Targeting the organ-specific adiposity.

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Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or “adipokines” have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of “cross talk” between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals

Pericardial Adipose Tissue, Atherosclerosis, and Cardiovascular Disease Risk Factors: The Jackson Heart Study Comment on Liu et al.

We read the article by Liu et al. (1) with great interest. The investigators carefully stated that because it is difficult to distinguish pericardial from epicardial fat with computed tomography (CT), they measured pericardial adipose tissue by the combination of pericardial fat and epicardial fat. While they recognized this important misclassification, we also noted that they not only technically but conceptually discussed pericardial and epicardial fat as identical to adipose tissue. This appears to be incorrect and misleading. Epicardial and pericardial adipose tissue are clearly different anatomically, embriologically, physiologically, biomolecularly, and clinically (2,3). Epicardial adipose tissue is the fat located between

Editorial Disease of Adrenal Glands

International audienceThe adrenal gland has been historically an object of interest and scientific curiosity. This is also due to its very heterogeneous structure, number of hormones, complex neural innervation, and multiple and different physiological functions. The adrenal gland also entails an outstanding example of paracrine interactions occurring between histogenetically different tissues as the cortex and the medulla. This special issue is a great opportunity for the reader to learn the latest and emerging findings on the pathophysiol-ogy, diagnosis, and treatment of the adrenal glands disorders. The issue provides a variety of excellent articles covering a broad and contemporary spectrum of aspects of the diseases of the adrenal gland. Of particular interest and novelty is the interplay between hormones of the adrenal glands and other organs, such as the adipose tissue, the endothelium, the bone, and even the brain. In addition to the well-established effects on lipid and glucose metabolism, the hormones of the adrenal glands display a fascinating cross talk with the adipose tissue [1– 3]. The interaction between the adrenals and adipokines is extensively discussed by A. Y. Kargi and G. Iacobellis in a comprehensive and updated review paper. The potential of the fat depot surrounding the adrenal tumors to act like a brown adipose tissue (BAT) is a rapidly emerging topic that will certainly deserve further attention and investigation [4]. Interestingly the authors provided a theoretical basis for potential future pharmacological interventions aimed at adrenal hormone targets in the adipose tissue. Primary aldosteronism is the most common endocrine cause of arterial hypertension. It can cause excess damage to the organs that are target of hypertension and higher cardiometabolic risk [5]. This contention was supported by previous experimental data obtained by Karl Weber's group in rats infused with aldosterone, which exhibited hypercalciuria and raised parathyroid hormone (PTH) levels [6], and, more importantly, by findings in patients with aldosterone-producing adenoma who also showed elevated serum PTH levels that were then normalized by adrenalectomy [7]. The effect of the adrenal hormones on bone metabolism in patients with primary aldosteronism is nicely addressed by L. Petramala et al. The authors sought to test the hypothesis that hyperaldosteronism may influence mineral homeostasis through higher urinary calcium excretion leading eventually to secondary hyperparathyroidism. Of further interest, G. Mazzocchi et al. showed that PTH stimulates aldosterone secretion in a concentration-dependent manner [8], a finding that was complemented by the demonstration of the miner-alocorticoid receptor in the human parathyroid cells [9]. It is well established that a substantial amount of sodium is bound to proteoglycans of bone, connective tissue, and cartilage and that the osmotic force created by the high sodium concentration maintains the high water content in the latter tissue, allowing it to withstand high pressures during exercise [10]. In this special issue P. Alonso et al. further expand on the relationships between the adrenal gland and the skeleton by showing a reduction in the bone mineral densit

Echocardiographic Assessment of Epicardial Adipose Tissue - A Marker of Visceral Adiposity

Visceral adipose tissue predicts an unfavorable cardiovascular and metabolic risk profile in humans. Existing methods to assess visceral adipose tissue have been limited. Thus, echocardiographic assessment of epicardial adipose tissue as a marker of visceral adiposity was suggested. The technique has been shown to be a very reliable method and an excellent measure of visceral adiposity. In this article, epicardial adipose tissue’s localization on the heart, function, method of assessment and reliability as a marker of visceral adiposity is briefly reviewed. Areas of the technique requiring further study are identified

