Encyclopedia of human nutrition

2291 Pages·1999·63.605 MB·English

by  M J Sadler, J J Strain, Benjamin Caballero

A
Acids see Electrolytes:Acid-Base Balance
ADIPOSE TISSUE
GFru¨hbeckandJGo´mez-Ambrosi,Universidadde varying greatly among species. Adipocytes differ-
Navarra, Pamplona, Spain entiate from stellate or fusiform precursor cells of
mesenchymal origin. There are two processes of
ª2005ElsevierLtd.Allrightsreserved.
adipose tissue formation. In the primary fat for-
mation, which takes place relatively early (in
human fetuses the first traces of a fat organ are
Introduction
detectable between the 14th and 16thweeks of
The role of white adipose tissue (WAT) in storing prenatal life), gland-like aggregations of epithe-
and releasing lipids for oxidation by skeletal muscle loid precursor cells, called lipoblasts or
and other tissues became so firmly established preadipocytes, are laid down in specific locations
decadesagothatapersistentlackofinteresthindered and accumulate multiple lipid droplets becoming
the study of the extraordinarily dynamic behavior brown adipocytes. The secondary fat formation
of adipocytes. However, disentangling the neuro- takes place later in fetal life (after the 23rdweek
endocrine systems that regulate energy homeostasis of gestation) as well as in the early postnatal
and adiposity has jumped to a first-priority chal- period, whereby the differentiation of other
lenge, with the recognition of obesity as one of the fusiform precursor cells that accumulate lipid to
major public health problems. Strictly speaking, ultimately coalesce into a single large drop per
obesity is not defined as an excess of body weight cell leads to the dissemination of fat depots
but as an increased adipose tissue accretion, to the formed by unilocular white adipocytes in many
extent that health may be adversely affected. There- areas of connective tissue. Adipose tissue may be
fore, in the last decades, adipose tissue has become partitioned by connective tissue septa into
the research focus of biomedical scientists for epide- lobules. The number of fat lobules remains con-
miological, pathophysiological, and molecular stant, while in the subsequent developmental
reasons. Although the primary role of adipocytes is phases the lobules continuously increase in size.
to store triglycerides during periods of caloric excess At the sites of early fat development, a multilo-
and to mobilize this reserve when expenditure cular morphology of adipocytes predominates,
exceeds intake, it is now widely recognized that reflecting the early developmental stage. Micro-
adipose tissue liesatthe heartofacomplex network scopic studies have shown that the second trime-
that participates in the regulation of a variety of ster may be a critical period for the development
quite diverse biological functions (Figure 1). of obesity in later life. At the beginning of the
third trimester, adipocytes are present in the main
fat depots but are still relatively small. During
embryonic development it is important to empha-
Development
size the temporospacial tight coordination of
Adipose tissue develops extensively in home- angiogenesis with the formation of fat cell
otherms with the proportion to body weight clusters. At birth, body fat has been reported to
2 ADIPOSE TISSUE
adipose cells. In this case, adipocytes may be four
Appetite
regulation times their normal size. If the positive energy bal-
ance is maintained, a hyperplasic or hypercellular
Body weight Vascular tone obesity characterized by a greater than normal
homeostasis control
number of cells is developed. Recent observations
regarding the occurrence of apoptosis in WAT have
changed the traditional belief that acquisition of fat
Immunity Fibrinolysis
cells is irreversible. The adipose lineage originates
WAT
from multipotent mesenchymal stem cells that
develop into adipoblasts (Figure 2). Commitment
Reproduction Coagulation of these adipoblasts gives rise to preadipose cells
(preadipocytes), which are cells that have expressed
early but not late markers and have yet to accumu-
Others Angiogenesis
late triacylglycerol stores (Figure 3). Multipotent
Glucose and lipid
stem cells and adipoblasts, which are found during
metabolism
embryonic development, are still present postnatally.
Figure 1 Dynamicview of whiteadipose tissue basedon the
pleiotropiceffectsonquitediversephysiologicalfunctions. The relationship between brown and white fat dur-
ing development has not been completely solved.
