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Commensal and pathogenic bacteria hydrolyze host lipid substrates with secreted lipases and phospholipases for nutrient acquisition, colonization, and infection. Bacterial lipase activity on mammalian lipids and phospholipids can promote release of free fatty acids from lipid stores, detoxify antimicrobial lipids, and facilitate membrane dissolution. The gram-positive bacterium Staphylococcus aureus secretes at least two lipases, Sal1 and glycerol ester hydrolase (Geh), with specificities for short- and long-chain fatty acids, respectively, each with roles in the hydrolysis of environmental lipids. In a recent study from our group, we made the unexpected observation that Geh released by S. aureus inhibits activation of innate immune cells. Herein, we investigated the possibility that S. aureus lipases interface with the host immune system to blunt innate immune recognition of the microbe. We found that the Geh lipase, but not other S. aureus lipases, prevents activation of innate cells in culture. Mutation of geh leads to enhancement of proinflammatory cytokine production during infection, increased innate immune activity, and improved clearance of the bacterium in infected tissue. These in vitro and in vivo effects on innate immunity were not due to direct functions of the lipase on mammalian cells, but rather a result of inactivation of S. aureus lipoproteins, a major pathogen-associated molecular pattern (PAMP) of extracellular gram-positive bacteria, via ester hydrolysis. Altogether, these studies provide insight into an adaptive trait that masks microbial recognition by innate immune cells through targeted inactivation of a broadly conserved PAMP. [ABSTRACT FROM AUTHOR]

Lipid digestion is an interfacial process that is largely controlled by the adsorption of lipase + colipase + bile salts onto the surface of the emulsified lipid droplets. Therefore, engineering oil-in-water (O/W) interfaces that prevent competitive displacement by bile salts and/or delay the transportation of lipase to the hydrophobic lipid core can be effective strategies to delay lipolysis. In this study, we present such an interface using composite protein-particle system, consisting of whey protein isolate (WPI) (1 wt%) + cellulose nanocrystals (CNCs) (1–3 wt%). Droplet size, microscopy at various length scales (confocal, electron microscopy), ζ -potential and kinetics of fatty acid release were used to assess how the presence of CNCs impacted the microstructural stability of the emulsions in in vitro duodenal conditions (pH 6.8, 37 ○ C). Adding CNCs at sufficiently high concentrations (3 wt%) significantly decreased the rate and degree of lipolysis as compared to that of protein-coated emulsion droplets. The principal cause of this altered lipolysis profile was the binding of bile salts by CNCs, which restricted both the interfacial displacement and solubilisation of lipid-digestion products by bile salts. The CNCs can be envisaged to be strongly bound to the protein-coated droplets by virtue of hydrogen bonding with the underlying protein. Furthermore, the ability of the CNCs in the continuous phase to bridge several protein-coated droplets reduced the overall surface area available for the lipolysis. Composite WPI + CNC interface holds promise in designing physiologically relevant emulsions to target satiety or delivery systems for sustained release of lipophilic components. [ABSTRACT FROM AUTHOR]

This study aimed to determine the influence of cyclic guanosine 3’5’-monophosphate (cGMP) and cGMP-dependent kinase (PKG) during in vitro maturation (IVM) on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs), and on embryo development and cryosurvival. COCs were matured with cGMP/PKG modulators and assessed for metaphase II rates (MII), cGMP levels, lipid content in oocytes (OO), transcript abundance for genes involved in lipolysis (ATGL) and lipid droplets (PLIN2) in cumulus cells (CC) and OO, and presence of phosphorylated (active) hormone sensitive lipase (HSLser563) in OO. Embryo development, lipid contents and survival to vitrification were also assessed. Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme) with 10-5M sildenafil (SDF) during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in untreated controls, p<0.05) and did not affect on maturation rate (84.3±6.4% MII). Fetal calf serum (FCS) in IVM medium decreased cGMP in COCs compared to bovine serum albumin (BSA) + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05). FCS increased lipid content in OO (40.1 FI, p<0.05) compared to BSA (34.6 FI), while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05). PKG inhibitor (KT5823) reversed this effect (38.9 FI, p<0.05). ATGL and PLIN2 transcripts were detected in CC and OO, but were affected by cGMP and PKG only in CC. HSLser563 was detected in OO matured with or without modulators. Reduced lipid content in embryos were observed only when SDF was added during IVM and IVC (27.6 FI) compared to its use in either or none of the culture periods (34.2 FI, p<0.05). Survival to vitrification was unaffected by SDF. In conclusion, cGMP and PKG are involved in lipolysis in OO and possibly in CC and embryos; serum negatively affects this pathway, contributing to lipid accumulation, and cGMP modulation may reduce lipid contents in oocytes and embryos, but without improving embryo cryotolerance. [ABSTRACT FROM AUTHOR]

Hypothesis Bile micelles are thought to mediate intestinal absorption, in part by providing a phase into which compounds can partition. Solubilizing capacity of bile micelles is enhanced during the digestion of fat rich food. We hypothesized that the intestinal digestion of triglycerides causes an increase in volume of micelles that can be quantitatively monitored over the course of digestion using small-angle neutron scattering (SANS), and that SANS can enable evaluation of the contribution of each of the components present during digestion to the size of micelles. Experiments SANS was used to characterize the size and shape of micelles present prior to and during the in vitro simulated intestinal digestion of a model food-associated lipid, triolein. Findings Pre-lipolysis mixtures of a bile salt and phospholipid simulating bile concentrations in fed conditions were organized in micelles with an average volume of 40 nm 3 . During lipolysis, the micelle volume increased 2.5-fold over a 2-h digestion period due to growth in one direction as a result of insertion of monoglycerides and fatty acids. These efforts represent a basis for quantitative mechanistic understanding of changes in solubilizing capacity of the intestinal milieu upon ingestion of a fat-rich meal. [ABSTRACT FROM AUTHOR]

On the basis of studies that investigated the intraportal versus systemic insulin infusion and transendothelial transport of insulin, we proposed the "single gateway hypothesis," which supposes an indirect regulation of hepatic glucose production by insulin; the rate-limiting transport of insulin across the adipose tissue capillaries is responsible for the slow suppression of free fatty acids (FFAs), which in turn is responsible for delayed suppression of hepatic endogenous glucose production (EGP) during insulin infusion. Preventing the fall in plasma FFAs during insulin infusion either by administering intralipids or by inhibiting adipose tissue lipolysis led to failure in EGP suppression, thus supporting our hypothesis. More recently, mice lacking hepatic Foxo1 in addition to Akt1 and Akt2 (L-AktFoxo1TKO), all required for insulin signaling, surprisingly showed normal glycemia. Inhibiting the fall of plasma FFAs in these mice prevented the suppression of EGP during a clamp, reaffirming that the site of insulin action to control EGP is extrahepatic. Measuring whole-body turnover rates of glucose and FFAs in L-AktFoxo1TKO mice also confirmed that hepatic EGP was regulated by insulin-mediated control of FFAs. The knockout mouse model in combination with sophisticated molecular techniques confirmed our physiological findings and the single gateway hypothesis. [ABSTRACT FROM AUTHOR]

We recently demonstrated that short-term estradiol (E2) treatment improved insulin-mediated suppression of lipolysis in postmenopausal women, but to a greater extent in those who were late compared to early postmenopausal. In this follow-up study we tested whether subcutaneous adipose tissue (SAT) expression of estrogen receptors (ER) α and β differs between early and late postmenopausal women. We further tested whether the balance of ERα to ERβ in SAT determined the effect of E2 on SAT insulin sensitivity. The present study included 35 women who were ≤6 years past menopause (EPM; n = 16) or ≥10 years past menopause (LPM; n = 19). Fasted SAT samples were taken following 1-week transdermal E2 treatment or placebo (PL) in a random cross-over design. Samples were analyzed for nuclear/cytosolic protein content and mRNA expression using Western blot and qPCR, respectively. While ESR1 increased slightly (~1.4-fold) following E2 treatment in both groups, ERα and ERβ protein expression did not differ between groups at baseline or in response to E2. However, the balance of ERα/ERβ protein in the SAT nuclear fraction increased 10% in EPM compared to a 25% decrease in LPM women (group x treatment interaction, p<0.05). A greater proportion of ERα/ERβ protein in the nuclear fraction of SAT at baseline (placebo day) was associated with greater reduction in SAT insulin resistance (i.e., better suppression of lipolysis, EC50) in response to E2 (r = -0.431, p<0.05). In conclusion, there do not appear to be differences in the proportion of adipose tissue ERα/ERβ protein in late, compared to early, postmenopausal women. However, the balance of ERα/ERβ may be important for E2-mediated improvement in adipose tissue insulin sensitivity. Trial Registration: Clinical Trials#: [ABSTRACT FROM AUTHOR]

5'-AMP-activated protein kinase (AMPK) is activated as a consequence of lipolysis and has been shown to play a role in regulation of adipose tissue mitochondrial content. Conversely, the inhibition of lipolysis has been reported to potentiate the induction of protein kinase A (PKA)-targeted genes involved in the regulation of oxidative metabolism. The purpose of the current study was to address these apparent discrepancies and to more fully examine the relationship between lipolysis, AMPK, and the β-adrenergic-mediated regulation of gene expression. In 3T3-L1 adipocytes, the adipose tissue triglyceride lipase (ATGL) inhibitor AT-GListatin attenuated the Thr172 phosphorylation of AMPK by a β3-adrenergic agonist (CL 316,243) independent of changes in PKA signaling. Similarly, CL 316,243-induced increases in the Thr172 phosphorylation of AMPK were reduced in adipose tissue from whole body ATGL-deficient mice. Despite reductions in the activation of AMPK, the induction of PKA-targeted genes was intact or, in some cases, increased. Similarly, markers of mitochondrial content and respiration were increased in adipose tissue from ATGL knockout mice independent of changes in the Thr172 phosphorylation of AMPK. Taken together, our data provide evidence that AMPK is not required for the regulation of adipose tissue oxidative capacity in conditions of reduced fatty acid release. [ABSTRACT FROM AUTHOR]

The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2-5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH. [ABSTRACT FROM AUTHOR]

The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo-pituitary-adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH. [ABSTRACT FROM AUTHOR]

The evolution of the melanocortin receptors (MCRs) is linked to the evolution of adrenocorticotrophic hormone (ACTH), the melanocyte-stimulating hormones (MSHs), and their common precursor pro-opiomelanocortin (POMC). The origin of the MCRs and POMC appears to be grounded in the early radiation of the ancestral protochordates. During the genome duplications that have occurred during the evolution of the chordates, the organization plan for POMC was established, and features that have been retained include, the high conservation of the amino acid sequences of α-MSH and ACTH, and the presence of the HFRW MCR activation motif in all of the melanocortin peptides (i.e. ACTH, α-MSH, β-MSH, γ-MSH, and δ-MSH). For the MCRs, the chordate genome duplication events resulted in the proliferation of paralogous receptor genes, and a divergence in ligand selectivity. While most gnathostome MCRs can be activated by either ACTH or the MSHs, teleost and tetrapod MC2R orthologs can only be activated by ACTH. The appearance of the accessory protein, MRAP1, paralleled the emergence of teleost and tetrapods MC2R ligand selectivity, and the dependence of these orthologs on MRAP1 for trafficking to the plasma membrane. The accessory protein, MRAP2, does not affect MC2R ligand selectivity, but does influence the functionality of MC4R orthologs. In this regard, the roles that these accessory proteins may play in the physiology of the five MCRs (i.e. MC1R, MC2R, MC3R, MC4R, and MC5R) are discussed. [ABSTRACT FROM AUTHOR]

Proopiomelanocortin (POMC) is a complex precursor that comprises several peptidic hormones, including melanocyte-stimulating hormones (MSHs), adrenocorticotropic hormone (ACTH), and β-endorphin. POMC belongs to the opioid/orphanin gene family, whose precursors include either opioid (YGGF) or the orphanin/nociceptin core sequences (FGGF). This gene family diversified during early tetraploidizations of the vertebrate genome to generate four different precursors: proenkephalin (PENK), prodynorphin (PDYN), and nociceptin/proorphanin (PNOC) as well as POMC, although both PNOC and POMC seem to have arisen due to a local duplication event. POMC underwent complex evolutionary processes, including internal tandem duplications and putative coevolutionary events. Controversial and conflicting hypotheses have emerged concerning the sequenced genomes. In this article, we summarize the different evolutionary hypotheses proposed for POMC evolution. [ABSTRACT FROM AUTHOR]

Many important fields of research had a humble origin. In the distant past, A J P Martin's discovery that amino acids could be separated by paper chromatography and Moore and Stein's use of columns for quantitative amino acid analysis provided the first steps towards the determination of structure in complex biologically active molecules. They opened the door to reveal the essential relationship that exists between structure and function. In molecular endocrinology, for example, striking advances have been made by chemists with their expertise in the identification of structure working with biologists who contributed valuable knowledge and experience. Advantage was gained from the convergence of different background, and it is notable that the whole is greater than the sum. In the determination of structure, it may be recalled that four of the world's great pioneers (Archibald Martin, Rodney Porter, Fred Sanger and Vincent du Vigneaud) were acknowledged for their fundamental contributions when individually they were awarded the Nobel Prize. They foresaw that the identification of structure would prove of outstanding importance in the future. Indeed, study of the structures of β-endorphin and enkephalin and the different forms of opiate activity they engender has led to a transformation in our understanding of chemical transmission in the brain. [ABSTRACT FROM AUTHOR]

The peptide hormones contained within the sequence of proopiomelanocortin (POMC) have diverse roles ranging from pigmentation to regulation of adrenal function to control of our appetite. It is generally acknowledged to be the archetypal hormone precursor, and as its biology has been unravelled, so too have many of the basic principles of hormone biosynthesis and processing. This short review focuses on one group of its peptide products, namely, those derived from the N-terminal of POMC and their role in the regulation of adrenal growth. From a historical and a personal perspective, it describes how their role in regulating proliferation of the adrenal cortex was identified and also highlights the key questions that remain to be answered. [ABSTRACT FROM AUTHOR]

The NETWORK-Lipolysis has played a major role in the development of the minimally invasive alternative therapy for reducing minor deposits of fat which is known today as Injection Lipolysis (IL). Since the introduction of the standard protocol for Injection Lipolysis in 2004, the process of collaboration between a large number of colleagues has led to continuing improvement and adjustment of the protocol. The resulting continuous improvement in the treatment outcomes and the fall in the level of sideeffects has led to strong acceptance on the part of the treating practitioners and patients. [ABSTRACT FROM AUTHOR]

