Blackwell Publishing LtdOxford, UKOBRObesity Reviews1467-7881© 2007 Queen’s Printer and Controller of HMSO; published with permission; Journal

compilation © 2007 The

International Association for the Study of Obesity? 20078••4144Review ArticleAdipocyte biology P. Trayhurn

obesity reviews

Adipocyte biology

P. Trayhurn

Obesity Biology Unit, University of Liverpool, Keywords: Adipokines, inflammation, obesity, white adipose tissue
Liverpool, UK

Accepted 12 November 2006

Address for correspondence: Professor P

Trayhurn, Obesity Biology Unit, School of
Clinical Sciences, University of Liverpool, 3rd
Floor UCD Building, Liverpool L69 3GA, UK.
E-mail: p.trayhurn@liverpool.ac.uk

OnlineOpen: This article is available free online at www.blackwell-synergy.com obesity reviews (2007) 8 (Suppl. 1), 41–44

tissues – brown and white adipose tissue. Brown adipose

Background
tissue is specialized for heat production by non-shivering
Obesity is fundamentally a problem of energy balance – thermogenesis, and in this tissue the stored lipid droplets
irrespective of the underlying social, cultural, behavioural serve primarily as a fuel for the production of heat. In white
and genetic determinants. As such, it can only develop adipose tissue, on the other hand, the stored triacylglycer-
when energy (food) intake is in excess of total energy ols provide a long-term fuel reserve for the animal. Indeed,
expenditure (Basal Metabolic Rate, ‘thermogenesis’, white fat is the main energy reservoir in mammals, triacyl-
physical activity, ‘non-exercise activity thermogenesis’). glycerols providing fuel storage at a high energy density,
Differences between intake and expenditure are primarily both because of the considerable caloric value of lipid
buffered by changes in the amount of lipid (triacylglycerols) (39.1 kJ g−1 vs. 15.4–17.5 kJ g−1 for carbohydrate) and
deposited in the specialized fuel storage organ, white adi- because, in contrast to carbohydrates, triacylglycerols can
pose tissue (or white fat). Until recently, research on energy be stored with little associated water. The result is that up
balance and obesity focused particularly on the central to 85% of the weight of adipocytes consists of lipid.
neuroendocrine pathways involved in the hypothalamic In addition to fuel storage, white adipose tissue can act
control of food intake and on the peripheral mechanisms as a thermal insulator and protect other organs from
of adaptive energy expenditure. White adipose tissue, mechanical damage. Two further features of the tissue
however, attracted little research interest. should be highlighted. First, unlike most other organs,
Adipose tissue has now moved centre stage in obesity white fat is distributed in multiple depots in the body, both
research, there having been a revolution in our understand- subcutaneously and internally, and clusters of adipocytes
ing of the biological role of the tissue over the past decade. may also be located adjacent to, or embedded in, other
Indeed, adipose tissue biology is currently one of the ‘hot’ organs such as the lymph nodes and skeletal muscle. A
areas of biomedical science – principally because it is now second important feature is that adipose tissue is not made
recognized as a major endocrine and signalling organ. up simply of mature adipocytes, which store the lipid, but
contains a variety of other cells (e.g. fibroblasts, endothelial
cells, macrophages) which constitute around 50% of the
Characteristics of white adipose tissue
total cellular content. From the functional viewpoint, it is,
White adipose tissue is part of what Cinti has termed ‘the of course, the mature adipocytes that are the pivotal cells
adipose organ’, which consists of two functionally distinct within adipose tissue.

