Serum levels of acetylcholinesterase in metabolic syndrome

It is known today that low grade inflammatory mechanisms play a pivotal role in the pathogenesis of cardiometabolic diseases including the metabolic syndrome (1-4). In the same vein, in addition to its role in cholinergic neurotransmission, acetylcholine exerts a potential anti-inflammatory effect mediated by `cholinergic anti-inflammatory reflex` (5). Accordingly, a positive correlation of the blood serum level of acetylcholinesterase, butyrylcholinesterase and C-reactive protein (CRP) was reported in obese and diabetic patients (6-10)

Neurobiology of adipose tissue

Adipose tissue's secretory phenotype paradigm shift has been upregulating since December 1, 1994, the birthday of leptin, an endocrine signaling protein (adipokine), which triggered the development of adipoendocrinology. Today, more than hundred adipokines are identified. Here an update of adipose-derived neurotrophic factors and neuropeptides and their receptors is presented, raising a hypothesis of neuroendocrine potential of this dynamic tissue.Biomedical Reviews 2008; 19: 45-48

Submandibular glands in the metabolic syndrome

In addition to their stimulatory action on neuronal differentiation and survival, a variety of neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor, exert metabotrophic effects, including improvement of glucose, lipid and energy homeostasis. It was recently reported that plasma levels of both NGF and BDNF are reduced in patients with advanced metabolic syndrome and with acute coronary syndromes, and that NGF tissue content is decreased in human atherosclerotic coronary arteries. Since NGF and BDNF are synthesized, stored, and released by submandibular salivary glands, we investigated the structure and function of these glands. Here we present our scintigraphic and echographic results of submandibular glands of patients with advanced stage of metabolic syndrome: (i) scintigraphic analysis using the radiotracer (99m)Tc-pertechnetate showed an inhibition of salivary gland excretory activity, and (ii) echographic evaluation revealed a parenchymal destruction and a prominent fibrosis of the glands. Both suggestive for the involvement of submandibular glands in decreased secretion of NGF and BDNF as implicated in the pathogenesis of metabolic syndrome.Biomedical Reviews 2007; 18: 65-67

Leptin 21 years later: From fat`s big bang to central stage never before has adipose tissue been so active

Here we focus on Fat`s Big Bang exploring officially by the discovery of leptin by Jeffrey Friedman and colleagues on 1 December 1994 in Nature. We recall their journey of discovery and discuss perspective on the further research in adipobiology and adipopharmacology of cardiometabolic, neuropsychiatric and cancer diseases. Friedman`s seminal discovery makes a paradigm shift in our knowledge of adipose tissue biology - from merely a fat storage and metabolizer to a major endocrine and paracrine organ of the human body, producing more than 600 signaling proteins collectively termed adipokines. Leptin thus became the fundament in the obesity research and related diseases.Adipobiology 2015; 7: 9-13Key words: adipose tissue, adipokines, adipobiology, Jeffrey M. Friedman, leptin, disease, therap

NGF-ome: its metabotrophic expression. Homage to Rita Levi-Montalcini

Nowadays, in the postgenome time, many "-ome" studies have emerged including proteome, transcriptome, interactome, metabolome, adipokinome, connectome. In this vein, the catchall term NGF-ome embodies all the actions of NGF in health and disease. Accordingly, the present Festschrift, also tabula gratulatoria, is to honor and acknowledge the contributions of the distinguished neuroscientist and magistra Rita Levi-Montalcini, the Nobel Prize winner-1986 for the discoverer of NGF. Today, NGF and another neurotrophin, brain-derived neuroptrophic factor (BDNF), are well recognized to mediate multiple biological phenomena, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. These latter effects are involved in the maintenance of cardiometabolic homeostasis (glucose and lipid metabolism as well as energy balance, and cardioprotection). Circulating and/or tissue levels of NGF and BDNF are altered in cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes, metabolic syndrome, and type 3 diabetes/Alzheimer's disease). A hypothesis thus emerged that a metabotrophic deficit due to the reduction of NGF/BDNF availability and/or utilization may be implicated in the pathogenesis of cariometabolic and neurodegenerative diseases. The present challenge is therefore to cultivate a metabotrophic thinking about how we can modulate NGF/BDNF secretion and signaling for the benefit of human cardiometabolic and mood health.Biomedical Reviews 2010; 21: 25-29