Brown adipocytes can be detected among all white
account for approximately 16% of total body fat depots in variable amounts depending on species,
weight (with brown fat constituting 2–5%) with localization, and environmental temperature. The
an increase in body fat of around 0.7–2.8kg dur- transformation of characteristic brown adipocytes
ing the first year of life. into white fat cells can take place rapidly in numer-
Adipogenesis, i.e., the development of adipose ous species and depots during postnatal
tissue, varies according to sex and age. Further- development.
more, the existence of sensitive periods for changes The morphological and functional changes that
in adipose tissue cellularity throughout life has been take place in the course of adipogenesis represent a
postulated. In this regard, two peaks of accelerated shift in transcription factor expression and activity
adipose mass enlargement have been established, leading from a primitive, multipotent state to a final
namely after birth and between 9 and 13years of phenotype characterized by alterations in cell shape
age. The capacity for cell proliferation and differ- andlipidaccumulation.Variousredundantsignaling
entiation is highest during the first year of life, pathwaysandtranscriptionfactorsdirectlyinfluence
while it is less pronounced in the years before fat cell development by converging in the upregula-
puberty. Thereafter, the rate of cell proliferation tion of PPAR(cid:1), which embodies a common and
slows down during adolescence and, in weight essential regulator of adipogenesis as well as of adi-
stable individuals, remains fairly constant through- pocyte hypertrophy. Among the broad panoply of
out adulthood. In case of a maintained positive transcription factors, C/EBPs and the basic helix-
energy balance adipose mass expansion takes places loop-helix family (ADD1/SREBP-1c) also stand out
initially by an enlargement of the existing fat cells. together with their link with the existing nutritional
The perpetuation of this situation ends up in severe status. The transcriptional repression of adipogen-
obesity where the total fat cell number can be easily esis includes both active and passive mechanisms.
trebled. Childhood-onset obesity is characterized by The former directly interferes with the transcrip-
a combination of fat cell hyperplasia and hypertro- tional machinery, while the latter is based on the
phy, whereas in adult-onset obesity a hypertrophic bindingofnegativeregulatorstoyieldinactiveforms
growth predominates. However, it has been of known activators.
recently shown that adult humans are capable of Hormones, cytokines, growth factors, and nutri-
new adipocyte formation, with fat tissue containing ents influence the dynamic changes related to adi-
a significant proportion of cells with the ability pose tissue mass as well as its pattern of distribution
to undergo differentiation. Interestingly, the hyper- (Figure 4). The responsiveness of fat cells to neuro-
plasic growth of fat cells in adults does not take humoral signals may vary according to peculiarities
place until the existing adipocytes reach a critical in the adipose lineage stage at the moment of expo-
cell size. sure. Moreover, the simultaneous presence of some
Initially, excess energy storage starts as hyper- adipogenic factors at specific threshold concentra-
trophic obesity resulting from the accumulation of tions may be a necessary requirement to trigger
excess lipid in a normal number of unilocular terminal differentiation.
ADIPOSE TISSUE 3
Figure2 Schematicdiagramofthehistogenesisofwhiteandbrownadipocytes.C/EBPs,CCAAT/enhancerbindingproteins;PGC-1(cid:2),
peroxisomeproliferator-activatedreceptor-(cid:1) coactivator-1;PPAR(cid:1),peroxisomeproliferator-activatedreceptor-(cid:1).
Structure
these account for the remaining 75% of the total
Adipose tissue is a special loose connective tissue cell population, representing a wide range of targets
dominated by adipocytes. The name of these cells for extensive autocrine-paracrine cross-talk.
