally, adipose tissue is preferentially located in the greater omentum, mesentery, and retroperitoneal space and is usually abundant around the kidneys. It is also found in ________ _________ and between other tissues, where it fills in spaces. In the palms of the hands and the soles of the feet, beneath the visceral pericardium (around the outside of the heart), and in the orbits around the eyeballs, adipose tissue functions as a cushion.
brain-gut-adipose axis
It is almost impossible to separate regulation of adipose tissue from digestive processes and functions of the central nervous system. These interconnected hormonal and neural signals emanating from the adipose tissue, alimentary tract, and central nervous system form the ______________________ ______ that regulates appetite, hunger, satiety, and energy homeostasis
primitive fat organs
LIPOBLASTS initially develop from stromal-vascular cells along the small blood vessels in the fetus and are free of lipids. These cells are committed to becoming adipocytes at this early stage by expressing PPAR/RXR transcription factors. Collections of such cells are sometimes called __________ ____ ________.
hypothalamus
Leptin also participates in an endocrine signaling pathway that communicates the energy state of adipose tissue to brain centers that regulate food uptake. It acts on the central nervous system by binding to specific receptors, mainly in the ______________. also communicates the fuel state of adipocytes from fat-storage sites to other metabolically active tissues
steroid hormones
Leptin also produces _________ ___________ (testosterone, estrogens, and glucocorticoids).
circulating satiety factor
Leptin inhibits food intake and stimulates metabolic rate and loss of body weight. Thus, leptin fulfills the criteria for a ______________ _______ ________ that controls food intake when the body's store of energy is sufficient
regulates weight
Like leptin, insulin ___________ __________ by acting on brain centers in the hypothalamus.
lipid mass
The _______ ________ in the adipocyte is not membrane-bounded.
short-term weight regulation
The amount of adipose tissue in an individual is regulated by two physiologic systems. The first system, which is associated with _____________ ________ _____________, controls appetite and metabolism on a daily basis.
one associated with short- term weight regulation, the other with long-term weight regulation.
The amount of an individual's adipose tissue is determined by what two physiologic systems?
lipid droplets
The body has a limited capacity to store carbohydrate and protein; therefore, energy reserves are stored within ________ ___________ of adipocytes in the form of TRIGLYCERIDES.
Brown
____________ adipose tissue is present in large amounts in humans during fetal life. It diminishes during the first decade after birth but continues to be present in varied amounts, mainly around internal organs
Hormonal mobilization insulin, thyroid hor- mones, and adrenal steroids
_____________ ______________ involves a complex system of hormones and enzymes that controls fatty-acid release from adipocytes. These include:
Unilocular
_____________ adipocytes are large cells, sometimes 100 m or more in diameter.
Glucagon growth hormone
_____________, another pancreatic hormone, and __________ ____________from the pituitary gland both increase lipid utilization (lipolysis)
loose
Individual fat cells, or adipocytes, and groups of adipocytes are found throughout what kind of connective tissue?
Adipocytes
____________ actively synthesize and secrete adipokines, a group of biologically active substances, which include hormones, growth factors, and cytokines
breast
In both sexes, the mammary fat pad is a preferential site for accumulation of adipose tissue; the nonlactating female ________ is composed primarily of this tissue.
mammary fat pad
In the lactating female, _____________ _____ ______ plays an important role in supporting breast function.
mesenchymal stem cells peroxisome proliferator-activated receptor gamma (PPAR) retinoid X receptor (RXR)
During embryonic development, white adipocytes derive from undifferentiated perivascular _______________ _____ _______ associated with the adventitia of small venules. Current evidence suggests that a transcription factor called peroxisome _____________ __________________ _____________ ________ in complex with the ____________ __ __________ play a critical role in adipocyte differentiation and initia- tion of lipid metabolism. It induces the maturation of early LIPOBLASTS (adipoblasts) or PREADIPOCYTES into mature fat cells of white adipose tissue.
transdifferentiation
Exposure to chronic cold temperatures increases the thermogenic needs of an organism. Studies have shown that in such a condition, mature white adipocytes can transform into brown adipocytes to generate body heat. Conversely, brown adipocytes are able to transform into white adipocytes when the energy balance is positive and the body requires an increase of triglyceride storage capacity. This phenomenon, known as ____________________, was observed in experimental animals.
energy storage insulation cushioning of vital organs secretion of hormones
Functions of white adipose tissue include _________ storage, ___________, cushioning of _______ __________, and secretion of _____________.
brown adipose tissue nonshivering thermogenesis
Hibernating animals have large amounts of ________ __________ _________. The tissue serves as a ready source of lipid. When oxidized, it produces heat to warm the blood flowing through the brown fat on arousal from hibernation and in the maintenance of body temperature in the cold. This type of heat production is known as _________________ __________________.
1. adiponectin, 2. resistin, 3. retinol binding protein 4 (RBP4), 4. visfatin, 5. apelin, 6. plasminogen activator inhibitor-1 (PAI-1), 7. tumor necrosis factors (TNFs), 8. interleukin-6 (IL-6), 9. monocyte chemotactic protein-1 (MCP-1), and 10. angiotensinogen (AGE)
In addition to leptin, adipose tissue secretes a variety of adipokines such as:
tumor necrosis factor α (TNF-α)
In addition, elevated levels of _________ __________ _________ have been implicated as a causative factor in the development of insulin resistance associated with obesity and diabetes.
smaller
The cells of brown (multilocular) adipose tissue are __________ than those of white adipose tissue. The cytoplasm of each cell contains many small lipid droplets, hence the name multilocular, as opposed to white unilocular adipocytes, which contain only one huge lipid droplet.
ghrelin hypothalamus
The potent appetite stimulant ___________ is a small, 28-amino-acid polypeptide produced by gastric epithelial cells. In addition to its appetite stimulatory role, it acts on the anterior lobe of the pituitary gland to release growth hormone. In humans, ghrelin functions through receptors located in the ________________, increasing the sense of hunger.
long-term weight regulation
The second system, which is associated with _____________ _________ _______________, controls appetite and metabolism on a continual basis (over months and years)
peptide YY
The small, 36-amino-acid long gastrointestinal hormone ____________ ___ is produced by the small intestine and plays an important role in promoting and maintaining weight loss by inducing a greater sense of fullness soon after a meal.
mitochondria uncoupling protein (UCP-1)
The unique large, round _______________ in the cyto- plasm of brown adipose tissue cells contain ______________ _________, which uncouples the oxidation of fatty acids from the production of ATP. Therefore, protons are allowed to travel from the intermembrane space back to the mitochondrial matrix along the gradient without passing through ATP synthase and thus without producing ATP.
UCP-1
Thermogenic activity of brown adipose tissue is facili- tated by __________ that is found at the inner mitochondrial membrane.
mobilization albumin
When adipose tissue is stimulated by neural or hormonal mechanisms, triglycerides are broken down into glycerol and fatty acids, a process called? The fatty acids pass through the adipocyte cell membrane to enter a capillary. Here they are bound to the carrier protein ___________ and transported to other cells, which use fatty acids as metabolic fuel.