Spontaneous lipolysis was found to be increased in adipocytes of rats with alloxan-induced diabetes. In addition, isoproterenol-stimulated hydrolysis of triacylglycerols was inhibited against the background of oxidative stress and decreased redox-status of cells. A decrease in the ability of insulin to inhibit isoproterenol-stimulated lipolysis in adipocytes that were isolated from adipose tissue of rats with experimental diabetes was found, which shows a disorder in regulation of lipolysis in adipocytes by the hormone in alloxan-induced diabetes. Based on these findings, we concluded that there is an influence of reactive oxygen species, superoxide anion radical in particular, and redox potential of the glutathione system on molecular mechanisms of change in lipolysis intensity in rat adipocytes in alloxan-induced oxidative stress. Activation of spontaneous lipolysis under conditions of oxidative stress might be a reason for the high concentration of free fatty acids in blood plasma in experimental diabetes, and this may play a significant role in development of insulin resistance and appearance of complications of diabetes [ABSTRACT FROM AUTHOR]

Background: Since the first studies by Apfelberg in 1994 and the mathematical model by Mordon in 2004, laser lipolysis (LAL) has been on the rise. Laser lipolysis has the advantages of reduced operator fatigue, excellent patient tolerance, quick recovery time, as well as the additional benefit of dermal tightening. This article reports our experience with laser-assisted lipolysis (LAL) in submental and neck remodelling. Methods: Between June 2010 and January 2013, a prospective study was performed on 30 patients treated for Rohrich type I to III aging neck, with LAL. The laser used in this study was a 980 nm diode laser (Quanta system, spa model D-plus, Solbate Olona (VA), Italy). Laser energy was transmitted through a 600 μm optical fiber and delivered in a continuous mode 15 W power. Previous mathematical modelling suggested that 0.1 kJ was required in order to destroy 1 ml of fat. Patients were asked to fill out a satisfaction questionnaire. The cervicomental angle was measured 6 months post-operatively and compared with the preoperative values. Results: Other than three patients who developed mild hyperpigmentation that disappeared after 4 months, there were no complications in the series. Pain during the anaesthesia and discomfort after the procedure were minimal. The time taken to return to normal activities was 3.2 ± 1 days. All patients would strongly recommend this treatment. Overall satisfaction was high with both patients and investigators and was validated by decrease in cervicomental angle demonstrating a systematic decrease in fat thickness and improved skin tightening. Conclusion: LAL is a safe and reproducible technique for remodeling in Rohrich type I to III aging neck. The procedure allows for a reduction in the amount of adipose deposits while providing concurrent skin contraction. [ABSTRACT FROM AUTHOR]

α -Synuclein ( α S) is a natively disordered protein in solution, thought to be involved in the fusion of neurotransmitter vesicles to cellular membranes during neurotransmission. Monomeric α S has been previously characterized in two distinct membrane-associated conformations: a broken-helix structure, and an extended helix. By employing atomistic molecular dynamics and a novel membrane representation with significantly enhanced lipid mobility (HMMM), we investigate the process of spontaneous membrane binding of α S and the conformational dynamics of monomeric α S in its membrane-bound form. By repeatedly placing helical α S monomers in solution above a planar lipid bilayer and observing their spontaneous association and its spontaneous insertion into the membrane during twenty independent unbiased simulations, we are able to characterize α S in its membrane-bound state, suggesting that α S has a highly variable membrane insertion depth at equilibrium. Our simulations also capture two distinct states of α S, the starting broken-helix conformation seen in the micelle bound NMR structures, and a semi-extended helix. Analysis of lipid distributions near α S monomers indicates that the transition to a semi-extended helix is facilitated by concentration of phosphatidyl-serine headgroups along the inner edge of the protein. Such a lipid-mediated transition between helix–turn–helix and extended conformations of α S may also occur in vivo, and may be important for the physiological function of α S. [ABSTRACT FROM AUTHOR]

Introduction. This sports-science-related article heavily relies on studies that have reported an increase in beta-endorphin (β-EP) concentration in plasma in response to physical activity. It examines the psychological and physiological effects of physical activity and exercise and reports on a research-experiment-based, endorphin-hypotheses-related pilot study aimed at exploring mood-related β-EP effects occurring in physically active male and female individuals aged 45-55 in response to physical load. Material and methods. Six 45 to 55-year-old individuals (3 males and 3 females) rated as exhibiting moderate and high levels of physical activity in sport's laboratory. International Physical Activity Questionnaire (IPAQ) was used to establish physical activity level. For facial expression analysis a short interview was applied, using software ''FaceReader 3.0'' (FR). As a load test a veloergometer exercise test was used, and Beta-endorphin (β-EP) levels were measured from venous blood. Results. The findings demonstrated an increase in β-EP levels in 50% of the subjects. No positive relation between β-EP increase and happiness has been observed. In four subjects an increase in disgust was observed due to the laboratory conditions. Five minutes after the load test FR data recorded the reduction or disappearance of negative emotions for all research subjects. Conclusions. Further investigation into the relationship of plasma levels of β-EP and the emotional state of the individual involved in physical activities is needed. This necessitates a further insight into how exercise-elevated endorphins (β-EP) affect mood state outside laboratory conditions. Therefore, a further investigation of people involved in physical recreation activities outdoors is envisaged. [ABSTRACT FROM AUTHOR]

The neuropeptide, α-calcitonin gene-related peptide (α-CGRP), is expressed from sensory nerves that innervate fat. However, how α-CGRP may act in adipose tissue is unclear. Using 3T3-L1 adipocytes we observed that rat α-CGRP (rα-CGRP) evoked either a biphasic or monophasic reduction in intracellular free fatty acid (FFA) content. cAMP production was always monophasic and occurred when FFA responses were absent. Taken together with the observed potencies, these findings suggest that adipose tissue is a physiological target for α-CGRP. However, uncoupling of the FFA and CGRP-signaling responses with increasing passage number limits 3T3-L1 adipocytes as a suitable cellular model. [ABSTRACT FROM AUTHOR]

Abstract: Adipose triglyceride lipase (ATGL) is required for efficient mobilization of triglyceride (TG) stores in adipose tissue and non-adipose tissues. Therefore, ATGL strongly determines the availability of fatty acids for metabolic reactions. ATGL activity is regulated by a complex network of lipolytic and anti-lipolytic hormones. These signals control enzyme expression and the interaction of ATGL with the regulatory proteins CGI-58 and G0S2. Up to date, it was unknown whether ATGL activity is also controlled by lipid intermediates generated during lipolysis. Here we show that ATGL activity is inhibited by long-chain acyl-CoAs in a non-competitive manner, similar as previously shown for hormone-sensitive lipase (HSL), the rate-limiting enzyme for diglyceride breakdown in adipose tissue. ATGL activity is only marginally inhibited by medium-chain acyl-CoAs, diglycerides, monoglycerides, and free fatty acids. Immunoprecipitation assays revealed that acyl-CoAs do not disrupt the protein–protein interaction of ATGL and its co-activator CGI-58. Furthermore, inhibition of ATGL is independent of the presence of CGI-58 and occurs directly at the N-terminal patatin-like phospholipase domain of the enzyme. In conclusion, our results suggest that inhibition of the major lipolytic enzymes ATGL and HSL by long-chain acyl-CoAs could represent an effective feedback mechanism controlling lipolysis and protecting cells from lipotoxic concentrations of fatty acids and fatty acid-derived lipid metabolites. [Copyright &y& Elsevier]

Cankles refer to the area where the calf and ankle meet. Unaesthetic fat cankles, where definition between the calf and ankle is impossible, are a frustrating aesthetic deformity, which are exacerbated by their genetic conditioning and special resistance to diet. This article reports our experience with laser-assisted lipolysis (LAL) in cankle remodelling. A total of 30 patients were treated for unaesthetic fat cankles with LAL. The 924/975-nm diode laser used in this study consisted of two lasers, one emitting at 924 nm, and the other at 975 nm. According to our mathematical models, we assumed that to destroy 1 ml of fat, 0.1 kJ was required in dual emission mode at 924/975 nm. Patients were asked to file a satisfaction questionnaire. Ultrasound was used to measure the fat thickness pre- and postoperatively. Oedema in both lateral sulcus of the Achilles tendon was seen in all patients. It subsided after 4 weeks in nine cases and 6 weeks in 21 cases. Only two patients developed mild hyperpigmentation that disappeared, respectively, after 4 and 10 weeks. Pain during the anaesthesia and discomfort after the procedure were low with this technique. Mean down time was 1.0 day. Of the 30 patients, 29 would recommend this treatment. Overall, high patient and investigator satisfaction was confirmed by the sonography used to measure decrease in fat thickness. LAL in cankle remodelling is a safe and reproducible technique that is particularly appreciated by the patient. The procedure allows homogenous reduction of fatty tissue together with skin tightening. [ABSTRACT FROM AUTHOR]

Although biochemical and physiological evidence suggests a strong interaction between striatal CB1 cannabinoid (CB1R) and D2 dopamine (D2R) receptors, the mechanisms are poorly understood. We targeted medium spiny neurons of the indirect pathway using shRNA to knockdown either CB1R or D2R. Chronic reduction in either receptor resulted in deficits in gene and protein expression for the alternative receptor and concomitantly increased expression of the cannabinoid receptor interacting protein 1a (CRIP1a), suggesting a novel role for CRIP1a in dopaminergic systems. Both CB1R and D2R knockdown reduced striatal dopaminergic-stimulated [35S]GTPγS binding, and D2R knockdown reduced pallidal WIN55212-2-stimulated [35S]GTPγS binding. Decreased D2R and CB1R activity was associated with decreased striatal phosphoERK. A decrease in mRNA for opioid peptide precursors pDYN and pENK accompanied knockdown of CB1Rs or D2Rs, and over-expression of CRIP1a. Down-regulation in opioid peptide mRNAs was followed in time by increased DOR1 but not MOR1 expression, leading to increased [D-Pen2, D-Pen5]-enkephalin-stimulated [35S]GTPγS binding in the striatum. We conclude that mechanisms intrinsic to striatal medium spiny neurons or extrinsic via the indirect pathway adjust for changes in CB1R or D2R levels by modifying the expression and signaling capabilities of the alternative receptor as well as CRIP1a and the DELTA opioid system. [ABSTRACT FROM AUTHOR]

Growth regulation in adult Atlantic salmon (1.6 kg) was investigated during 45 days in seawater at 13, 15, 17, and 19 °C. We focused on feed intake, nutrient uptake, nutrient utilization, and endocrine regulation through growth hormone (GH), insulin-like growth factors (IGF), and IGF-binding proteins (IGFBP). During prolonged thermal exposure, salmon reduced feed intake and growth. Feed utilization was reduced at 19 °C after 45 days compared with fish at lower temperatures, and body lipid storage was depleted with increasing water temperature. Although plasma IGF-1 concentrations did not change, 32-Da and 43-kDa IGFBP increased in fish reared at ≤17 °C, and dropped in fish reared at 19 °C. Muscle igf1 mRNA levels were reduced at 15 and 45 days in fish reared at 15, 17, and 19 °C. Muscle igf2 mRNA levels did not change after 15 days in response to increasing temperature, but were reduced after 45 days. Although liver igf2 mRNA levels were reduced with increasing temperatures after 15 and 45 days, temperature had no effect on igf1 mRNA levels. The liver igfbp2b mRNA level, which corresponds to circulating 43-kDa IGFBP, exhibited similar responses after 45 days. IGFBP of 23 kDa was only detected in plasma in fish reared at 17 °C, and up-regulation of the corresponding igfbp1b gene indicated a time-dependent catabolic response, which was not observed in fish reared at 19 °C. However, higher muscle ghr mRNA levels were detected in fish at 17 and 19 °C than in fish at lower temperatures, indicating lipolytic regulation in muscle. These results show that the reduction of muscle growth in large salmon is mediated by decreased igf1 and igf2 mRNA levels in addition to GH-associated lipolytic action to cope with prolonged thermal exposure. Accordingly, 13 °C appears to be a more optimal temperature for the growth of adult Atlantic salmon at sea. [ABSTRACT FROM AUTHOR]

Intense lipid mobilization during the transition period in dairy cows is associated with increased disease susceptibility. The potential impact of altered plasma nonesterified fatty acids (NEFA) concentrations and composition on host inflammatory responses that may contribute to disease incidence and severity are not known. The objective of this study was to evaluate if increased NEFA concentrations could modify vascular inflammatory responses in vitro by changing the expression of important inflammatory mediators that are important in the pathogenesis of infectious diseases of transition cows such as mastitis and metritis. Bovine aortic endothelial cells (BAEC) were cultured with different concentrations of a NEFA mixture that reflected the plasma NEFA composition during different stages of lactation. The expression of cytokines, adhesion molecules, and eicosanoids were measured to assess changes in BAEC inflammatory phenotype. Addition of NEFA mixtures altered the fatty acid profile of BAEC by increasing the concentration of stearic acid (C18:0) and decreasing the content of arachidonic acid (C20:4n6c) and other long-chain polyunsaturated fatty acids in the phospholipid fraction. A significant increase also occurred in mRNA expression of cytokine and adhesion molecules that are associated with increased inflammatory responses during the transition period. Expression of cyclooxygenase 2, an important enzyme associated with eicosanoid biosynthesis, was increased in a NEFA concentration-dependent manner. The production of linoleic acid-derived eicosanoids 9- and 13-hydroxyoctadecadienoic acids also was increased significantly after treatment with NEFA mixtures. This research described for the first time specific changes in vascular inflammatory response during in vitro exposure to NEFA mixtures that mimic the composition and concentration found in cows during the transition period. These findings could explain, in part, alterations in inflammatory responses observed during intense lipid mobilization stages such as in the transition period of dairy cows. Future studies should analyze specific mechanisms by which high NEFA concentrations induce a vascular proinflammatory phenotype including the effect of 9 and 13-hydroxyoctadecadienoic acids and other lipid mediators. [ABSTRACT FROM AUTHOR]

Background In the United States, liposuction is the most commonly performed cosmetic surgical procedure. Laser lipolysis is the latest adjunct to liposuction. This technique employs laser energy to induce lipolysis and hemostasis and stimulate neocollagenesis. Multiple laser systems have been studied. Methods Pub Med literature search with the key words laser lipolysis and laser assisted liposuction. Original articles that studied the internal application of laser energy to adipose tissue were reviewed and included. Results Nineteen manuscripts were reviewed. One double-blind randomized controlled trial compared laser liposuction with tumescent liposuction. Several authors claimed that laser lipolysis offers fewer side effects than 'traditional' liposuction performed under general anesthesia. A true objective comparison with tumescent liposuction is missing in the literature. Limitations Comparison studies between laser-assisted lipolysis and conventional liposuction are limited, as are comparisons between the different laser systems and wavelengths. Standardization of laser energy settings is lacking. Conclusion Laser-assisted lipolysis is a safe and efficacious procedure that may possess advantages over conventional liposuction. Lipolysis occurs in a dose-response relationship. No advantage over tumescent liposuction has been demonstrated. A specific laser wavelength may prove superior for each clinical application, but more studies are needed. [ABSTRACT FROM AUTHOR]

Background: Dietary supplements are often marketed to increase lipolysis and thermogenesis, with the proposed end result being weight loss and body fat reduction. It was the purpose of the present investigation to study the acute effects of a weight/fat loss supplement within a sample of healthy human subjects. Methods: Twelve subjects (men 24.8 ± 4.3 yrs; women 22.8 ± 0.4 yrs) ingested a dietary supplement (OxyELITE ProTM) or a placebo, on two separate days in a double-blind, cross-over design. Blood samples were collected immediately before ingestion, and at 60 and 120 minutes post ingestion, and analyzed for plasma glycerol and free fatty acids (FFA). Breath samples were collected immediately before ingestion and at 30, 60, 90, and 120 minutes post ingestion, for a measure of kilocalorie expenditure using indirect calorimetry. Area under the curve (AUC) was calculated. Heart rate and blood pressure were recorded at all times and rate pressure product (RPP) was calculated. Results: AUC was greater for supplement compared to placebo for glycerol (22.74 ± 1.98 µg ·mL-1· 2 hr-1 vs. 15.76 ± 1.36 µg·mL-1·2 hr-1; P = 0.001), FFA (1.62 ± 0.07 mmol · L-1·2 hr-1 vs. 0.78 ± 0.12 mmol·L-1· 2 hr-1; P < 0.0001), and kilocalorie expenditure (149 ± 7 kcal· 2 hr-1 vs. 122 ± 8 kcal· 2 hr-1; P = 0.005). Heart rate (P = 0.02), systolic blood pressure (P < 0.0001), and RPP (P = 0.002) were higher for supplement compared to placebo. Conclusion: Ingestion of OxyELITE ProTM resulted in an increase in blood markers of lipolysis, as well as metabolic rate, during a two-hour post ingestion time period. An increase in hemodynamic variables was also observed. These findings are in reference to a sample of healthy men and women who were naïve to treatment with the dietary supplement. Additional work is needed to determine if the acute changes observed here would persist with chronic use of the supplement and possibly lead to weight/body fat loss over time. [ABSTRACT FROM AUTHOR]

The peptides encoded by the VGF gene are gaining biomedical interest and are increasingly being scrutinized as biomarkers for human disease. An endocrine/neuromodulatory role for VGF peptides has been suggested but never demonstrated. Furthermore, no study has demonstrated so far the existence of a receptor-mediated mechanism for any VGF peptide. In the present study, we provide a comprehensive in vitro, ex vivo and in vivo identification of a novel pro-lipolytic pathway mediated by the TLQP-21 peptide. We show for the first time that VGF-immunoreactivity is present within sympathetic fibres in the WAT (white adipose tissue) but not in the adipocytes. Furthermore, we identified a saturable receptor-binding activity for the TLQP-21 peptide. The maximum binding capacity for TLQP-21 was higher in the WAT as compared with other tissues, and selectively up-regulated in the adipose tissue of obese mice. TLQP-21 increases lipolysis in murine adipocytes via a mechanism encompassing the activation of noradrenaline/β-adrenergic receptors pathways and dose-dependently decreases adipocytes diameters in two models of obesity. In conclusion, we demonstrated a novel and previously uncharacterized peripheral lipolytic pathway encompassing the VGF peptide TLQP-21. Targeting the sympathetic nerve–adipocytes interaction might prove to be a novel approach for the treatment of obesity-associated metabolic complications. [ABSTRACT FROM AUTHOR]

Abstract: An octapeptide of the adipokinetic hormone (AKH) peptide family is identified in the corpora cardiaca of the stink bug, Nezara viridula, by ESI-MS N (electrospray ionization multistage MS). This is the second AKH in N. viridula and it has a hydroxyproline residue at position 6, whereas the major AKH (known as Panbo-RPCH) has Pro as the sixth amino acid residue. The correct sequence assignment of [Hyp6]-Panbo-RPCH is confirmed by retention time and MS spectra of the synthetic peptide. Various extraction procedures were followed to ascertain whether the hydroxylation is an artefact of extraction, or whether it is due to a true post-translational modification at the prohormone level. The proline hydroxylation is unique for invertebrate neuropeptides, while it has been described in the vertebrate gonadotropin-releasing hormone (GnRH). The current finding is another piece of evidence that AKH and GnRH form a peptide superfamily and are closely related evolutionarily. Biologically, [Hyp6]-Panbo-RPCH is active in vivo as an AKH, causing hyperlipaemia in the stink bug at low doses, indicating again that it is an endogenous, mature and functional hormone in this insect species. [Copyright &y& Elsevier]

The potencies of natural adipokinetic hormones and synthetic variants (short peptides) have been obtained in Locusta migratoria. This short peptides (a total of sixty-nine analogues) data was used to construct the mathematical models of the hormone potencies. The sequence variations of amino acids in both natural and artificial adipokinetic hormone analogues were characterized by using a set of descriptors proposed in our laboratory, then QSAR models were developed successfully by using orthogonal signal correction combines with partial least squares (OSC-PLS) method. The cross validation correlation coefficients ( Q) were up to 0.942. The results show that the descriptors proposed in this study will be useful in structure characterization and activity prediction of biological molecules. [ABSTRACT FROM AUTHOR]

Background: Vaspin was a recently identified adipokine, playing a protective role in many metabolic diseases. The present study aimed to investigate the association between vaspin plasma level and stable angina pectoris (SAP) and unstable angina pectoris (UAP). Methods: A total of 88 patients with angiographically-proved coronary artery disease (CAD) (SAP 47, UAP 41) and 103 control subjects without cardiovascular diseases were enrolled in this study. Circulating vaspin, mRNA expression of vaspin in peripheral blood mononuclear cells (PBMC), clinical parameters, lipid profile and high-sensitivity C-reactive protein (hsCRP) were assayed. The severity of CAD was also assessed according to the number of vessels diseased. Results: There are significant differences in circulating vaspin levels and mRNA levels of PBMC between SAP and UAP groups (SAP 0.91±0.95 ng/mL and UAP 0.43±0.38 ng/mL, p<0.01 in circulating vaspin level; SAP 1.19±0.85 and UAP 0.82±0.56, p<0.05 in mRNA level of PBMC). An inverse correlation between the number of diseased vessels and plasma vaspin concentration was observed (r =-0.350, p<0.01) in the CAD group. Construction of receiver operating characteristic curves confirmed that vaspin plasma concentrations significantly differentiated CAD patients (area under the curve=0.684, p<0.001), as well as UAP (area under the curve=0.640, p<0.05). Conclusion: Decreased vaspin plasma levels and mRNA levels in PBMC were observed in patients with UAP. Low vaspin concentrations correlate with CAD severity. The findings suggested that vaspin could serve as a novel biomarker of CAD as well as UAP. [ABSTRACT FROM AUTHOR]