is based on the presence of a large lipid droplet with Adipocytes, which are typically spherical and
‘adipo’ derived from the Latin adeps meaning ‘per- vary enormously in size (20–200mm in diameter,
taining tofat.’Inadiposetissue,fatcellsareindivid- with variable volumes ranging from a few picoliters
ually held in place by delicate reticular fibers to about 3 nanoliters), are embedded in a connec-
clustering in lobular masses bounded by fibrous tive tissue matrix and are uniquely adapted to store
septa surrounded by a rich capillary network. In and release energy. Surplus energy is assimilated by
adults, adipocytes may comprise around 90% of adipocytes and stored as lipid droplets. The stored
adipose mass accounting only for roughly 25% of fat is composed mainly of triacylglycerols (about
the total cell population. Thus, adipose tissue itself 95% of the total lipid content comprised princi-
is composed not only of adipocytes, but also other pally of oleic and palmitic acids) and to a smaller
cell types called the stroma-vascular fraction, com- degree of diacylglycerols, phospholipids, unesteri-
prising blood cells, endothelial cells, pericytes, and fied fatty acids, and cholesterol. To accommodate
adipose precursor cells among others (Figure 5); the lipids adipocytes are capable of changing their
4 ADIPOSE TISSUE
Mesenchymal Immature Mature
stem cell Adipoblast Preadipocyte adipocyte adipocyte
Clonal Lipid
Molecular/ Proliferation expansion accumulation
physiological
Growth arrest +
events
early markers’ appearance
and
emerging
regulatory genes
Pref-1
ECM alterations
Cytoskeletal remodeling
LPL
CD36
SREBP-1
C/EBPβ & δ
PPARγ
C/EBPα
GLUT4
Lipogenic enzymes
aP2
Leptin & other secreted factors
Figure 3 Multistep process of adipogenesis together with events and participating regulatory elements. aP2, adipocyte fatty acid
bindingprotein;C/EBP(cid:2),CCAAT/enhancerbindingprotein(cid:2);C/EBP(cid:3) &(cid:4),CCAAT/enhancerbindingprotein(cid:3) &(cid:4);CD36,fattyacid
translocase; ECM,extracellular matrix;GLUT4,glucosetransportertype 4;LPL,lipoproteinlipase; PPAR(cid:1), peroxisomeproliferator-
activatedreceptor-(cid:1);Pref-1,preadipocytefactor-1;SREBP-1,sterolregulatoryelementbindingprotein-1.
diameter 20-fold and their volumes by several thou- formation of new adipocytes from the precursor
sand-fold. However, fat cells do not increase in size pool takes place.
indefinitely. Once a maximum capacity is attained, Histologically, the interior of adipocytes appears
which in humans averages 1000picoliters, the unstained since the techniques of standard tissue
ADIPOGENIC ANTIADIPOGENIC
FACTORS FACTORS
• angiotensin II • catecholamines
• diet rich in saturated fat • EGF
• estrogens • flavonoids
• glucocorticoids • GH
• IGF-1 • IL-1
• insulin • IL-6
• LIF • leptin
• long-chain fatty acids • PDGF
• lysophosphatidic acid • PGF2α
• MCSF • testosterone
• PAI-1 • TGF-β
• PPARs • TNF-α
• prolactin
• retinoids
• thyroid hormones
Figure4 Factorsexertingadirecteffectonadiposemass.EGF,epidermalgrowthfactor;GH,growthhormone;IGF-1,insulin-like
growth factor-1; IL-1, interleukin-1; IL-6, interleukin-6; LIF, leukemia inhibitory factor; MCSF, macrophage colony stimulating factor;
PAI-1, plasminogen activator inhibitor-1; PDGF, platelet-derived growth factor; PGF , prostaglandin F ; PPARs, peroxisome
2(cid:2) 2(cid:2)
proliferator-activatedreceptors;TGF-(cid:3),transforminggrowthfactor-(cid:3);TNF-(cid:2),tumornecrosisfactor-(cid:2).
ADIPOSE TISSUE 5
35–70%
adipocytes
Stromal cell fraction
(cid:127) fibroblasts (cid:127) preadipocytes
(cid:127) blood cells (cid:127) poorly differentiated
(cid:127) endothelial cells mesenchymal cells
(cid:127) pericytes (cid:127) very small fat cells WAT
Figure5 Schematicrepresentationofcelltypespresentinadiposetissue.WAT,whiteadiposetissue.
preparation dissolve out the lipids, leaving a thin granular endoplasmic reticulum. Occasional lyso-
rim of eosinophilic cytoplasm that typically loses its somes can be found. The coalescent lipid droplets
round shape during tissue processing, thus contrib- contain a mixture of neutral fats, triglycerides, fatty
uting to the sponge-like appearance of WAT in acids, phospholipids, and cholesterol. A thin inter-
routine preparations for light microscopy (Figure 6 face membrane separates the lipid droplet from the
and Figure 7). Owing to the fact that about 90% of cytoplasmic matrix. Peripheral to this membrane is
the cell volume is a lipid droplet, the small dark a system of parallel meridional thin filaments.
nucleus becomes a flattened semilunar structure Because of the size of these cells, relative to the
pushed against the edge of the cell and the thin thickness of the section, the nucleus (accounting
cytoplasmic rim is also pushed to the periphery of for only one-fortieth of the cell volume) may not
the adipocytes. Mature white adipose cells contain always be present in the section. Unilocular adipo-
a single large lipid droplet and are described as cytes usually appear in clumps near blood vessels,
unilocular. However, developing white adipocytes which is reasonable since the source and dispersion
are transiently multilocular containing multiple of material stored in fat cells depends on transpor-
lipid droplets before these finally coalesce into a tation by the vascular system.
