Impact of glucocorticoid hormones on adipokine secretion and human adipose tissue metabolism.

The glucocorticoid hormones alter the metabolism of the adipose tissue after an approximately 2-h lag period. The effects are mediated through the nuclear receptors that alter the expression of a wide variety of genes through the mechanisms that are similar to those seen in the other cells. There are many direct metabolic effects of the glucocorticoids on the adipose tissue metabolism, and every year, new effects are added to the list of proteins whose expression is influenced by the glucocorticoids.

Exercise training does not increase muscle FNDC5 protein or mRNA expression in pigs.

Background: Exercise training elevates circulating irisin and induces the expression of the FNDC5 gene in skeletal muscles of mice. Our objective was to determine whether exercise training also increases FNDC5 protein or mRNA expression in the skeletal muscles of pigs as well as plasma irisin.

Methods: Castrated male pigs of the Rapacz familial hypercholesterolemic (FHM) strain and normal (Yucatan miniature) pigs were sacrificed after 16-20 weeks of exercise training.

Adult epicardial fat exhibits beige features.

Context: Human epicardial fat has been designated previously as brown-like fat. The supraclavicular fat depot in man has been defined as beige coexistent with classical brown based on its gene expression profile.

Objective: The aim of the study was to establish the gene expression profile and morphology of human epicardial and visceral paracardial fat compared with sc fat.

Human epicardial fat: what is new and what is missing?

1. Putative physiological functions of human epicardial adipose tissue (EAT) include: (i) lipid storage for the energy needs of the myocardium; (ii) thermoregulation, whereby brown fat components of EAT generate heat by non-shivering thermogenesis in response to core cooling; (iii) neuroprotection of the cardiac autonomic ganglia and nerves; and (iv) regulation of vasomotion and luminal size of the coronary arteries. Under pathophysiological circumstances, EAT may play an adverse paracrine role in cardiac arrhythmias and in lipotoxic cardiomyopathy, but of major current interest is its hypothetical role as an immunological organ contributing to inflammation around coronary artery disease (CAD).

Depot-specific overexpression of proinflammatory, redox, endothelial cell, and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis.

Background: Pro- and antiinflammatory genes are expressed in epicardial adipose tissue (EAT). Our objectives were to characterize genes in EAT that may contribute specifically to coronary atherogenesis and to measure circulating adipokines matched to their messenger RNAs (mRNAs) in EAT. We hypothesized that severe coronary atherosclerosis (CAD) would preferentially affect gene expression in EAT as compared to substernal fat or subcutaneous thoracic adipose tissue (SAT), as well as circulating levels of adipokines.

Adipose tissue-derived soluble fms-like tyrosine kinase 1 is an obesity-relevant endogenous paracrine adipokine.

Adipose tissue growth depends on angiogenesis. We tested the hypothesis that adipose tissue produces factors relevant to angiogenesis. We obtained fat biopsies in 2 different patient cohorts, cultured adipose-derived stem cells and studied mature adipocytes.

Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: changes associated with pioglitazone.

Objective: To determine changes in gene expression in epicardial adipose tissue (EAT) associated with coronary atherosclerosis (CAD) and effects of pioglitazone therapy.

Research Design And Methods: Genes were quantified by RT-PCR in EAT and thoracic subcutaneous adipose tissue (SAT) obtained during surgery in CAD patients with metabolic syndrome (MS) or type 2 diabetes and control subjects with minimal or no CAD and no MS or type 2 diabetes.

Results: Increased expression of interleukin-1 receptor antagonist (IL-1Ra) and IL-10, a trend for higher IL-1β, and no change in peroxisome proliferator-activated receptor-γ (PPARγ) was found in EAT from MS or type 2 diabetes.

Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat.

Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD.

Release of inflammatory mediators by human adipose tissue is enhanced in obesity and primarily by the nonfat cells: a review.

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGFbeta1, TNFalpha, IL-1beta, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue.

The inflammatory response seen when human omental adipose tissue explants are incubated in primary culture is not dependent upon albumin and is primarily in the nonfat cells.

Background: The present studies were designed to investigate the changes in gene expression during in vitro incubation of human visceral omental adipose tissue explants as well as fat cells and nonfat cells derived from omental fat.

