| Abstract |
In the past, adipose tissue was considered just the energy storage of the organism: a totally inactive tissue capable only to store and release lipids according to metabolic body needs. Within the past decade though, our knowledge on the functions of the adipose tissue has completely changed the way the scientific community approaches the subject. It has been proven without doubt that the adipose tissue is a particularly metabolic and endocrine organ, able to produce and release to the circulation numerous hormones and cytokines, that are collectively called adipokines. Adipokines seem to play a major role in controlling appetite (through their actions on the Central Nervous System), in modulating inflammatory responses (since most of them can act as pro-inflammatory or even anti-inflammatory molecules), even on glucose metabolism.
Inflammatory Bowel Diseases (IBDs) is a general term that includes diseases with a wide spectrum of symptoms of the Gastrointestinal (GI) Tract. Namely, it includes Ulcerative Colitis and Crohn’s Disease, two separate clinical entities sharing the intense inflammation of the GI Tract, some molecular characteristics, but numerous differences in multiple levels as well. One interesting characteristic of Crohn’s Disease, without any similar observations in Ulcerative Colitis, is the accumulation of mesenteric fat wrapping the inflamed parts of the intestine, the so called “creeping” fat. This “creeping” fat has been the sign of the limits of the inflammation used for decades by surgeons that had to operate on Crohn’s patients. When it comes to Ulcerative Colitis, similar observations of the fat or research on it has not been performed.
The neuropeptide Substance P (SP), which is mostly found in the Central and Peripheral Nervous System, the Enteric Nervous System and the Immune System, has been found to be increased in the blood serum of patients and animal models of IBD, as well as the enteric epithelium at different stages, and has been suspected to have both aggravating and ameliorating effects. It has
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also been shown that the nerve endings that release SP seem to be increased in the fat tissue of animal models of IBD.
However, in spite of those data, the effects (and most importantly the mechanisms behind the possible effects) of SP on healthy and IBD patients’ adipose tissue has not been dissected. Only the existence of SP’s receptor and the effect of SP on obese patients’ preadipocytes has been examined in the past. The purpose of the present study is to unravel the previously mentioned possible effects.
Using the cell line 3T3-L1, mesenteric pre-adipocytes from rats, as well as human mesenteric preadipocytes and differentiated adipocytes from human healthy subjects and patients with IBD, the effects of SP treatment on transcriptional (mostly concerning NK1R, the rest of the receptors, adhesion molecules and cytokines) and protein (concerning mostly transcription factors that play role in adipocyte differentiation and adhesion molecules) levels were examined. Additionally, a pioneering system aiming to lead to the creation of one inducible and truly fat-specific animal model was successfully tested.
The results coming from the study of 3T3-L1s are conflicting and the assumption was made that the specific batch used was extremely unsteady for some reason. The results from rat mesenteric preadipocytes suggest response of those cells to SP stimulation, which, however, may not be mediated through SP-NK1R interaction. Human mesenteric preadipocytes´ results tend to support differences in the expression levels of the NK1R, as well as differences amongst the responses to SP between control and IBD samples, undifferentiated and differentiated cells and the stages of the disease. Concerning the rat mesenteric preadipocytes and the human cells, a larger amount of samples will be needed to draw safe conclusions. The successful trial of the new fat-specific lenti-virus brings us a step closer to achieving the creation of the first truly inducible fat-specific animal model which will be a useful tool for the following studies.
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Effects of substance P on preadipocyte and adipocyte expression