single large drop (Figure 8). The nucleus is round Brown fat is a specialized type of adipose tissue
or oval in young fat cells, but is cup-shaped and that plays an important role in body temperature
peripherally displaced in mature adipocytes. The regulation. In the newborn brown fat is well
cytoplasm is stretched to form a thin sheath around developed in the neck and interscapular region.
the fat globule, although a relatively large volume is It has a limited distribution in childhood, and
concentrated around the nucleus. A thin external occurs only to a small degree in adult humans,
lamina called basal lamina surrounds the cell. The while it is present in significant amounts in
smooth cell membrane shows no microvilli but has rodents and hibernating animals. The brown
abundant smooth micropinocytotic invaginations color is derived from a rich vascular network
that often fuse to form small vacuoles appearing and abundant mitochondria and lysosomes. The
as rosette-like configurations (Figure 9). Mitochon- individual multilocular adipocytes are frothy
dria are few in number with loosely arranged mem- appearing cells due to the fact that the lipid,
branous cristae. The Golgi zone is small and the which does not coalesce as readily as in white
cytoplasm is filled with free ribosomes, but contains fat cells and is normally stored in multiple small
only a limited number of short profiles of the droplets, has been leached out during tissue
6 ADIPOSE TISSUE
(A)
(A)
(B)
Figure 6 (A) Human subcutaneous white adipose tissue (B)
withMassontrichromestaining(10(cid:1); bar=100mm).(B)Same
Figure7 (A)HumanomentalwhiteadiposetissuewithMasson
tissue at a higher magnification (40(cid:1); bar=25mm). (Courtesy
trichrome staining (10(cid:1); bar=100mm). (B) Same tissue at a
of Dr. M A Burrell and M Archanco, University of Navarra,
higher magnification (40(cid:1); bar=25mm). (Courtesy of Dr. M A
Spain.)
BurrellandMArchanco,UniversityofNavarra,Spain.)
processing (Figure 10). The spherical nuclei are
Distribution
centrally or eccentrically located within the cell.
Compared to the unilocular white adipocytes, the White adipose tissue mayrepresent the largest endo-
cytoplasm of the multilocular brown fat cell is crine tissue of the whole organism, especially in
relatively abundant and strongly stained because overweight and obese patients. The anatomical dis-
of the numerous mitochondria present. The mito- tributionofindividualfatpadsdispersedthroughout
chondria are involved in the oxidation of the the whole body and not connected to each other
stored lipid, but because they exhibit a reduced contradicts the classic organ-specific localization.
potential to carry out oxidative phosphorylation, WAT exhibits clear, regional differences in its sites
the energy produced is released in the form of of predilection (Table 1). The hypodermal region
heat due to the uncoupling activity of UCP and invariably contains fat, except in a few places such
not captured in adenosine triphosphate (ATP). as the eyelids and the scrotum. Adipocytes also
Therefore, brown adipose tissue is extremely accumulatearoundorganslikethekidneysandadre-
well vascularized so that the blood is warmed nals, in the coronary sulcus of the heart, in bone
when it passes through the active tissue. marrow, mesentery, and omentum. Unilocular fat is
ADIPOSE TISSUE 7
Figure8 Paraffinsectionofratabdominalwhiteadiposetissue
with a hematoxylin and eosin stain showing the simultaneous
presenceofuni-andmultilocularadipocytes(40(cid:1);bar=25mm).
(Courtesy of Dr. M A Burrell and M Archanco, University of
Navarra,Spain.)