Methods: Adipose tissue was obtained from extremely obese women undergoing bariatric surgery. Explants of the tissue as well as fat cells and the nonfat cells derived by digestion with collagenase were incubated for 20 minutes to 48 h.

Human epicardial adipokine messenger RNAs: comparisons of their expression in substernal, subcutaneous, and omental fat.

We compared the gene expression of inflammatory and other proteins by real-time quantitative polymerase chain reaction in epicardial, substernal (mediastinal) and subcutaneous sternal, upper abdominal, and leg fat from coronary bypass patients and omental (visceral) fat from extremely obese women undergoing bariatric surgery. We hypothesized that (1) epicardial fat would exhibit higher expression of inflammatory messenger RNAs (mRNAs) than substernal and subcutaneous fat and (2) epicardial mRNAs would be similar to those in omental fat. Epicardial fat was clearly different from substernal fat because there was a far higher expression of haptoglobin, prostaglandin D(2) synthase, nerve growth factor beta, the soluble vascular endothelial growth factor receptor (FLT1), and alpha1 glycoprotein but not of inflammatory adipokines such as monocyte chemoattractant protein-1, interleukin (IL)-8, IL-1beta, tumor necrosis factor alpha, serum amyloid A, plasminogen activator inhibitor-1, or adiponectin despite underlying coronary atherosclerosis.

Dexamethasone and the inflammatory response in explants of human omental adipose tissue.

Dexamethasone is a synthetic glucocorticoid that is a potent anti-inflammatory agent. The present studies examined the changes in gene expression of 64 proteins in human omental adipose tissue explants incubated for 48h both in the absence and presence of dexamethasone as well as the release of 8 of these proteins that are putative adipokines. The proteins were chosen because they are inflammatory response proteins in other cells, are key regulatory proteins or are proteins with known functions.

Release of 12 adipokines by adipose tissue, nonfat cells, and fat cells from obese women.

The relative release in vitro of endothelin-1, zinc-alpha2-glycoprotein (ZAG), lipocalin-2, CD14, RANTES (regulated on activation, normal T cell expressed and secreted protein), lipoprotein lipase (LPL), osteoprotegerin (OPG), fatty acid-binding protein 4 (FABP-4), visfatin/PBEF/Nampt, glutathione peroxidase-3 (GPX-3), intracellular cell adhesion molecule 1 (ICAM-1), and amyloid A was examined using explants of human adipose tissue as well as the nonfat cell fractions and adipocytes from obese women. Over a 48-h incubation the majority of the release of LPL was by fat cells whereas that of lipocalin-2, RANTES, and ICAM-1 was by the nonfat cells present in human adipose tissue. In contrast appreciable amounts of OPG, amyloid A, ZAG, FABP-4, GPX-3, CD14, and visfatin/PBEF/Nampt were released by both fat cells and nonfat cells.

Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat.

Context: Uncoupling protein-1 (UCP-1) is the inner mitochondrial membrane protein that is a specific marker for and mediator of nonshivering thermogenesis in brown adipocytes.

Objective: This study was performed to better understand the putative thermogenic function of human epicardial fat.

Design: We measured the expression of UCP-1 and brown adipocyte differentiation transcription factors PR-domain-missing 16 (PRDM16) and peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) in epicardial, substernal, and sc thoracic, abdominal, and leg fat.

Stimulation of human omental adipose tissue lipolysis by growth hormone plus dexamethasone.

Growth hormone [GH] administration results in a reduction in adiposity of humans that is attributed to stimulation of lipolysis. We examined the effect of direct addition of human GH, in both the absence and presence of dexamethasone [Dex], as well as that of interferon beta on lipolysis by omental adipose tissue explants from obese women incubated for 48h in primary culture. There was a significant stimulation of lipolysis by GH in the presence of Dex but not by Dex or GH alone.

Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue.