Relation of epicardial fat and alanine aminotransferase in subjects with increased visceral fat

Background: Increased visceral adipose tissue (VAT) is a risk factor for an unfavorable cardio-metabolic profile and fatty liver. Individuals with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART) can be associated with metabolic syndrome (MS) and higher visceral fat. However, the potential link between cardiac adiposity, emerging index of visceral adiposity, and fatty liver is still unexplored. Objective: To evaluate whether echocardiographic epicardial adipose tissue, index of cardiac adiposity, could be related to serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, surrogate markers of fatty liver, in HIV-infected patients with (HIV+MS+) and without HAART-associated MS (HIV+MS-). Methods and Procedures: This was a cross-sectional observational study on 57 HIV+MS+ patients, 52 HIV+MS- and 57 HIV-negative subjects with MS (HIV-MS+), as control group. Epicardial fat thickness and intra-abdominal VAT were obtained by echocardiography and magnetic resonance imaging (MRI), respectively. Serum ALT and AST activity, plasma adiponectin levels, and MS biochemical parameters were measured. Results: Echocardiographic epicardial fat thickness was correlated with MRI-VAT (r = 0.83, P < 0.01), AST/ALT ratio (r = 0.77, P < 0.01), ALT (r = 0.58, P < 0.01), AST (r = 0.56, P < 0.01), and adiponectin (r = -0.45, P < 0.01) in HIV+MS+. MRI-VAT and AST/ALT ratio were the best correlates of epicardial fat thickness (r(2) = 0.45, P < 0.01). Discussion: This study shows for the first time a clear relationship of epicardial fat, index of cardiac and visceral adiposity, and serum ALT and AST activity, markers of fatty liver, in subjects with increased visceral adiposity and cardio-metabolic risk. This correlation seems to be independent of overall adiposity and rather function of excess visceral adiposity

Brown Fat Expresses Adiponectin in Humans

The presence of brown adipose tissue (BAT) in humans is unclear. Pheochromocytomas (PHEO) are rare tumors of neuroectodermal origin which occur in 0.1-0.2% of patients with hypertension. We sought to evaluate the presence and activity of BAT surrounding adrenal PHEO in a well-studied sample of 11 patients who were diagnosed with PHEO and then underwent adrenalectomy. Areas of white fat (WAT) and BAT surrounding PHEO were obtained by Laser Capture Microdissection for analysis of uncoupling protein (UCP)-1 and adiponectin mRNA expression. Adiponectin and UCP-1 mRNA levels were significantly higher in BAT than in WAT (0.62 versus 0.15 and 362.4 versus 22.1, resp., for both). Adiponectin mRNA levels significantly correlated with urinary metanephrines (, ), vanilly mandelic acid (VMA) (, ), and serum adiponectin levels (, ). Serum adiponectin levels significantly decreased ( μg/mL versus  μg/mL, ) after adrenalectomy in PHEO subjects. This study provides the following findings: (1) BAT surrounding PHEO expresses adiponectin and UCP-1 mRNA, (2) expression of adiponectin mRNA is significantly higher in BAT than in WAT surrounding PHEO, and (3) catecholamines and serum adiponectin levels significantly correlate with BAT UCP-1 and adiponectin mRNA

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology

Bakground &amp; aims Although discrimination of the model for end stage liver disease (MELD) is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discrimination and calibration performance of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intra-hepatic portosystemic shunt (TIPS); classic MELD-Mayo; MELD-UNOS, used by United Network for Organ Sharing (UNOS). Recalibration and model updating were also explored. Methods 776 patients submitted to elective TIPS (TIPS cohort), and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. Results Major patient characteristics in TIPS/non-TIPS cohorts were: viral etiology 402/188, alcoholic 185/130, NASH 65/33; mean follow-up± SD 25±9/19±21months; 3-6-12 month mortality were respectively, 57-102-142/31-47-99. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post-hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used for a MELD updating. Conclusions In this validation study the MELD performance was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for a MELD updating are proposed. Lay summary While discrimination performance of the Model for End Stage Liver Disease (MELD) is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in two independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis and propose a validated model recalibration. Candidate variables for a MELD updating are proposed

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation