Adipose tissue is now regarded as an endocrine tissue critically involved in many aspects of metabolism and reproduction. Fat tissue produces adipokines that behave not only as secretory molecules, but also as autocrine/paracrine factors in complex signaling networks, which are involved in the control of metabolism and the immune response. Adipose tissue is also intimately interspersed within many tissues (e.g., liver, muscle, heart) and may function as “miniorgans” with specific paracrine effects. However, fat is not the only source of adipokines and we provided novel evidence that adipokines such as leptin are also expressed in the brain. We now hypothesize that the converse is also true: i.e., peptides normally assumed to be specifically of brain or hypothalamic origin should be expressed in adipose tissue. In fact, gene expression profiling of human fat revealed the presence of several neuropeptide transcripts, such as NPY, which are normally associated with hypothalamic function. Receptors for such peptides are also present in adipocytes suggesting the existence of local autocrine or paracrine feedback loops. This chapter will review the evidence that adipose tissue should be considered as a local source of neuropeptides.
We begin by outlining our data that kiss1, currently a worldwide clinical research focus in the control of fertility, is expressed and regulated in adipose tissue. Of particular interest are our findings that kiss1 expression in fat tissue is regulated differently to that in hypothalamus. Adipose kiss1 expression may therefore be an important link between, for example, anorexia nervosa and infertility. A second example is angiotensin II, a prototypical ectopic neuropeptide derived from the conversion of angiotensinogen, which is commonly regarded as a systemic hormonal peptide for maintaining volume and blood pressure homeostasis, and which is also a product of adipose tissue. The presence of angiotensin II receptors in fat further suggests a local autocrine/paracrine system. Evidence indicates that this system may also be a useful therapeutic target in the treatment of obesity and diabetes. Other examples, discussed in detail, are NPY, NGF, prolactin, and atrial natriuretic peptide. We outline the evidence for their expression in fat tissue, if they are released from adipocytes, and whether their receptors are also present. As noted for kiss1, the regulation of gene expression of these peptides, in adipose tissue, is different to that seen in other tissues. The possibility exists to specifically target adipocyte expression of neuropeptides for therapeutic purposes, for example, in the treatment of obesity, diabetes, and infertility.
Adipose Tissue Nerve Growth Factor Atrial Natriuretic Peptide Prolactin Release Body Mass Index
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Angiotensin II receptor 1
Body mass index
Cyclic adenosine monophosphate
Cocaine and amphetamine regulated transcript
Complementary deoxyribonucleic acid
Cyclic guanosine monophosphate
Corticotrophin releasing factor
Dopamine receptor 2
Fasting-induced adipose factor
G protein coupled receptor 54
Insulin like growth factor 1
Messenger ribonucleic acid
Nerve growth factor
Neuropeptide Y receptor
Polycystic ovarian syndrome
Peroxisome proliferator-activated receptor gamma
Reverse transcriptase-polymerase chain reaction
Transforming growth factor beta
Tumor necrosis factor alpha
Tyrosine kinase receptor A
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The studies in our laboratory were funded by the NSHRF, the IWK Health Centre, the IWK Auxiliary, the Atlee Endowment, and UIMRF/Capital Health. Dr. Brown was supported by an NSHRF Graduate Studentship. The authors are especially indebted to Diane Wilkinson, for technical assistance, and P.M.H. Wilkinson for creation of the figures.