widely distributed in the subcutaneous tissue of (A)
humans but exhibits quantitative regional differ-
ences that are influenced by age and sex. In infants
and young children there is a continuous subcuta-
neous fat layer, the panniculus adiposus, over the
whole body. This layer thins out in some areas in
adultsbutpersistsandgrowsthickerincertainother
regions. The sites differ in their distribution among
sexes, being responsible for the characteristic body
form of males and females, termed android and
ginecoid fat distribution. In males, the main regions
include the nape of the neck, the subcutaneous
area over the deltoid and triceps muscles, and the
lumbosacral region. In females, subcutaneous fat is
most abundant in the buttocks, epitrochanteric
region, anterior and lateral aspects of the thighs, as
well as the breasts. Additionally, extensive fat
depots are found in the omentum, mesenteries, and
the retroperitoneal area of both sexes. In well-
nourished, sedentary individuals, the fat distribution
persists and becomes more obvious with advancing
age with males tending to deposit more fat in the
visceral compartment. Depot-specific differences
may be related not only to the metabolism of fat
cells but also to their capacity to form new adipo-
(B)
cytes. Additionally, regional differences may result
Figure 9 (A) Transmission electron micrographs with the
from variations in hormone receptor distribution as
characteristicallydisplacednucleustoonesideandslightlyflattened
well as from specific local environmental character- bytheaccumulatedlipid.Thecytoplasmofthefatcellisreducedto
istics as a consequence of differences in innervation a thin rim around the lipid droplet (7725(cid:1)). (B) The cytoplasm
and vascularization. containsseveralsmalllipiddropletsthathavenotyetcoalesced.A
fewfilamentousmitochondria,occasionalcisternaeofendoplasmic
Regional distribution of body fat is known to
reticulum,and amoderate number of free ribosomesare usually
be an important indicator for metabolic and
visible(15000(cid:1)). (Courtesy of Dr.M A Burrell and M Archanco,
cardiovascular alterations in some individuals. UniversityofNavarra,Spain.)
8 ADIPOSE TISSUE
Table1 Distributionofmainhumanadiposetissuedepots
Subcutaneous(approx.80%;deepþsuperficiallayers)
Truncal
–Cervical
–Dorsal
–Lumbar
Abdominal
Gluteofemoral
Mammary
Visceral(approx.20%;thoracic-abdominal-pelvic)
Intrathoracic(extra-intrapericardial)
Intra-abdominopelvic
–Intraperitoneal
Omental(greaterandlesseromentum)
Mesenteric(epiplon,smallintestine,colon,rectum)
Umbilical
–Extraperitoneal
Peripancreatic(infiltratedwithbrownadipocytes)
Perirenal(infiltratedwithbrownadipocytes)
(A)
–Intrapelvic
Gonadal(parametrial,retrouterine,retropubic)
Urogenital(paravesical,para-retrorectal)
Intraparenchymatous(physiologicallyorpathologically)
Inter-intramuscularandperimuscular(insidethemusclefascia)
Perivascular
Paraosseal(interfacebetweenboneandmuscle)
Ectopic(steatosis,intramyocardial,lypodystrophy,etc.)
Hyperlipidemia
Cardiovascular
Metabolic syndrome
disease
Cancer Infertility
Obstructive Psychosocial
sleep apnea AAddiippoossiittyy distress
(B)
Hyperuricemia Osteoarthritis
Figure10 (A)Paraffinsectionofratbrownadiposetissuewith
a hematoxylin and eosin stain (20(cid:1); bar=50mm). (B) Same Atherosclerosis/ Gastrointestinal
tissue at a higher magnification (40(cid:1); bar=25mm). (Courtesy inflammation alterations
ofDr.MABurrellandMArchanco,UniversityofNavarra.) Others
Figure 11 Main comorbidities associated with increased
The observation that the topographic distribution adiposity.
of adipose tissue is relevant to understanding the
relation of obesity to disturbances in glucose and alterations, which lead to the development of a
lipid metabolism was formulated before the 1950s. wide range of comorbidities (Figure 11).
Since then numerous prospective studies have
revealed that android or male-type obesity corre-
Function
lates more often with an elevated mortality and
risk for the development of diabetes mellitus type Although many cell types contain small reserves of
2, dyslipidemia, hypertension, and atherosclerosis carbohydrate and lipid, the adipose tissue is the
than gynoid or female-type obesity. Obesity has body’s most capacious energy reservoir. Because of
been reported to cause or exacerbate a large num- thehighenergycontentperunitweightoffataswell
ber of health problems with a known impact on as its hydrophobicity, the storage of energy in the
both life expectancy and quality of life. In this formoftriglyceridesis ahighlyefficient biochemical
respect, the association of increased adiposity is phenomenon (1g of adipose tissue contains around
accompanied by important pathophysiological 800mg triacylglycerol and only about 100mg of
ADIPOSE TISSUE 9
water). It represents quantitatively the most variable hormone or ‘lipostat’ in a negative feedback control
component of the organism, ranging from a few per from adipose tissue to hypothalamic receptors
centofbodyweightintopathletestomorethanhalf informs the brain about the abundance of body fat,
of the total body weight in severely obese patients. thereby allowing feeding behavior, metabolism, and
The normal range is about 10–20% body fat for endocrine physiology to be coupled to the nutri-
males and around 20–30% for females, accounting tional state of the organism. The existing body of
approximately for a 2-month energy reserve. During evidence gathered in the last decades through tar-
pregnancy most species accrue additional reserves of geted expression or knockout of specific genes
adipose tissue to help support the development of involved in different steps of the pathways control-
the fetus and to further facilitate the lactation ling food intake, body weight, adiposity, or fat
period. distribution has clearly contributed to unraveling
Energy balance regulation is an extremely com- the underlying mechanisms of energy homeostasis.