Summary Objective Apelin is an adipokine secreted from adipose and other tissues with increased expression in obesity, role in glucose metabolism and atherosclerosis, as well as in oxidative stress. Pregnancy is considered a state of hyperlipidemia, oxidative stress and decreased insulin sensitivity. The aim of the present study is to investigate the levels of apelin in human pregnancy and its relation to insulin sensitivity. Patients and measurements One hundred and six pregnant women (24th-28th week of gestation), aged 27·9 ± 0·4 years, were compared to 106 age-matched healthy, nonpregnant women (controls). Measured parameters included serum levels of glucose, insulin, apelin, adiponectin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), triglycerides and oxidized LDL (ox-LDL). The body mass index (BMI) and the quantitative insulin sensitivity check index (QUICKI) were calculated as well. Results BMI, serum lipids and insulin levels were significantly higher, whereas serum apelin and glucose levels were lower in the pregnancy group compared to the control group. There was a significant negative correlation between apelin and adiponectin, in both groups. Additionally, apelin was negatively correlated with ox-LDL and HDL-cholesterol in the pregnancy group. Conclusions Although strongly correlated with adiponectin, apelin cannot be used as a marker of insulin sensitivity, but it could serve as a marker of oxidative stress in pregnancy. [ABSTRACT FROM AUTHOR]

Resistin is an adipokine that induces insulin resistance in mice. In humans, resistin is not produced in adipocytes, but in various leukocytes instead, and it acts as a proinflammatory molecule. The present investigation demonstrated high levels of resistin in culture supernatants of neutrophils that are stimulated by a highly leukotoxic strain of Aggregatibacter actinomycetemcomitans. In contrast, the level of resistin was remarkably low when neutrophils were exposed to two other strains that produce minimal levels of leukotoxin and a further isogenic mutant strain incapable of producing leukotoxin. Pretreatment of neutrophils with a monoclonal antibody to CD18, β chain of lymphocyte function-associated molecule 1 (LFA-1), or an Src family tyrosine kinase inhibitor before incubation with the highly leukotoxic strain inhibited the release of resistin. These results show that A. actinomycetemcomitans-expressed leukotoxin induces extracellular release of human neutrophil-derived resistin by interacting with LFA-1 on the surface of neutrophils and, consequently, activating Src family tyrosine kinases. [ABSTRACT FROM AUTHOR]

pelin (AP) and leptin (LEP) are adipokines with vasomotor actions. Taking into account the published data on the role of obesity in the development of pulmonary hypertension, we studied the implications of apelin on leptin relaxing effects on isolated rat pulmonary arteries. LEP had vasodilatatory effects on phenylephrine-precontracted rat pulmonary arteries from normal and ovalbumin-sensitized rats, but not on rats with monocrotaline-induced pulmonary hypertension. AP13 pretreatment increased LEP effects by one-half. Our studies revealed the existence of synergistic favorable effects of these adipokines on pulmonary vessels. [ABSTRACT FROM AUTHOR]

Adipose stromal cells (ASCs) serve as mesenchymal progenitors in white adipose tissue (WAT). Intercellular interactions involving ASCs have remained obscure. By merging phage display technology with fluorescence-activated cell sorting (FACS), we screened a combinatorial library for peptides that target mouse ASCs in vivo. We isolated peptide CSWKYWFGEC that specifically homes to ASCs, used it as bait to purify the corresponding ASC surface receptor, and identified it as a previously unreported cleavage product of decorin (DCN) lacking the glycanation site (termed ΔDCN). We demonstrate that ΔDCN is differentially expressed on ASC surface. In a screen for ΔDCN-binding proteins, we identified resistin, an adipokine for which the receptor has been unknown. Expression of ΔDCN in 3T3-L1 cells promoted proliferation and migration but suppressed lipid accumulation upon adipogenesis induction, which was resistin dependent. We conclude that ΔDCN serves as a functional receptor of resistin in adipocyte progenitors and may regulate WAT expansion. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to investigate the allelic frequency of the G308A polymorphism in the TNF alpha gene and the influence of G308A this polymorphism on cardiovascular risk factors and adipokine levels in obese patients. Design: A population of 834 obesity patients was analyzed. A nutritional evaluation and a blood analysis were performed. The statistical analysis was performed for the combined G308A and A308A as mutant group and type G308Gas wild group. Results: A total of 630 patients (181 males/449 females) (75.5%) had the genotype G308/G308 (wild genotype group) with an average age of 43.5 ± 14.8 years, 188 patients (61 males/127 females) (22.5%) had the genotype G308/A308 (mutant genotype group-heterozygote) and 16 patients (5 males/11 females) (1.9%) with an average age of 44.5 ± 14.2 years had the genotype X308/A308 (mutant group-homorozygote) with an average age of 44.3 ± 11.4 years, without statistical differences in the mean age or sex distribution. Genotypes G308/A308 and A308/A308 was designed (mutant genotype group) as a dominant model. Allelic frequency of the A substitución -308 was 13.19%. Anthropometric, adipokines, insulin resistance, lipid levels ad dietary intake were similar in both genotypes. Conclusion: In conclusion, allelic frequency of G308A polymorphism is is in accordance with allelic frequencies observed in other populations. Carries of A308 allele have the same anthropometric and metabolic profile than wild type carriers. [ABSTRACT FROM AUTHOR]

Abstract: The Herring gull (HG) (Larus argentatus) is naturally exposed to halogenated organic compounds such as polychlorinated biphenyls (PCBs) through its diet. During periods of food scarcity, arctic seabirds experience lipid mobilization, allowing stored lipid soluble contaminants to re-enter the body circulation. In the present study, we investigated the effects of PCB exposure and fasting on the antioxidant defense system in HG chicks. Forty newly hatched chicks were exposed to contaminated cod liver oil for 6weeks and then fasted for 1week. We assessed the hepatic total oxyradical scavenging capacity (TOSC) against peroxynitrite, hydroxyl and peroxyl radicals, and measured glutathione (reduced: GSH, and oxidized: GSSG) levels and the enzymatic activities of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase. The results show that fasting significantly increased the HOC levels in the HG chick livers. Limited effects were observed on antioxidant responses; significant effects were only found for catalase (CAT) activity, Se-dependent GPX activity and the GSH/GSSG ratio in the exposed and fasted group. CAT and Se-dependent GPX activities correlated negatively with the PCB concentrations within this group, and a nonlinear relationship between glutathione and contaminant levels was also found. These effects were generally not observed after exposure or fasting alone and were likely related to the high PCB levels induced by the combination of exposure and fasting. [Copyright &y& Elsevier]