This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry
© 2007 Queen’s Printer and Controller of HMSO; published with permission
Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 41–44 41
42 Adipocyte biology P. Trayhurn obesity reviews

in the genetically obese (ob/ob) mouse, was the pivotal

The focus on white adipose tissue
discovery which led to the realization that adipose tissue is
There are several reasons why the role of white adipose a critical endocrine organ. Leptin is an essential signal from
tissue in energy balance and obesity research has become a adipocytes to the hypothalamus in the control of appetite
current focus of research. An obvious point that has been and energy balance. Indeed, without functional leptin,
ignored until recently is that obesity is defined by the severe obesity ensues as in the ob/ob mouse and the human
expansion of adipose tissue mass and it must therefore be homologues that have been described. Leptin is in practice
central to our understanding of obesity. More specifically, a pleiotropic hormone, its functions extending far wider
adipose tissue is now recognized as the source of key hor- than appetite and energy balance to encompass a multiplic-
mones which play an important role in the regulation of ity of actions, including acting as a signal in reproduction
energy balance – particularly leptin – and adipocytes are and immunity.
today recognized as secreting a diverse range of protein Much attention has also been focused on adiponectin,
factors and signals termed ‘adipokines’, which are involved which is a hormone produced exclusively by adipocytes. In
in overall metabolic regulation and increasingly considered contrast to most adipokines, and leptin in particular, the
to be directly linked to the pathologies associated with expression and circulating levels of adiponectin fall in obe-
obesity. sity. A number of roles are attributed to adiponectin,
including the modulation of insulin sensitivity and vascular
function, as well as an anti-inflammatory action. Adiponec-
White adipocytes
tin, like leptin, is a powerful example of an adipocyte-
White adipocytes are major secretory cells, making adi- derived hormone which interacts with other organs and
pose tissue a key endocrine organ. Indeed, adipose tissue is a wide range of physiological systems and metabolic
the largest endocrine organ in most humans – and cer- processes.
tainly so in the overweight and obese. For example, in a
lean individual [body mass index (BMI) 22–23], approxi-
Inflammation and obesity
mately 20% of total body weight is adipose tissue, while
in an obese subject (BMI 30) almost half of body weight is A number of inflammation-related proteins are released by
due to the tissue. There is a clear implication that even white adipocytes, as well as adiponectin, and these include
minor metabolic changes in such a large secretory organ cytokines, chemokines and acute phase proteins. In addi-
have the potential to impact broadly on the body as a tion to these factors, several other inflammation-related
whole. adipokines are recognized, including leptin and the angio-
Quantitatively, the most important secretion from adipo- genic protein, vascular endothelial growth factor. In obe-
cytes is fatty acids, of which there is net release at periods sity, the production of many of these adipokines increases
of negative energy balance (particularly fasting). In addi- markedly and the tissue is in effect ‘inflamed’.
tion to fatty acids, several other lipid moieties are released One of the most important recent developments in obe-
by fat cells; these include prostanoids, which are synthe- sity research is the emergence of the concept that obesity
sized by the tissue, and cholesterol and retinol, which are is characterized by chronic mild inflammation – paralleling
not synthesized but rather are stored and subsequently the situation with other diseases. The basis for this view is
released. In addition, certain steroid hormone conversions that the circulating level of several cytokines and acute
can take place within white adipocytes. phase proteins associated with inflammation is increased in
The ‘new’ component of the ‘secretome’ of adipocytes is the obese. As adipocytes secrete a number of cytokines and
the wide range of protein factors and signals that are acute phase proteins, it is considered that the expanded
released. These ‘adipokines’ (or ‘adipocytokines’) now adipose tissue mass contributes, either directly or indirectly,
number in excess of 50 different molecular entities. to the increased production and circulating levels of inflam-
mation-related factors in obesity. In other words, the state
of inflammation in adipose tissue in obesity leads to an
The adipokines
increased production and release of inflammation-related
The adipokines are highly diverse in terms of protein struc- factors.
ture and physiological function. They include classical Close links, and even similarities, between adipocytes
cytokines, growth factors and proteins of the alternative and immune cells are increasingly evident. The inflamma-
complement system; they also include proteins involved in tory state of adipose tissue in obesity has been high-
the regulation of blood pressure, vascular haemostasis, lighted by recent reports demonstrating that there is
lipid metabolism, glucose homeostasis and angiogenesis. extensive infiltration of the tissue by macrophages in the
Leptin is the adipokine which has received most atten- obese. The arrival of macrophages is thought to lead to a
tion. Its discovery in 1994, as the product of the Ob gene considerable amplification of the inflammatory state in

