Gorana Rančić

Triactome: Neuro–Immune–Adipose Interactions. Implication in Vascular Biology

Understanding how the precise interactions of nerves, immune cells, and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue (PAAT), we recently designated tunica adiposa (in brief, adiposa like intima, media, and adventitia). Today, atherosclerosis is considered an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy, and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. PAAT expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic) signaling proteins collectively dubbed adipokines. However, the role of vascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro–immune–adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

An Integrated View: Neuroadipocrinology of Diabesity

ABSTRACT Today’s achievements in systems biology and -omics sciences have facilitated a shift from studying individual molecules and tissues to characterising molecules and cells holistically. In this article, we attempt to discuss the status of a much-needed coherent view that integrates studies on neurobiology and adipobiology, as well as those on diabetes and obesity. Globally, cardiometabolic diseases (atherosclerosis, hypertension, type 2 diabetes mellitus, obesity, diabesity, and metabolic syndrome) are the most prevalent pathologies. In 2000, Astrup and Finer (Obes Rev 1: 57-59) wrote the following: “Since type 2 diabetes is obesity dependent, and obesity is the main aetiogical cause of type 2 diabetes, we propose the term ‘diabesity’ should be adopted.” Arguably, the research field of adipobiology has witnessed three major paradigm shifts since the discovery of leptin, an adipose-derived hormone, in 1994. Various neuroendocrine and neurotrophic factors are included in the growing list of endocrine and paracrine adipose-secreted signaling proteins collectively designated adipokines. These findings open a novel field of research known as neuroadipocrinology, a component of neuroendocrinology. Adipokines, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), mediate multiple biological processes, such as food intake, immunity, inflammation, memory, mood, and metabolism. The effects on metabolism involve the maintenance of glucose, lipid and energy homeostasis as well as cardioprotection, neuroprotection, and aging. In this article, we highlight the role of metabotrophic factors (MTF) and the adipose- and nonadipose-derived biomolecules that mediate these effects. Recent results demonstrate that circulating and tissue levels of certain MTFs, e.g., adiponectin, NGF, BDNF, glucagon-like protein-1, sirtuin-1, interleukin- 10, and aquaporin-7, are altered in cardiometabolic diseases, including diabesity. Overall, this may cultivate a novel thinking for diabesity, herein also referred to as Homo diabesus. SAŽETAK Današnja dostignuća u biologiji sistema i povezanim biološkim naukama omogućila su prelazak sa proučavanja pojedinačnog molekula i tkiva na holistički prikaz molekula i ćelija. Ovde pokušavamo da objasnimo koherentan prikaz koji integriše studije neurobiologije i adipobiologije, kao i one o dijabetesu i gojaznosti. Uopšteno, kardiometaboličke bolesti (ateroskleroza, hipertenzija, dijabetes melitus tip 2, gojaznost, diabesity (dijabetes melitus tip 2 udružen sa gojaznošću), i metabolički sindrom) predstavljaju najčešća oboljenja današnjice. 2000. godine Astrup i Finer (Obes Rev 1: 57-59) su napisali : “Obzirom da dijabetes melitus tip 2 zavisi od gojaznosti, a gojaznost je glavni etiološki uzrok dijabetesa tip 2, predlažemo da se termin ‘diabesity’ usvoji.” Verovatno je polje istraživanja adipobiologije svedočilo o tri velike promene od otkrića leptina, hormona adipoznog porekla, 1994.godine. Različiti neuroendokrini i neurotrofični faktori su takođe bili uključeni u povećanje liste endokrinih i parakrinih signalnih proteina sekretovanih od strane adipocita koji zajedno čine adipokine. Ovi nalazi otvaraju novu oblast istraživanja, neuroadipokrinologiju, deo neuroendokrinologije. Adipokini, uključujući faktor rasta nerava (NGF) i neurotrofični faktor poreklom iz mozga (BDNF), posreduju u višestrukim biološkim procesima kao što su unos hrane, imunitet, inflamacija, pamćenje, raspoloženje i metaboliza. Efekti na metabolizam uključuju održavanje glukoze, lipida i energetske homeostaze, kao i kardioprotekciju, neuroprotekciju i starenje. Ovde izdvajamo ulogu metabotropnog faktora (MTF), biomolekula poreklom iz masti, kao i biomolekula koji ne vode poreklo iz masti, koji posreduju ove efekte. Nedavni rezultati pokazuju da se cirkulišući i/ili tkivni nivoi nekog MTF, na primer adiponektin, NGF, BDNF, glukagonu sličan protein-1, sirtuin- 1, interleukin- 10, akvaporin-7, menjaju u kardiometaboličkim bolestima, uključujući diabesity. Uopšteno, ovo može otvoriti nov pristup u razmišljanju o dijabetesu tip 2 udruženim sa gojaznošću, koji se takođe ovde označava kao i Homo diabesus.

Adipoparacrinology of Atherosclerosis: Evidence Updated

Abstract: Recently, the secretory - endocrine, paracrine and autocrine - phenotype of adipose tissue, consisting of adipo-cytes, stromovascular cells and immune cells, has increasingly been recognized. In humans, adipose tissue is partitioned into two large depots (subcutaneous and visceral) and many small depots associated with heart, blood vessels, major lymph nodes, pancreas, prostate gland, ovaries. Accordingly, two major subfields of adipobiology have emerged, adi-poendocrinology (studying the endocrine activity of adipose tissue) and adipoparacrinology (studying the paracrine activ-ity of adipose tissue). Traditional concept of the pathogenesis of atherosclerosis focuses on intimal surface, where endo-thelial dysfunction expressed by an “inside-out” inflammatory process triggers the formation of atherosclerotic plaque. The present short review highlights evidence for the possible role of dysfunctional paracrine activity of epicardial adipose tissue and of periadventitial adipose tissue in an “outside-in” pathway in the development of coronary and peripheral athe-rosclerosis, respectively. Such a paradigm may have various therapeutic applications including in coronary artery bypass surgery.