Objective: The current study evaluated multiple metabolic and inflammatory hormone responses in recreational climbers (7 men and 3 women, age 26–49 years) over 9 days. In particular, acylation-stimulating protein (ASP), which influences fat storage in adipose tissue, has not been measured at high altitude. Methods: Serial measurements were taken at sea level (SL), or 353 m, on day 0, 4000 m on day 3, 4750 m on day 6, and 5300 m on day 9 of the expedition. Results: Body mass index (BMI) decreased upon ascent to 5300 m from SL (SL 23.2 ± 1.5 kg/m2; 4000 m 23.2 ± 1.4 kg/m2; 4750 m 22.9 ± 1.3 kg/m2; 5300 m 22.3 ± 1.2 kg/m2; P < .001). Similarly, plasma non-esterified fatty acids and triglycerides increased, while HDL cholesterol decreased (P < .05 to < .001) from SL to 5300 m. Acylation-stimulating protein (SL 42.2 ± 40.2 nm; 4000 m 117.0 ± 69.6 nm; 4750 m 107.9 ± 44.5 nm; 5300 m 82.2 ± 20.2 nm; P = .019) and adiponectin (SL 10.4 ± 6.5 ng/mL, 4000 m 13.9 ± 8.5 ng/mL, 4750 m 18.3 ± 8.3 ng/mL, 5300 m 14.7 ± 8.0 ng/mL; P = .015) increased, as did insulin and Interleukin-6 (IL-6) levels (up to 71% and 168%, respectively; P < .05) with no change in leptin, complement C3 (C3), high sensitivity C-reactive protein (hsCRP) or cortisol levels throughout the mountain ascent from SL to 5300 m. Conclusion: Acylation-stimulating protein and adiponectin are increased during a 9-day period of high altitude (SL to 5300 m) exposure despite weight loss in healthy mountaineers. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is associated with morbidity and mortality of heart failure. Eicosapentaenoic acid (EPA), which is contained in fish oil, was shown to reduce the risk of cardiovascular diseases. We investigated the effects of EPA on AF associated with heart failure in a rabbit model. Rabbits were subjected to ventricular tachypacing (VTP) for 4 wk with or without EPA treatment. Continuous VTP induced heart failure status in these rabbits. The duration of AF (DAF) induced by burst pacing was analyzed by electrophysiological studies. VTP resulted in increased DAF following burst pacing. EPA treatment attenuated increased DAF. Atrial fibrosis increased in response to VTP, accompanied by extracellular signal-regulated kinase (ERK) phosphorylation and transforming growth factor-β1 (TGF-β1) expression in the atrium. Treatment with EPA attenuated atrial fibrosis, ERK phosphorylation, and TGF-β1 expression in response to VTP. EPA treatment increased adiponectin as an anti-inflammatory adipokine and decreased tumor necrosis factor-α as a proinflammatory adipokine in the atrium and epicardial adipose tissues. EPA attenuated VTP-induced AF promotion and atrial remodeling, which was accompanied by modulating the profiles of adipokine production from epicardial adipose tissue. EPA may be useful for prevention and treatment of AF associated with heart failure. [ABSTRACT FROM AUTHOR]

Objective:To investigate the anti-obesity effect of the adipokine zinc-α2-glycoprotein (ZAG) in rats and the mechanism of this effect.Subjects:Mature male Wistar rats (540±83 g) were administered human recombinant ZAG (50 μg per 100 g body weight given intravenously daily) for 10 days, while control animals received an equal volume of phosphate-buffered saline (PBS).Results:Animals treated with ZAG showed a progressive decrease in body weight, without a decrease in food and water intake, but with a 0.4 °C rise in body temperature. Body composition analysis showed loss of adipose tissue, but an increase in lean body mass. The loss of fat was due to an increase in lipolysis as shown by a 50% elevation of plasma glycerol, accompanied by increased utilization of non-esterified fatty acids, as evidenced by the 55% decrease in plasma levels. Plasma levels of glucose and triglycerides were also reduced by 36-37% and there was increased expression of the glucose transporter 4 in both skeletal muscle and adipose tissue. Expression of the lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase in the white adipose tissue (WAT) were increased twofold after ZAG administration. There was almost a twofold increased expression of uncoupling proteins 1 and 3 in brown adipose tissue and WAT, which would contribute to increased substrate utilization. Administration of ZAG increased ZAG expression twofold in the gastrocnemius muscle, BAT and WAT, which was probably necessary for its biological effect.Conclusion:These results show that ZAG produces increased lipid mobilization and utilization in the rat. [ABSTRACT FROM AUTHOR]

The adipose tissue is a highly regulated endocrine and paracrine organ that secretes a wide variety of biologically active molecules involved in the control of energy balance and the regulation of body weight. Our work aimed to analyze the dysregulation of the adipocyte metabolism and compare the gene expression patterns between omental (OM) and subcutaneous (SC) adipose tissue from obese and lean subjects by using whole-genome DNA microarrays. OM and SC adipose tissues were obtained from 43 obese subjects undergoing bariatric surgery and from six lean individuals. Gene expression analysis was performed by whole-genome microarrays and Taqman RT-PCR. The analysis of microarrays showed upregulation of 545 genes in OM and 47 in SC adipose tissue, whereas 723 and 27 genes were downregulated in OM and SC tissue, respectively, in obese patients. Significantly altered genes showed at least a twofold change of p < 0.05. Validation of the arrays with 28 genes was carried out by using low density microfluidic cards which confirmed the changes found in most genes. We focused on the altered expression of gene coding for enzymes and transcription factors involved in lipid metabolism. Interestingly, some of these genes have not been previously described in obesity. Our results show that adipose tissue from obese subjects entails defense mechanisms against an excessive expansion and fat accumulation, repressing both lipogenesis and lipolysis. [ABSTRACT FROM AUTHOR]

Abstract: Adipose tissue mass in mammals expands by increasing both volume and total number of the adipocytes. The simultaneous existence of large and small adipocytes and their unsynchronized growth, even within the same adipose tissue depot, argues against simple filling-up of nascent small adipocytes with lipids and lipid droplets. Consequently, it is tempting to speculate about signals provoking shift of lipid loading from mature large to small adipocytes. Very recently, microvesicles have been shown (i) to harbor the glycosylphosphatidylinositol-anchored (c)AMP-degrading phosphodiesterase Gce1 and the 5′-nuceotidase CD73, (ii) to be released (preferably) from large adipocytes, (iii) to interact (preferably) with small adipocytes and (iv) to transfer Gce1 and CD73 to plasma membranes and lipid droplets of the small adipocytes where they degrade (c)AMP. This sequence of events leads to upregulation of lipid storage in small adipocytes in response to the microvesicle-encoded “take-over” signal from large adipocytes. A model is proposed for the maturation of small adipocytes driven by large cells along a gradient of microvesicle-derived inter-adipocyte signals. Pharmacological modulation of the communication between adipocytes for their maturation may be useful for the therapy of metabolic diseases. [Copyright &y& Elsevier]

Abstract: Objective: White adipose tissue (WAT) is now considered a defined tissue capable of interactions with other organ systems. WAT role in elevating the level of systemic chronic inflammation suggests that alterations in this tissue as the result of disease or environmental factors may influence the development and progression of various obesity-related pathologies. This study investigated WAT cell-specific responses to an organometal compound, trimethyltin (TMT), to determine possible contribution to induced inflammation. Methods: Human primary mature adipocytes and macrophage differentiated THP-1 cells were cultured in TMT presence and relative toxicities and different adipokine levels were determined. The inflammatory response was examined in TMT presence for primary cells from obese ob/ob mice WAT, and after TMT injection in ob/ob mice. Results: Both adipocytes and macrophages were resistant to cell death induced by TMT. However, adipocytes cultured in TMT presence showed increased expression of TNFα and IL-6, and modified leptin levels. In macrophage cultures, TMT also increased TNFα and IL-6, while MCP-1 and MIP-1α were decreased. In vivo, a single injection of TMT in ob/ob mice, elevated TNFα, MIP-1α and adiponectin in WAT. Conclusions: Elevation of the inflammatory related products can be induced by chemical exposure in adipocytes and macrophages, as well as murine WAT. These data suggest that numerous factors, including a systemic chemical exposure, can induce an inflammatory response from the WAT. Furthermore, when characterizing both chemical-induced toxicity and the progression of the chronic inflammation associated with elevated WAT content, such responses in this target tissue should be taken into consideration. [Copyright &y& Elsevier]

