Obesity has become a major worldwide health prob-
lem, not least because it is strongly associated with
a number of diseases, including insulin resistance,
type 2 diabetes, atherosclerosis and ischaemic heart
disease, that reduce life expectancy and together have
huge economic and societal consequences. Increasing
evidence indicates that obesity is causally linked to a
chronic low-grade inflammatory state1,2, which con-
tributes to the development of obesity-linked disor-
ders, in particular to metabolic dysfunction. It is now
well established that adipose tissue is not only involved
in energy storage but also functions as an endocrine
organ that secretes various bioactive substances3,4.
The dysregulated expression of these factors, caused
by excess adiposity and adipocyte dysfunction, has
been linked to the pathogenesis of various disease
processes through altered immune responses. As such,
much attention has been paid to developing a better
understanding of the immunoregulatory functions of
adipose tissue. New factors secreted by adipose tissue
have been identified that either promote inflammatory
responses and metabolic dysfunction or contribute to
the resolution of inflammation and have beneficial
effects on obesity-linked metabolic disorders. These
findings lend additional support to the notion that an
imbalance of pro- and anti-inflammatory adipokines
secreted by adipose tissue contributes to metabolic
Obesity and inflammation
Clinical observations. Obesity — in particular, excess
visceral adiposity — is strongly associated with insu-
lin resistance, hypertension and dyslipidaemia, which
contribute to high rates of mortality and morbidity.
Accumulating evidence indicates that a state of chronic
inflammation has a crucial role in the pathogenesis of
obesity-related metabolic dysfunction1,2. Indeed, clini-
cal and epidemiological studies have described a clear
connection between the development of low-grade
inflammatory responses and metabolic diseases, par-
ticularly in the context of obesity and type 2 diabetes.
Excess adipose mass (as occurs in obese individuals)
is associated with increased levels of the pro-inflam-
matory marker C-reactive protein (CRP) in the blood5.
Increased levels of CRP, and its inducer interleukin-6
(IL-6), are predictive of the development of type 2 dia-
betes in various populations5,6. In addition, interven-
tions aimed at causing weight loss lead to reductions
in the levels of pro-inflammatory proteins, including
CRP and IL-6 (Ref. 7).
The adipokine concept. Adipose tissue was traditionally
considered to be a long-term energy storage organ, but it
is now appreciated that it has a key role in the integration
of systemic metabolism. This metabolic function is medi-
ated, in part, by its ability to secrete numerous proteins.
Factors that are secreted by adipose tissue are collectively
*Department of Molecular
University Graduate School of
Medicine, 65 Tsurumai-cho
Institute, Boston University
School of Medicine, 715
Albany Street, W611, Boston,
Massachusetts 02118, USA.
Correspondence to K.W.
21 January 2011
A condition characterized
by the inability of cells (in
the muscle, liver and fat)
to respond appropriately to
endogenous insulin, resulting in
increased blood glucose levels.
Adipokines in inflammation and
Noriyuki Ouchi*, Jennifer L. Parker‡, Jesse J. Lugus‡ and Kenneth Walsh‡
Abstract | The worldwide epidemic of obesity has brought considerable attention to
research aimed at understanding the biology of adipocytes (fat cells) and the events
occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating
evidence indicates that obesity causes chronic low-grade inflammation and that this
contributes to systemic metabolic dysfunction that is associated with obesity-linked
disorders. Adipose tissue functions as a key endocrine organ by releasing multiple
bioactive substances, known as adipose-derived secreted factors or adipokines, that
have pro-inflammatory or anti-inflammatory activities. Dysregulated production or
secretion of these adipokines owing to adipose tissue dysfunction can contribute to
the pathogenesis of obesity-linked complications. In this Review, we focus on the
role of adipokines in inflammatory responses and discuss their potential as regulators
of metabolic function.
NATuRE REvIEws | Immunology
vOLumE 11 | FEbRuARy 2011 | 85
focus on metabolism and immunology
© 2011 Macmillan Publishers Limited. All rights reserved
referred to as adipokines3,4. Importantly, following the onset
of obesity, the secretory status of an adipose tissue depot can
be modified by changes in the cellular composition of the
tissue, including alterations in the number, phenotype and
localization of immune, vascular and structural cells. The
expression of adipokines can also vary depending on the
site of an adipose tissue depot (fIG. 1). The two most abun-
dant depots are visceral and subcutaneous adipose tissues,
which produce unique profiles of adipokines8,9. In addition,
adipocyte depots occur throughout the body in associa-
tion with multiple organs, including the heart and kidneys.
