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Adipose Tissue

 

The regulation of energy homeostasis is highly complex, and is central to understanding the disorders of body weight, particularly obesity. The mechanisms by which food intake is regulated, particularly the central neuroendocrine systems involved in appetite, and the components of energy expenditure and their metabolic plasticity, have traditionally been the primary focus of studies on energy balance. However, very recently white adipose tissue (WAT) has become a key focus. This reflects the major change in perspectives on energy regulation and adipose tissue function that occurred following the discovery of the cytokine-like hormone, leptin in 1994.

 

 

WAT

 

In addition to fuel storage, WAT can act as a thermal insulator and protect other organs from mechanical damage. The tissue is distributed in multiple depots, both subcutaneously and internally, and clusters of adipocytes may also be located adjacent to, or embedded in, other organs such as the lymph nodes and skeletal muscle. WAT does not consist simply of mature adipocytes, which store triacylglycerols; there are a variety of other cells (e.g. fibroblasts, endothelial cells, macrophages) which constitute around 50% of the total cellular content.

 

 

Adipokines

 

With the discovery of leptin, WAT has become recognised as a dynamic endocrine organ involved in a wide range of physiological systems and metabolic processes, with extensive cross talk with other tissues and organs. White adipocytes are recognised to secrete several major hormones additional to leptin, notably adiponectin, together with a range of other protein signals and factors termed ‘adipokines’ (or adipocytokines). The adipokines, which now number >50 different molecular entities, are highly diverse in terms of structure and function, and include proteins involved in lipid metabolism, insulin sensitivity, vascular function and blood pressure regulation. Importantly, a number of adipokines are directly linked to immunity and the inflammatory response; these include cytokines, chemokines and acute phase proteins, as well as other inflammation-related proteins.

 

 

Obesity

 

A marked increase in the production of inflammation-related adipokines occurs when WAT mass is increased in obesity. This suggests that WAT contributes directly to the elevated circulating level of the inflammation-related factors in the obese, obesity being characterised by a state of chronic low-grade inflammation. A major exception is adiponectin, which has an anti-inflammatory action, the circulating level of which falls with elevated WAT mass. It is increasingly considered that inflammation may be causal in the insulin resistance, hyperlipidaemia and vascular disease that develop as part of the spectrum of disorders associated with obesity. The changes in adipokine secretion are considered to link directly to the alterations in insulin sensitivity and vascular function; for example, TNFα modulates the insulin sensitivity of adipocytes, while adiponectin is implicated in both insulin sensitivity and vascular function. The link between adipose tissue and inflammation has been augmented by the recent evidence that WAT is infiltrated by macrophages in the obese, and this may be a significant component of the inflammatory state within expanding adipose tissue depots.

 

Adipose tissue biology, currently a ‘hot area’ of biomedical research, has benefited greatly from genomic and post-genomic approaches. The central role of the tissue in nutrition makes it fertile ground for the continuing application of nutritional genomics.  Specifically, variation in genes encoding the adipokines will alter an individual’s susceptibility to obesity by altering expression of the genes and/or their activities.

 

Reviews

 

  • Trayhurn P (2005) Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand 184, 285-293. PMID: 16026420

 

  • Trayhurn P & Wood IS (2005) Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans 33, 1078-1081. PMID: 16246049 Free Access

 

  • Agarwal AK, Garg A. (2006) Genetic Disorders of Adipose Tissue Development, Differentiation, and Death. Annual Rev Genomics Hum Genet. 2006 May 24 (epub).  PMID: 16722806

 

  • Schaffler A, Muller-Ladner U, Scholmerich J, Buchler C. (2006) Role of the adipose tissue as an inflammatory organ in human diseases.  Endocr Rev. May 9 (epub); PMID: 16684901

Links

 

 

Contributed by Paul Trayhurn Unviersity of Liverpool, United Kingdom (July 2006)

 

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