The mast cell: Another master in adipoimmunology

Recently, a large number of studies focus on (i) adipose tissue endocrine and paracrine function, and (ii) adipose-immune interactions herein referred to as adipoimmunology. In effect, a wide range of signaling proteins, dubbed adipokines, was identified as endocrine and paracrine secretory products of adipocytes and associated stromal vascular cells, including macrophages, lymphocytes and mast cells, the latter being less evaluated as compare to the formers. During obesity immune cells migrate into adipose tissue and inflame it by the secretion of a large amount of adipokines and thus trigger the development of so-called low grade inflammation-related diseases. Based on Steve Galli`s concept of mast cell as master cells in many biological and pathological processes (New Engl J Meet 1993; 328:257-265), here we highlight recent studies on the significance of adipose mast cells in the pathogenesis and therapy of cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes mellitus, metabolic syndrome) and breast cancer. Knowledge of the master work of these cells may provide a background for mast cell-targeted pharmacology for low grade inflammation-related diseases.Adipobiology 2015; 7: 15-19Key words: adipose tissue, adipokines, atherosclerosis, breast cancer, inflammation, mast cells, obesit

PVAT and Atherogenesis: a Crossroad of White and Brown Adipobiology

In 1999, the prevailing response-to-injury hypothesis of Russell Ross stated that atherosclerosis is an inflammatory disease, leading - through an inside-out road - to endothelial and smooth muscle dysfunction resulting in the formation of atherosclerotic plaques. Accordingly, intima-media thickness became an accepted measure of structural vascular remodeling and a strong predictor of atherosclerosis. However, it is unlikely that such a road may solely travel the whole multiplex network like that of atherogenesis. Recently things changed dramatically and the attention was moved from inside-out to outside-in road emphasizing the role for adventitial and adipose dysfunction in the processes of atherogenesis

Colonic fermentation – more than meets the nose

Fermentation of undigested foods in the colon by its resident bacteria affects not only colonic health (protection against inflammation and tumour formation) but also influences metabolic health. Studying fermentation directly is difficult for lack of access. We hypothesise that the anatomical structure of the colon is suited to act as a fermenting chamber with the gaseous molecules (VOCs) emitted having direct effects on the colonocytes as well as gut neural and metabolic effects. We refer to this complex system as the ‘fermentome’, and further hypothesise that alteration in the ‘fermentome’ through dietary modification will have a direct impact on colonic as well as metabolic health and disease. The VOCs emitted may play a role in bacterial chemical signalling within the colon but importantly could also function as a ‘gas’ biomarker. Measurement of such VOCs through non-invasive methods would have important application as a hypothesis-generating tool with subsequent clinical application

Adipose tissue: The renaissance marked by four paradigm shifts

One of the biggest recent achievements in the study of cardio- metabolic diseases (atherosclerosis, hypertension, obesity, type 2 diabetes mellitus, metabolic syndrome, and Alzheimer`s disease, which is recently viewed as type 3 diabetes, see below) is associated with the `rediscovery` of a neglected tissue, the adipose tissue. Here we will Dance Round four paradigm shifts in the study of adipose tissue.In 1962, Thomas S. Kuhn published his book The Structure of Scientific Revolutions (1st edition, University of Chicago Press, Chicago, USA). Its publication was a landmark event in the history and philosophy of scientific knowledge (epistemology). Kuhn challenged the prevailing view of `normal science` which DANCE ROUND We dance round in a ring and suppose, But the Secret sits in the middle and knows.Robert Frost was viewed as `development-by-accumulation` of accepted facts and concepts leading - most often - to epistemological paralysis, we dubbed it neophobia (the term also used for children above the age of 1 year). Kuhn argued for a model in which a period of such conceptual continuity in normal science were interrupted by a period of revolutionary science leading to a new paradigm, an event he designated paradigm shift.At epistemological level, the adipose tissue has undergone four major paradigm shifts in last 20 years, which `upregulated` it above the horizon. Consequently, adipose tissue takes center stage in so many diseases that it leaves most scientists and medical doctors astonished

Regulation of 3β-Hydroxysteroid Dehydrogenase/∆5-∆4 Isomerase: A Review

This review focuses on the expression and regulation of 3β-hydroxysteroi ddehydrogenase/Δ5-Δ4 isomerase (3β-HSD), with emphasis on the porcine version. 3β-HSD is often associated with steroidogenesis, but its function in the metabolism of both steroids and xenobiotics is more obscure. Based on currently available literature covering humans,rodents and pigs, this review provides an overview of the present knowledge concerning the regulatory mechanisms for 3β-HSD at all omic levels. The HSD isoenzymes are essential in steroid hormone metabolism, both in the synthesis and degradation of steroids. They display tissue-specific expression and factors influencing their activity, which therefore indicates their tissue-specific responses. 3β-HSD is involved in the synthesis of a number of natural steroid hormones, including progesterone and testosterone, and the hepatic degradation of the pheromone androstenone. In general, a number of signaling and regulatory pathways have been demonstrated to influence 3β-HSD transcription and activity, e.g., JAK-STAT, LH/hCG, ERα, AR, SF-1 and PPARα. The expression and enzymic activity of 3β-HSD are also influenced by external factors, such as dietary composition. Much of the research conducted on porcine 3β-HSD is motivated by its importance for the occurrence of the boar taint phenomenon that results from high concentrations of steroids such as androstenone. This topic is also examined in this review

