ASSOCIATION OF GHRELIN RECEPTOR AND INFLAMMATION IN PERI-ATRIAL ADIPOSE TISSUE FROM OBESE PATIENTS WITH POSTOPERATIVE ATRIAL FIBRILLATION.

CONTEXT: Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. The increasing evidence supports links between inflammation and AF. There is evidence showing that obesity is a major cause of adipose tissue (AT) inflammation. Ghrelin (GHRL), through its growth hormone secretagogue receptor (GHS-R) present on adipose tissue macrophages (ATMs), could modulate AT inflammation. OBJECTIVE: Our study aimed to evaluate the role of adipose tissue macrophages (ATMs) and their GHS-R in adipose tissue samples of right atrial appendages (RAA) biopsies. SUBJECTS AND METHOD: We obtained RAA biopsies from 10 obese patients, undergoing cardiac surgery for coronary artery bypass graft (CABG) and developing postoperative atrial fibrillation (POAF). The epicardial tissue samples were examined using immunohistochemistry to visualize and quantify CD68 and GSH-R expression of the ATMs. RESULTS: Histologically, the mean adipocyte diameter (MAD) of epicardial adipose tissue (EAT) was larger in EAT samples with inflammation as compared to EAT without inflammation (84.2 µm vs. 79.6 µm). The expression of CD68 was lower in EAT without inflammation as compared to EAT with inflammation in adipose tissue samples. Similarly, the expression of GSH-R was lower in EAT samples without inflammation as compared to EAT samples with inflammation in adipose tissue. CONCLUSIONS: Increased epicardial fat area, macrophage infiltration, and GHS-R expression in epicardial ATMs appeared to be associated with postoperative atrial fibrillation in obese patients.

VITAMIN D AND TISSULAR EXPRESSION OF VITAMIN D RECEPTOR IN OBESITY.

Vitamin D (VitD), a lipid-soluble hormone, is able to regulate the transcription of many genes through vitamin D receptor (vitD receptor-VDR). It has been shown that VitD deficiency is associated with obesity, characterized by a low degree inflammatory state, which contribute to the pathogeny of metabolic syndrome and type 2 diabetes mellitus. VitD deficiency is a public health problem, at the same time the global prevalence of obesity and cardiovascular diseases is continuously growing. Evidence from recent studies on animal models suggest that VitD or VDR deficiency promotes cardiomyocyte hypertrophy, which can be one of the mechanisms for increasing cardiovascular risk. The heart is one of the target organs of action for VitD, because VDR is expressed in cardiomyocytes. Also, previous in vitro studies have shown that VitD is able to inhibit the production of monocyte chemotactic factors (MCP-1) and other pro-inflammatory mediators in human preadipocytes and mature adipocytes. Inflammation is an important factor in the pathogenesis of atherosclerosis. In obesity there are not known data about correlations between plasma levels of VitD and VDR expression in the subcutaneous fat tissue, epicardial visceral adipose tissue, and in particular in myocardium. Also, there are still no studies to test VDR expression in myocardial cells and to investigate the results of dietary VitD supplementation on the expression of VDR in the epicardial adipose tissue and myocardium.

Current status in vitamin D and regulatory T cells--immunological implications.

There has been a continuous effort to understand possible non-Ca metabolism roles of vitamin D, including its role in the immune system and, in particular, in T cell-medicated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations, when we refer to immune system, and pretty much in any human tissue and cells. Until the eighties, no one had imagined that vitamin D might play a role in the functioning of the immune system. Today we accepted that the normal immune system harbors a regulatory T cell (Treg) population specialized for immune suppression. Currently, the most commonly known regulatory T-cell lineage is called CD4+ CD25high FoxP3+ regulatory T cells. Several autoimmune disorders have been linked to a deficiency in vitamin D3. In some autoimmune diseases, including multiple sclerosis (MS), a compromised Treg function is believed to be critically involved in the disease process. Vitamin D insufficiency has ramifications not only for bone health, but also in other non-skeletal areas of vitamin D function, such as immune cells, muscle cells and, perhaps, adipocytes. As a final conclusion, further researches in the field of vitamin D, Tregs, immunity (inflammatory processes, rejection, autoimmune diseases, etc.), either in vitro on cell cultures or in vivo using lab animals or volunteers are still necessary.

Effects of dietary flaxseed supplementation on renal oxidative stress in experimental diabetes.

UNLABELLED: Previous results demonstrate that experimental diabetes mellitus is accompanied by increased oxidant stress within glomeruli. Evidence are emerging that dietary flaxseed supplementation can have beneficial effects on oxidative stress. MATERIALS AND METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) in male Golden Syrian hamsters, and both diabetic and control groups were fed either standard diet, or standard diet supplemented with flaxseed (15 g/100 g diet), for 20 weeks. At the end of the study, blood samples and renal homogenates were used for determination of oxidative stress markers. RESULTS: STZ-induced diabetes in hamsters substantially increased malondialdehyde levels along with corresponding decrease in the antioxidants levels. Supplementation of flaxseed resulted in the decrease in serum and renal homogenate malondialdehyde levels. The activities of antioxidant enzymes, total glutathione (tGSH) and superoxiddismutase (SOD) were also concomitantly raised to near normal levels by flaxseed supplementation diabetic hamsters. CONCLUSION: Dietary flaxseed supplementation in diabetes mellitus may have beneficial effects on diabetic nephropathy evolution by reducing the levels of oxidative stress and increasing the antioxidant defense systems.

The effects of dietary flaxseed supplementation on lipid metabolism in streptozotocin-induced diabetic hamsters.

UNLABELLED: Vascular complications, such as atherosclerosis, represent an important cause of morbidity and mortality in diabetic patients. The aim of this study was to investigate the effects of dietary flaxseed supplementation, a rich source of lignans, a-linolenic acid and soluble fiber mucilage on serum and hepatic lipid concentrations in streptozotocin-induced diabetes in hamsters. METHODS: Twenty-four male Golden Syrian hamsters were used in this experiment; diabetes was induced in half of them by intraperitoneal injection of streptozotocin (50 mg/kg body weight), and both diabetic and control groups were divided in 2 subgroups, one fed standard diet, and one fed standard diet supplemented with flaxseed (15%), for 20 weeks. Serum total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides (TG), cholesterol/HDL-cholesterol ratio and hepatic cholesterol and triglycerides were measured at the end of the experiment. RESULTS: Dietary flaxseed supplementation in diabetic hamsters was associated with significant reductions in serum TC (-24.9%), TC/HDL-C ratio (-60%) and increase in serum HDL-C (+91%) as compared to diabetic group without supplementation. There were no significant differences in serum TG levels between diabetes supplemented with flaxseed and diabetic groups. Also, flaxseed supplementation in diabetes induced significant reductions in hepatic cholesterol (-39.5%) and triglycerides levels (-28.8%). CONCLUSIONS: These results suggest that dietary flaxseed supplementation may reduce the incidence of diabetic macrovascular complications through improvement of lipid profile.