plex process composed of multiple interacting The findings have fostered the notion of a far more
homeostatic and behavioral pathways aimed at complex system than previously thought, involving
maintainingconstantenergystores.Itisnowevident the integration of a plethora of factors.
that body weight control is achieved through highly Theidentificationofadiposetissueasamultifunc-
orchestrated interactions between nutrient selection, tional organ as opposed to a passive organ for the
organoleptic influences, and neuroendocrine storage of excess energy in the form of fat has been
responses to diet as well as being influenced by brought about by the emerging body of evidence
genetic and environmental factors. The concept gathered during the last few decades. This pleiotro-
that circulating signals generated in proportion to pic nature is based on the ability of fat cells to
body fat stores influence appetite and energy expen- secrete a large number of hormones, growth factors,
diture in a coordinated manner to regulate body enzymes, cytokines, complement factors, and matrix
weight was proposed almost 50years ago. Accord- proteins, collectively termed adipokines or adipocy-
ing to this model, changes in energy balance suffi- tokines (Table 2, Figure 12), at the same time as
cient to alter body fat stores are signaled via one or expressing receptors for most of these factors
more circulating factors acting in the brain to elicit (Table 3), which warrants extensive cross-talk at a
compensatory changes in order to match energy local and systemic level in response to specific exter-
intake to energy expenditure. This was formulated nal stimuli or metabolic changes. The vast majority
as the ‘lipostatic theory’ assuming that as adipose of adipocyte-derived factors have been shown to be
tissue mass enlarges, a factor that acts as a sensing dysregulated in alterations accompanied by changes
Table2 Relevantfactorssecretedbyadiposetissueintothebloodstream
Molecule Function/effect
Adiponectin/ACRP30/AdipoQ/ Playsaprotectiveroleinthepathogenesisoftype2diabetesandcardiovasculardiseases
apM1/GBP28
Adipsin Possiblelinkbetweenthecomplementpathwayandadiposetissuemetabolism
Angiotensinogen PrecursorofangiotensinII;regulatorofbloodpressureandelectrolytehomeostasis
ASP Influencestherateoftriacylglycerolsynthesisinadiposetissue
FFA Oxidizedintissuestoproducelocalenergy.Serveasasubstratefortriglycerideandstructural
moleculessynthesis.Involvedinthedevelopmentofinsulinresistance
Glycerol Structuralcomponentofthemajorclassesofbiologicallipidsandgluconeogenicprecursor
IGF-I Stimulatesproliferationofawidevarietyofcellsandmediatesmanyoftheeffectsofgrowth
hormone
IL-6 Implicatedinhostdefense,glucoseandlipidmetabolism,andregulationofbodyweight
Leptin Signalstothebrainaboutbodyfatstores.Regulationofappetiteandenergyexpenditure.Wide
varietyofphysiologicalfunctions
NO Importantregulatorofvasculartone.Pleiotropicinvolvementinpathophysiologicalconditions
PAI-1 Potentinhibitorofthefibrinolyticsystem
PGI &PGF Implicatedinregulatoryfunctionssuchasinflammationandbloodclotting,ovulation,menstruation,
2 2(cid:2)
andacidsecretion
Resistin Putativeroleininsulinresistance
Mayparticipateininflammation
TNF-(cid:2) Interfereswithinsulinreceptorsignalingandisapossiblecauseofthedevelopmentofinsulin
resistanceinobesity
VEGF Stimulationofangiogenesis
10 ADIPOSE TISSUE
VVaassooaaccttiivvee ffaaccttoorrss IImmmmuunnee rreessppoonnssee
LLiippiidd mmeettaabboolliissmm
Angiotensinogen Adipsin
ApoE
Monobutyrin ASP
LPL
Adiponectin Factors B and C3
Glycerol
PAI-1 CSFs
Eicosanoids IL-17 D
VEGF SAA3
Tissue factor
Nitric oxide GGrroowwtthh ffaaccttoorrss
TGFβ
Binding proteins IGF-1
HGF
Retinol NGF
Lysophosphatidic acid
PGI2, PGF2α