Grape skin improves antioxidant capacity in rats fed a high fat diet

This study was conducted to investigate the effect of dietary grape skin on lipid peroxidation and antioxidant defense system in rats fed high fat diet. The Sprague-Dawley rats were fed either control (5% fat) diet or high fat (25% fat) diet which was based on AIN-93 diet for 2 weeks, and then they were grouped as control group (C), control + 5% grape skin group (CS), high-fat group (HF), high fat + 5% grape skin group (HFS) with 10 rats each and fed corresponding diets for 4 weeks. The hepatic thiobarbituric acid reacting substances (TBARS) were increased in high fat group as compared with control group, but reduced by grape skin. The serum total antioxidant status, and activities of hepatic catalase and superoxide dismutase, xanthine oxidase and glucose-6-phosphatase were increased by supplementation of grape skin. Glutathione peroxidase activity was significantly higher in CS group than in C group. Grape skin feeding tended to increase the concentration of total glutathione, especially in control group. The ratio of reduced glutathione to oxidized glutathione was lower in high fat groups than in control groups. The ratio was increased by dietary supplementation of grape skin in control group. These results suggest that dietary supplementation of grape skin would be effective on protection of oxidative damage by lipid peroxidation through improvement of antioxidant defense system in rats fed high fat diet as well as rats with low fat diet

Neuroprotection by leptin in a rat model of permanent cerebral ischemia: effects on STAT3 phosphorylation in discrete cells of the brain

In addition to its effects in the hypothalamus to control body weight, leptin is involved in the regulation of neuronal function, development and survival. Recent findings have highlighted the neuroprotective effects of leptin against ischemic brain injury; however, to date, little is known about the role performed by the signal transducer and activator of transcription (STAT)-3, a major mediator of leptin receptor transduction pathway in the brain, in the beneficial effects of the hormone. Our data demonstrate that systemic acute administration of leptin produces neuroprotection in rats subjected to permanent middle cerebral artery occlusion (MCAo), as revealed by a significant reduction of the brain infarct volume and neurological deficit up to 7 days after the induction of ischemia. By combining a subcellular fractionation approach with immunohistofluorescence, we observe that neuroprotection is associated with a cell type-specific modulation of STAT3 phosphorylation in the ischemic cortex. The early enhancement of nuclear phospho-STAT3 induced by leptin in the astrocytes of the ischemic penumbra may contribute to a beneficial effect of these cells on the evolution of tissue damage. In addition, the elevation of phospho-STAT3 induced by leptin in the neurons after 24 h MCAo is associated with an increased expression of tissue inhibitor of matrix metalloproteinases-1 in the cortex, suggesting its possible involvement to the neuroprotection produced by the adipokine

Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics

BACKGROUND: Recently, it has been shown that increasing body mass index (BMI) in asthma is associated with reduced exhaled NO. Our objective in this study was to determine if the BMI-related changes in exhaled NO differ across asthmatics and controls, and to determine if these changes are related to increased airway oxidative stress and systemic levels of leptin and adiponectin. METHODS: Observational study of the association of BMI, leptin, and adiponectin with exhaled nitric oxide (NO) and exhaled 8-isoprostanes in 67 non-smoking patients with moderate to severe persistent asthma during baseline conditions and 47 controls. Measurements included plasma levels of leptin, adiponectin, exhaled breath condensates for 8-isoprostanes, exhaled NO, pulmonary function tests, and questionnaires regarding asthma severity and control. RESULTS: In asthmatics, BMI and the ratio of leptin to adiponectin were respectively associated with reduced levels of exhaled NO (β = -0.04 [95% C.I. -0.07, -0.1], p < 0.003) and (β = -0.0018 [95% C.I. -0.003, -0.00034], p = 0.01) after adjusting for confounders. Also, BMI was associated with increased levels of exhaled 8-isoprostanes (β = 0.30 [95% C.I. 0.003, 0.6], p = 0.03) after adjusting for confounders. In contrast, we did not observe these associations in the control group of healthy non-asthmatics with a similar weight distribution. CONCLUSION: In adults with stable moderate to severe persistent asthma, but not in controls, BMI and the plasma ratio of leptin/adiponectin is associated with reduced exhaled NO. Also, BMI is associated with increased exhaled 8-isoprostanes. These results suggest that BMI in asthmatics may increase airway oxidative stress and could explain the BMI-related reductions in exhaled NO