Abstract: We observed diminished lymphoproliferation to multiple stimuli in older women with persistent cervical human papillomavirus (HPV) infection. Adipokines are a class of inflammatory cytokines that are altered in some persistent infections. The objective was to compare the level of adipokines and inflammatory cytokines in heparinized plasma from women with persistent HPV cervical infection (Cases, N =50, oversampled for their weak lymphoproliferation responses) with women with no evidence of persistent HPV cervical infection (Controls, N =50, oversampled for their strong lymphoproliferation responses). Plasma samples were analyzed with multiplex assays for adipokines and inflammatory cytokines. Cases had significantly elevated plasma levels of resistin (p <0.0001) and sFas (p =0.0038) as compared to controls. Risk of persistent HPV infection increased significantly with increasing levels of resistin and 8Fas. This is the first study to demonstrate elevated levels of resistin and sFas in HPV persistently infected, older women with decreased immune function expanding the understanding of the systemic inflammation and immune alterations in individuals persistently infected with HPV. Further studies within a larger cohort are needed to define the generalities of these findings and any role adipokines have in persistent HPV infection. [Copyright &y& Elsevier]

The storage and mobilization of lipid energy are central functions of adipocytes. Lipid energy is stored as triglyceride in lipid droplet structures that are now recognized as hona fide organelles and whose functions are greatly influenced by members of the perilipin family of lipid droplet scaffolds. Recent work indicates that the signaling events underlying fatty acid mobilization involve protein trafficking to a specialized subset of lipid droplets. Furthermore, the core lipolytic machinery is composed of evolutionarily conserved proteins whose functions are conserved in avian and mammalian production species. Lipolysis affects many aspects of animal nutrition and physiology, which can have an important influence on growth efficiency, lactation, and meat quality. This review focuses on recent research that addresses the organization and trafficking of key players in hormone-stimulated lipolysis, and the central role of perilipin 1A in adipocyte lipolysis. The review emphasizes recent work frpm the laboratories of the authors that utilizes imaging techniques to explore the organization and interactions among lipolytic effectors in live cells during lipolytic activation. A mechanistic understanding of lipolysis may lead to new strategies for promoting human and animal health. [ABSTRACT FROM AUTHOR]

Abstract: Gonadotropin-releasing hormone (GnRH) plays a central role in vertebrate reproduction. The evolutionary origin of this neuropeptide and its receptor is not obvious, but the advent of genomics makes it possible to examine the roots of GnRH and delve deeper into its ancestral relationships. New peptide sequences identified in invertebrates from annelids to tunicates reveal GnRH-like peptides of 10–12 amino acids. Structural conservation suggests homology between the 15 known invertebrate peptides and the 15 known vertebrate GnRHs. The functions of the invertebrate GnRH-like peptides are not necessarily related to reproduction. We suggest that structurally related families of invertebrate peptides including corazonin and adipokinetic hormone (AKH) form a superfamily of neuropeptides with the GnRH family. GnRH receptors have also been identified in invertebrates from annelids to tunicates suggesting that the origin of GnRH and its receptor extends deep in evolution to the origin of bilaterian animals. To resolve the relationship of invertebrate and vertebrate receptors, we conducted large-scale phylogenetic analysis using maximum likelihood. The data support a superfamily that includes GnRH, AKH and corazonin receptors derived from both published sequences and unpublished gene model predictions. Closely related to the GnRHR superfamily is the vasopressin/oxytocin superfamily of receptors. Phylogenetic analysis suggests a shared ancestry with deep roots. A functional role for GnRH in vertebrates or invertebrates leads to questions about the evolutionary origin of the pituitary. Our analysis suggests a functioning pituitary was the result of genomic duplications in early vertebrates. [Copyright &y& Elsevier]

Abstract: The average mesopore size of the new Halo-ES-Peptide shell particles is 160Å, markedly larger than that of the classical Halo shell particles (90Å). We found that this change causes a considerable decrease of the film mass transfer resistance measured for columns packed with these particles. We analyze data obtained by systematic measurements of the C term of the van Deemter equation for the peptide β-lipotropin (MW = 769Da), the protein insulin (MW = 5800Da), and a series of non-retained polystyrene standards (MW = 6400 and 13,200). The improvement in column performance is explained by an increase of the fraction of the external surface area of the shell that allows the entrance of the sample molecules inside the particle. The fraction of the shell surface accessible to a probe controls the rate of its external film mass transfer, i.e. its rate of transfer between the interstitial and the stagnant eluent. Although measurable, the increase in sample diffusivity through the porous shells does not account for the better performance of Halo-ES-peptide columns. Furthermore, the analysis of the HETPs data of small molecules (uracil, acetophenone, toluene, and naphthalene, MW < 150) reveals that the eddy diffusion (A) term of these new columns is 25% lower than that of the classical Halo columns. This result is consistent with the impact of intra-particle diffusivity on the eddy diffusion mechanism in packed columns. As shell diffusivity increases, so does the rate of transfer of sample molecules between the eluent stream-paths flowing through the packed particles and across the column diameter. Dispersion through short-range inter-channel and trans-column eddies is reduced. [ABSTRACT FROM AUTHOR]

The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function. [ABSTRACT FROM AUTHOR]

Abstract: The unique region of the VP1 capsid protein of adeno-associated viruses (AAV) in common with autonomously replicating parvoviruses comprises a secreted phospholipase A2 (sPLA2) homology domain. While the sPLA2 domain of Minute Virus of Mice has recently been shown to mediate endosomal escape by lipolytic pore formation, experimental evidence for a similar function in AAV infection is still lacking. Here, we explored the function of the sPLA2 domain of AAV by making use of the serotype 2 mutant 76HD/AN. The sPLA2 defect in 76HD/AN, which severely impairs AAV''s infectivity, could be complemented in trans by co-infection with wild-type AAV2. Furthermore, co-infection with endosomolytically active, but not with inactive adenoviral variants partially rescued 76HD/AN, providing the first evidence for a function of this domain in endosomal escape of incoming AAV particles. [Copyright &y& Elsevier]

It still remains controversial whether simple obesity, as measured by the body mass index (BMI), is an independent risk factor for Barrett's esophagus (BE). Recent studies have shown abdominal obesity, as defined by the waist circumference (WC) and the waist-to-hip ratio (WHR), to be a risk factor for BE, independent of the BMI, with the association between BMI and BE being no longer observed after adjustment for the WC and WHR. Moreover, visceral obesity, as directly measured by the surface area of the visceral adipose tissue (VAT) on abdominal CT images, has also been reported to have an association with the risk of BE. In addition to the mechanical effects of abdominal obesity, that is, increase of the intra- abdominal pressure by the large amount of adipose tissue, circulating factors secreted from the VAT, such as tumor necrosis factor-α, interleukin-6, leptin, and adiponectin, have also been proposed to be pathogenetically linked to BE and esophageal adenocarcinoma. Obesity is associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal obesity, especially visceral obesity. This raises several questions regarding the pathogenesis of obesity-related BE. Larger studies with prospective enrollment of patients are required for further examination of this issue. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]