IInnffllaammmmaattiioonn LIF
Fibronectin
IL-1Ra
IL-1β GGlluuccoossee mmeettaabboolliissmm
IL-8 Others
IL-10 FFA
Cytokines
CRP Resistin
Mα1C-aPc-i1d glycoprot. TNFα + sR PPrrootteeiinnss eexxttrraacceelllluullaarr mmaattrriixx
IL-6 + sR
VAP-1/SSAO
Leptin Osteonectin
Figure12 Factorssecretedbywhiteadiposetissue,whichunderliethemultifunctionalnatureofthisendocrineorgan.Althoughdue
totheirpleiotropiceffectssomeoftheelementsmightbeincludedinmorethanonephysiologicalrole,theyhavebeenincludedonly
underonefunctionforsimplicityreasons.apoE,apolipoproteinE;ASP,acylation-stimulatingprotein;CRP,C-reactiveprotein;CSFs,
colony-stimulatingfactors;FFA,freefattyacids;HGF,hepatocytegrowthfactor;IGF-1,insulin-likegrowthfactor-1;IL-10,interleukin-10;
IL-17 D, interleukin-17 D; IL-1Ra, interleukin-1 receptor antagonist; IL-1(cid:3), interleukin-1(cid:3); IL-6, interleukin, 6; IL-8, interleukin-8; LIF,
leukemia inhibitory factor; LPL, lipoprotein lipase; MCP-1, monocyte chemoattractant protein-1; NGF, nerve growth factor; PAI-1,
plasminogen activator inhibitor -1; PGF , prostaglandin F ; PGI , prostacyclin; SAA3, serum amyloid A3; sR, soluble receptor;
2(cid:2) 2(cid:2) 2
TGF-(cid:3), transforming growth factor-(cid:3); TNF-(cid:2), tumor necrosis factor-(cid:2); VAP-1/SSAO, vascular adhesion protein-1/semicarbazide-
sensitiveamineoxidase;VEGF,vascularendothelialgrowthfactor.
in adipose tissue mass such as overfeeding and carry out an extensive cross-talk at both a local and
lipodystrophy, thus providing evidence for their systemic level in response to specific external stimuli
implication in the etiopathology and comorbidities or neuroendocrine changes. This secretory nature
asssociated with obesity and cachexia. has prompted the view of WAT as an extremely
WAT is actively involved in cell function regula- active endocrine tissue. Interestingly, the high num-
tion through a complex network of endocrine, para- ber and ample spectrum of genes found to be
crine, and autocrine signals that influence the expressed in WAT together with the changes
response of many tissues, including hypothalamus, observed in samples of obese patients substantiates
pancreas, liver, skeletal muscle, kidneys, endothe- the view of an extraordinarily active and plastic
lium, and immune system, among others. Adipose tissue. The complex and complementary nature of
tissue serves the functions of being a store for the expression profile observed in adipose tissue
reserve energy, insulation against heat loss through from obese organisms reflects a plethora of adaptive
the skin, and a protective padding of certain organs. changesaffectingcrucialphysiologicalfunctionsthat
A rapid turnover of stored fat can take place, and may need to be further explored through genomic
with only a few exceptions (orbit, major joints as and proteomic approaches.
wellaspalmandfootsole),theadiposetissuecanbe The endocrine activity of WAT was postulated
usedupalmostcompletelyduringstarvation.Adipo- almost 20years ago when the tissue’s ability for
cytes are uniquely equipped to participate in the steroid hormone interconversion was alluded to. In
regulation of other functions such as reproduction, recent years, especially since the discovery of lep-
immune response, blood pressure control, coagula- tin, the list of adipocyte-derived factors has been
tion, fibrinolysis, and angiogenesis, among others. increasing at a phenomenal pace. Another way of
Thismultifunctionalnatureisbasedontheexistence addressing the production of adipose-derived fac-
of the full complement of enzymes, regulatory pro- tors is by focusing on the function they are impli-
teins, hormones, cytokines, and receptors needed to cated in (Figure 12). One of the best known