This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry
© 2007 Queen’s Printer and Controller of HMSO; published with permission
Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 41–44
obesity reviews Adipocyte biology P. Trayhurn 43

white fat, through the cytokines and chemokines that • understanding the mechanistic basis for inflammation
they secrete. of adipose tissue in obesity.

Adipose tissue and the diseases of obesity Additional areas of particular interest include an em-
phasis on the importance of blood flow to adipose tissue
The central change to the body in obesity is clearly the function and dysfunction, and the concept that, as with
increase in the amount of adipose tissue – which may tumours, manipulation of angiogenesis could lead to a loss
constitute more than half of total body mass in those of body fat.
with a BMI that is in excess of the threshold of obesity. It
is not, however, only the total amount of fat that is
important, but also its distribution. Thus, a more central Long-term perspective
fat deposition (‘android’ or ‘apples’, as opposed to A key area for the next few years will undoubtedly be
‘gynoid’ or ‘pears’) is associated with a greater risk of the unravelling the role of inflammation in the development of
metabolic syndrome and several of the other diseases obesity-related diseases – not only type 2 diabetes and the
linked to obesity. A key question is why visceral fat is metabolic syndrome, but also cancer. Indeed, major insight
particularly significant in terms of obesity-associated into the causes of cancer may come from investigating the
disorders, and a long-standing position is that it is the mechanistic link between adiposity and the development of
proximity to the liver and the portal circulation that is tumours – and would be expected to lead to new opportu-
important. nities for therapeutic intervention.
The current view is that the inflammatory state of obesity Predicting beyond the next decade is inevitably both
plays a key causal role in the development of type 2 diabe- difficult and hazardous, a situation amply illustrated by the
tes and the metabolic syndrome (which includes atheroscle- fact that 20 years ago it was never envisaged that adipose
rosis, hypertension and hyperlipidaemia) associated with tissue might be an important endocrine organ. Neverthe-
obesity. A central hypothesis is that it is the increases in less, realistic scenarios within the existing paradigms can
inflammation-related adipokine production that occur in be entertained.
obesity that lead to the associated diseases. In this context, For example, treatment of obesity-related diseases might
the reduction in adiponectin in the obese is thought to be be possible if the production and/or action of specific adi-
of particular significance in view of the anti-inflammatory pokines, particularly those linked to inflammation, were to
effect of this adipokine. Alterations in fatty acid flux have be targeted. There are already potential routes through
also been implicated. which this might be achieved. Pharmacologically based
approaches include harnessing the anti-inflammatory
Current research foci action of the new generation of anti-diabetic drugs – the
thiazolidinediones – which operate through the PPARγ
As emphasized above, adipocyte biology is now a ‘hot’ area
nuclear receptor. Nutritional intervention could also be
of biomedical research. Much of the work centres on the
envisaged through anti-inflammatory n-3 polyunsaturated
secreted protein signals and the secretory role of the tissue,
fatty acids.
and it also includes the potential links between fatty acids
Nutritional genomics is likely to lead to the possibility
and the metabolic syndrome.
of individualized dietary advice based on genetic profiling
The key current areas of research are:
(specific polymorphisms); this could potentially be har-
• the identification of the full range of proteins secreted nessed in terms of the modulation of adipokine production
from fat cells – the ‘adipokinome’; to minimize disease risk. New appetite and energy balance
• describing the physiological processes with which the signals emanating from adipose tissue may be discovered,
adipokines are involved, and the extent to which adipo- which could be targeted to inhibit appetite. A better under-
cytes are in ‘conversation’ with other cells, organs and standing of the basis for functional differences between
metabolic systems; adipocytes in different depots (whether intrinsic or a reflec-
• identification of the changes in the secretion of specific tion of local conditions) may lead to the possibility of
proteins when adipose tissue mass expands – and deter- manipulating cells in detrimental depots – primarily vis-
mining the potential pathological consequences of such ceral – towards those in more benign depots.
changes; The concepts established through work on obesity will
• the specific role of inflammation-related adipokines in flow to other areas – such as ‘healthy ageing’. Some of the
the development of type 2 diabetes and the metabolic diseases of ageing, such as the metabolic syndrome and the
syndrome; dementias, are linked to inflammation and it is speculated
• the importance of macrophages in modulating adipose that adipose tissue, through various adipokines, may play
tissue function in obesity; an important and unexpected role in the aetiology of these