Adipocytes are also found in the bone marrow, lungs and
the adventitia of major blood vessels. In some instances,
it has been shown that high-calorie diets can promote the
development of a pro-inflammatory state in these depots in
a similar manner to that observed in subcutaneous and vis-
ceral adipose tissue (for example, see Ref. 10). Although the
functional importance of many of these individual adipose
depots is generally not known, recent evidence suggests that
diet-induced changes in their adipokine secretion can influ-
ence the function of the associated tissue11. brown adipose
tissue, which is mainly found in infants and hibernating
animals, is functionally distinct from white adipose tissue,
and is not covered in this Review.
Adipsin (also known as complement factor D) was
identified as an adipokine in 1987 (Ref. 12). In 1993,
tumour necrosis factor (TNF) was identified as a pro-
inflammatory product of adipose tissue that is induced
in models of diabetes and obesity, providing evidence for
a functional link between obesity and inflammation13.
subsequently, leptin was identified as an adipose tissue-
specific secreted protein that regulates food intake and
energy expenditure in an endocrine manner14. similarly,
the identification of plasminogen activator inhibitor 1
(PAI1), an inhibitor of fibrinolysis, as an adipokine that is
strongly upregulated in visceral adipose depots in obes-
ity15 suggested a mechanistic link between obesity and
thrombotic disorders. At about the same time, adiponec-
tin (also known as ACRP30 and ADIPOQ) was identi-
fied as an adipocyte-specific adipokine16–18. Adiponectin
expression was found to be decreased in obesity, and stud-
ies in experimental organisms showed that adiponectin
protects against several metabolic and cardiovascular
disorders that are associated with obesity. These results
were surprising as most adipokines stimulate inflamma-
tory responses, are upregulated in obesity and promote
obesity-induced metabolic and cardiovascular diseases.
Collectively, these findings have led to the notion that
metabolic dysfunction that is due to excess adipose tissue
mass may partly result from an imbalance in the expres-
sion of pro- and anti-inflammatory adipokines, thereby
contributing to the development of obesity-linked compli-
cations. Accordingly, the concept that adipokines function
as regulators of body homeostasis has received widespread
attention from the research community (TABLe 1).
Infiltration of immune cells into adipose tissue. Adipose
tissue is mainly comprised of adipocytes, although other
cell types contribute to its growth and function, including
pre-adipocytes, lymphocytes, macrophages, fibroblasts
and vascular cells (fIG. 2a). Obesity can lead to changes
in the cellular composition of the fat pad as well as to the
modulation of individual cell phenotypes (BOX 1). Adipose
tissues in obese individuals and in animal models of obes-
ity are infiltrated by a large number of macrophages, and
this recruitment is linked to systemic inflammation and
insulin resistance19,20. moreover, the accumulation of
adipose tissue macrophages is proportional to adipos-
ity in both humans and mice19,20, and sustained weight
loss results in a reduction in the number of adipose
tissue macrophages that is accompanied by a decrease
in the pro-inflammatory profiles of obese individuals21.
macrophages are also more abundant in visceral than
subcutaneous adipose tissue22, and this is in line with the
belief that visceral adipose tissue has a more important
role in the development of insulin resistance. However, it
has been recently reported that macrophages accumulate
in adipose tissues during the early phase of weight loss,
presumably as a result of adipose tissue lipolysis23.
Adipose tissue also contains fibroblasts, which pro-
duce extracellular matrix components. Recently, it has
been shown that metabolically dysfunctional adipose tis-
sue produces excess matrix components that may interfere
with adipose mass expansion and contribute to metabolic
dysregulation24. Thus, it is becoming increasingly evident
that intercellular communication within adipose tissue is
required for normal metabolic function. Examples of such
intercellular communication include the counter-regula-
tion between the adipocyte-derived anti-inflammatory
factors adiponectin and secreted frizzled-related protein 5
(sFRP5) and the macrophage-derived pro-inflammatory
factors TNF and wNT5a. under conditions of obesity,
TNF and wNT5a are upregulated, whereas adiponectin
and sFRP5 are downregulated3,4,25 (fIG. 2b).
Figure 1 | Adipose tissue depots. Adipose tissue is mainly found in subcutaneous
and visceral depots. Under conditions of obesity, adipose tissue expands in these and
other depots throughout the body. Common sites of adipose tissue accumulation
include the heart, the kidneys and the adventitia of blood vessels. Differential
adipokine secretion by various adipose tissue depots may selectively affect organ
function and systemic metabolism.
86 | FEbRuARy 2011 | vOLumE 11
© 2011 Macmillan Publishers Limited. All rights reserved
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The authors are funded by US National Institutes of Health
grants (AG34972, HL86785, AG15052 and HL81587).
Competing interests statement
The authors declare no competing financial interests.
NATuRE REvIEws | Immunology
vOLumE 11 | FEbRuARy 2011 | 97
focus on metabolism and immunology
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