In the heart of adipobiology: cardiometabolic disease

Published on 1 December 1994 issue of Nature, the Jeffrey Friedman's discovery "gave leptin in the beginning" of the endocrine saga of adipose tissue. Onwards, studies on this tissue have enjoyed an explosive growth that conceptualized a novel field of research, adipobiology. Arguably, in the heart of adipobiology and adipopharmacology are studies focusing on the pathogenesis, prevention and therapy of cardiometabolic diseases (CMD) including atherosclerosis, hypertension, obesity, type 2 diabetes, metabolic syndrome (global cardiometabolic risk), and lipodystrophies.Biomedical Reviews 2009; 20: 1-5

SOS for Homo sapiens obesus

Published on 1 December 1994 issue of Nature, the Jeffrey Friedman's discovery "gave leptin in the beginning" of the endocrine saga of adipose tissue. Onwards, studies on this tissue have enjoyed an explosive growth that conceptualized a novel field of research, adipobiology. Arguably, in the heart of adipobiology and adipopharmacology are studies focusing on the pathogenesis, prevention and therapy of cardiometabolic diseases (CMD) including atherosclerosis, hypertension, obesity, type 2 diabetes, metabolic syndrome (global cardiometabolic risk), and lipodystrophies.Adipobiology 2010; 2: 5-8

The adipose tissue: a new member of the diffuse neuroendocrine system?

Adipose tissue is a sophisticated module, consisting of adipocytes and non-adipocyte cellular elements including stromal, vascular, nerve and immune cells. There is at present evidence that sharing of ligands and their receptors constitutes a molecular language of the human's body, which is also the case for adipose tissue and hypothalamus-pituitary gland. Historically, Nikolai Kulchitsky's identification of the enterochromaffin cell in 1897 formed the basis for the subsequent delineation of the diffuse neuroendocrine system (DNES) by Friedrich Feyrter in 1938. In DNES paradigm, the secretion of hormones, neuropeptides and neurotrophic factors is executed by cells disseminated throughout the body, for example, Kulchitsky (enterochromaffin) cells, testicular Leydig cells, and hepatic stellate cells. Here we propose that the adipose tissue might be a new member of DNES. Today (dnes, in Bulgarian), adipose tissue is "getting nervous" indeed: (i) synthesizes neuropeptides, neurotrophic factors, neurotransmitters, hypothalamic hormones/releasing factors and their receptors, (ii) like brain expresses endocannabinoids and amyloid precursor protein and, for steroidogenesis, the enzyme aromatase (P450arom), (iii) adipocytes may originate from the neural crest cells, and (iv) adipose-derived stem cells may differentiate into neuronal cells. Further molecular profiling of adipose tissue may provide new biological insights on its neuroendocrine potential. Overall this may frame a novel field of study, neuroadipobiology; its development and clinical application may contribute to the improvement of human's health.Adipobiology 2009; 1: 87-93

Adipoendocrinology and adipoparacrinology: emerging fields of study on the adipose tissue

Adipose tissue was conceived originally as merely passive, space-filling, fat storage tissue. However, in the last 10 years, investigations aimed at studying the endocrine secretion by adipose tissue have enjoyed explosive growth. The major secretory compartment of adipose tissue consists of adipocytes and stromal fibroblasts (adipofibroblasts). These cells secrete multiple bioactive molecules, conceptualized as adipokines or adipocytokines. Overall, this intellectual grown process framed an emerging field of study, adipoendocrinology. "Adipoendocrinology" connotes the study of the cellular and molecular biology of the endocrine function of adipose tissue in normal and diseased conditions. In humans, white adipose tissue is partitioned into a few large depots, including visceral and subcutaneous location, and many small depots, associated with heart, large blood vessels, major lymph nodes and other organs. The possibility that the endocrine secretory activity of large adipose depots may directly contribute to the elevated plasma levels of disease-associated adipokines has recently gained considerable attention. However, the paracrine secretory activity of organ-associated adipose tissue (the small adipose depots) has until now attracted little attention in the adipobiology of disease. Here we attempt to emphasize that studies aimed at evaluation of the paracrine secretion of organ-associated adipose tissue are becoming mandatory, since identification of the secreted molecules, particularly, adipokines, may yield clues to a possible transmission of pathogenic and/or protective stimuli, from the associated adipose tissue towards the interior of the associating organ. In this review we summarize most of the current information about adipoendocrinology and adipoparacrinology of various diseases.Biomedical Reviews 2001; 12: 31-39