This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry
© 2007 Queen’s Printer and Controller of HMSO; published with permission
Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 41–44
44 Adipocyte biology P. Trayhurn obesity reviews

diseases. This will be of special significance to an ageing 7. Harris RB. Leptin – much more than a satiety signal. Annu Rev
population and provides a potent example of how growing Nutr 2000; 20: 45–75.
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knowledge of adipocyte biology is likely to impact in quite
Clin Endocrinol Metab 2004; 89: 2548–2556.
unexpected ways on other areas and issues beyond obesity. 9. Lazar MA. How obesity causes diabetes: not a tall tale. Science
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Conflict of Interest Statement 10. Matsuzawa Y. Adipocytokines and metabolic syndrome.
Semin Vasc Med 2005; 5: 34–39.
No conflict of interest was declared. 11. Pond CM. Adipose tissue and the immune system. Prostag-
landins Leukot Essent Fatty Acids 2005; 73: 17–30.
Further reading 12. Rajala MW, Scherer PE. The adipocyte – at the crossroads of
energy homeostasis, inflammation, and atherosclerosis. Endocri-
1. Ahima RS. Central actions of adipocyte hormones. Trends nology 2003; 144: 3765–3773.
Endocrinol Metab 2005; 16: 307–313. 13. Trayhurn P. Endocrine and signalling role of adipose tissue:
2. Berg AH, Scherer PE. Adipose tissue, inflammation, and car- new perspectives on fat. Acta Physiol Scand 2005; 184: 285–293.
diovascular disease. Circ Res 2005; 96: 939–949. 14. Trayhurn P, Beattie JH. Physiological role of adipose tissue:
3. Cinti S. The adipose organ: morphological perspectives of white adipose tissue as an endocrine and secretory organ. Proc
adipose tissues. Proc Nutr Soc 2001; 60: 319–328. Nutr Soc 2001; 60: 329–339.
4. Das UN. Is obesity an inflammatory condition? Nutrition 2001; 15. Trayhurn P, Wood IS. Adipokines: inflammation and the
17: 953–966. pleiotropic role of white adipose tissue. Br J Nut 2004; 92: 347–
5. Frayn KN, Karpe F, Fielding BA, Macdonald IA, Coppack SW. 355.
Integrative physiology of human adipose tissue. Int J Obes 2003; 16. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory
27: 875–888. changes in adipose tissue. J Clin Invest 2003; 112: 1785–1788.
6. Frühbeck G, Gómez-Ambrosi J, Muruzabal FJ, Burrell MA. 17. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabe-
The adipocyte: a model for integration of endocrine and metabolic tes. J Clin Invest 2005; 115: 1111–1119.
signaling in energy metabolism regulation. Am J Physiol Endo- 18. Yudkin JS. Adipose tissue, insulin action and vascular disease:
crinol Metab 2001; 280: E827–E847. inflammatory signals. Int J Obes 2003; 27(Suppl. 3): S25–S28.

This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry
© 2007 Queen’s Printer and Controller of HMSO; published with permission
Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 41–44