The messenger RNA (mRNA) distribution of 60 proteins was examined in the 3 fractions obtained by collagenase digestion (fat cells and the nonfat cells comprising the tissue remaining after collagenase digestion [matrix] and the stromovascular cells) of omental adipose tissue obtained from morbidly obese women undergoing bariatric surgery. Fat cells were enriched by at least 3-fold as compared with nonfat cells in the mRNAs for retinol binding protein 4, angiotensinogen, adipsin, glutathione peroxidase 3, uncoupling protein 2, peroxisome proliferator-activated receptor gamma, cell death-inducing DFFA-like effector A, fat-specific protein 27, 11beta-hydroxysteroid dehydrogenase 1, glycerol channel aquaporin 7, NADPH:quinone oxidoreductase 1, cyclic adenosine monophosphate phosphodiesterase 3B, glyceraldehyde-3-phosphate dehydrogenase, insulin receptor, and amyloid A1. Fat cells were also enriched by at least 26-fold in the mRNAs for proteins involved in lipolysis such as hormone-sensitive lipase, lipoprotein lipase, adipose tissue triglyceride lipase, and FAT/CD36.

Release in vitro of adipsin, vascular cell adhesion molecule 1, angiotensin 1-converting enzyme, and soluble tumor necrosis factor receptor 2 by human omental adipose tissue as well as by the nonfat cells and adipocytes.

The relative release in vitro of adipsin, vascular cell adhesion molecule (VCAM) 1, angiotensin 1-converting enzyme (ACE), and soluble tumor necrosis factor alpha receptor 2 (sTNFR2) by explants of human omental and subcutaneous adipose tissue as well as the nonfat cell fractions and adipocytes from morbidly obese gastric bypass women was compared with that by tissue from obese abdominoplasty patients. Release of VCAM-1 and ACE by omental adipose tissue explants was 220% and 80% greater, respectively, over 48 hours of incubation than that by subcutaneous adipose tissue explants. However, this difference was not seen when release by adipocytes derived from omental fat was compared with that by adipocytes from subcutaneous fat.

Site -2548 of the leptin gene is associated with gender-specific trends in newborn size and cord leptin levels.

Objective: Circulating leptin levels positively correlate with adult BMI and size at birth. Previous studies found gender-specific associations between polymorphisms in the leptin gene and postnatal obesity-related traits or circulating leptin levels. We examined the relationships among leptin gene polymorphisms, size for gestational age, umbilical cord leptin, and gender.

Association between paternally inherited haplotypes upstream of the insulin gene and umbilical cord IGF-II levels.

The insulin (INS) and IGF 2 (IGF2) genes are in close proximity to each other and undergo maternal imprinting during fetal growth. We investigated the association between maternal and umbilical cord IGF 2 protein (IGF-II) levels and single nucleotide polymorphisms (SNPs) in the INS and IGF2 genes in 207 healthy African-American mother-newborn pairs. No association was found between maternal IGF-II levels and polymorphism in the INS-IGF2 locus.

Are African-Americans as successful as Caucasians after laparoscopic gastric bypass?

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) has been demonstrated to provide weight loss comparable to open gastric bypass. It has been suggested that African-Americans (AA) are not as successful as Caucasians (CA) after bariatric surgery. Our hypothesis was that AAs are just as successful as CA after LRYGBP in terms of weight loss and comorbidity improvement.

Human epicardial adipose tissue: a review.

We discuss the anatomy, physiology, and pathophysiology of epicardial adipose tissue and its relationship to coronary atherosclerosis. Epicardial fat stores triglyceride to supply free fatty acids for myocardial energy production and produces adipokines. It shares a common embryological origin with mesenteric and omental fat.

Laparoscopic bariatric patients' will to help: the foundation of research.

Background: Bariatric surgery is a fast growing field. Clinical research is essential to its safe delivery. Bariatric patient enthusiasm for research participation has never been objectively measured.

Comparison of IL-8, IL-6 and PGE(2) formation by visceral (omental) adipose tissue of obese Caucasian compared to African-American women.

Background: One of the key consequences of obesity is an enhanced release of cytokines such as IL-8 and IL-6 by adipose tissue. There may be differences in adiposity, inflammatory markers, and medical co-morbidity between morbidly obese African-American (AA) and Caucasian (CA) women. We hypothesized that there are ethnic differences in inflammatory markers and medical co-morbidities.

Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells.

The white adipose tissue, especially of humans, is now recognized as the central player in the mild inflammatory state that is characteristic of obesity. The question is how the increased accumulation of lipid seen in obesity causes an inflammatory state and how this is linked to the hypertension and type 2 diabetes that accompanies obesity. Once it was thought that adipose tissue was primarily a reservoir for excess calories that were stored in the adipocytes as triacylglycerols.