Function In Obesity Research Articles

Regulation of Lymphatic Function in Obesity.

The lymphatic system has many functions, including macromolecules transport, fat absorption, regulation and modulation of adaptive immune responses, clearance of inflammatory cytokines, and cholesterol metabolism. Thus, it is evident that lymphatic function can play a key role in the regulation of a wide array of biologic phenomenon, and that physiologic changes that alter lymphatic function may have profound pathologic effects. Recent studies have shown that obesity can markedly impair lymphatic function. Obesity-induced pathologic changes in the lymphatic system result, at least in part, from the accumulation of inflammatory cells around lymphatic vessel leading to impaired lymphatic collecting vessel pumping capacity, leaky initial and collecting lymphatics, alterations in lymphatic endothelial cell (LEC) gene expression, and degradation of junctional proteins. These changes are important since impaired lymphatic function in obesity may contribute to the pathology of obesity in other organ systems in a feed-forward manner by increasing low-grade tissue inflammation and the accumulation of inflammatory cytokines. More importantly, recent studies have suggested that interventions that inhibit inflammatory responses, either pharmacologically or by lifestyle modifications such as aerobic exercise and weight loss, improve lymphatic function and metabolic parameters in obese mice. The purpose of this review is to summarize the pathologic effects of obesity on the lymphatic system, the cellular mechanisms that regulate these responses, the effects of impaired lymphatic function on metabolic syndrome in obesity, and the interventions that may improve lymphatic function in obesity.

Abstract #787708: Identification of FABP4 (AP2) as an Adipo-Pulmonary Regulator of Airway Function in Obesity Related Asthma

Abstract #787708: Identification of FABP4 (AP2) as an Adipo-Pulmonary Regulator of Airway Function in Obesity Related Asthma

The role of comorbidity in the association of obesity with unemployment and disability

PurposeThe association of obesity with a large range of physical conditions and numerous psychiatric disorders has been extensively studied. Our study sought the extent to which physical conditions or psychiatric disorders associated with obesity mediate the association of obesity with unemployment or disability. MethodsUsing data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III, 2012–2013), we estimated the prevalence of unemployment as a function of obesity taking into account these comorbidities. Data on self-reported height and weight were available for 35,725 respondents. Clinician-diagnosed physical conditions were self-reported and lifetime psychiatric disorders were assessed with a semistructured interview. ResultsThe adjusted prevalence of obesity was 30.4%. Participants with obesity were more likely than participants without obesity to report at least one of the 31 assessed physical conditions (64.46% vs. 46.87%; P < .001). Participants with obesity were more likely to report at least one of the 24 assessed psychiatric diagnoses than respondents without obesity (60.57 vs. 56.75%; P < .001). The rates of unemployment were higher in participants with obesity than in those without obesity (15.75% vs. 11.26%; P < .001). Similarly, participants with obesity reported higher rates of disability than those without obesity. Although the number of physical conditions and psychiatric disorders partly explains this association, obesity remained significantly associated with unemployment and greater disability when controlling for the number of physical conditions and psychiatric disorders. ConclusionsObesity is associated with high rates of unemployment and with high disability. This is not explained solely by the high rate of physical conditions and psychiatric disorders associated with obesity.

Immune regulation of islet homeostasis and adaptation.

The islet of Langerhans produces endocrine hormones to regulate glucose homeostasis. The normal function of the islet relies on the homeostatic regulations of cellular composition and cell–cell interactions within the islet microenvironment. Immune cells populate the islet during embryonic development and participate in islet organogenesis and function. In obesity, a low-grade inflammation manifests in multiple organs, including pancreatic islets. Obesity-associated islet inflammation is evident in both animal models and humans, characterized by the accumulation of immune cells and elevated production of inflammatory cytokines/chemokines and metabolic mediators. Myeloid lineage cells (monocytes and macrophages) are the dominant types of immune cells in islet inflammation during the development of obesity and type 2 diabetes mellitus (T2DM). In this review, we will discuss the role of the immune system in islet homeostasis and inflammation and summarize recent findings of the cellular and molecular factors that alter islet microenvironment and β cell function in obesity and T2DM.

Novel roles of PFKFB3 in mediating endothelial dysfunction in obesity

Obesity is a major and growing health problem in the US with over 93 million afflicted. Although, obesity itself is not considered a disease, it is a strong risk factor for cardiovascular disease, in large part due to an altered metabolic state. The relationship between metabolic dysfunction and impaired cardiovascular health remain incompletely understood.One of the earliest consequences of cardiovascular dysfunction in obesity is the loss of endothelial function and impaired nitric oxide (NO) signaling. NO is best known as the mediator of endothelium‐dependent relaxation, but it is also vital for maintaining blood vessel homeostasis through inhibition of leukocyte adhesion and smooth muscle cell proliferation. In blood vessels, NO is synthesized by endothelial nitric oxide synthase (eNOS) and dysregulation of eNOS has been shown to occur through changes in its expression and post‐translational phosphorylation. The biological actions of NO can be further compromised by rapid inactivation by reactive oxygen species (ROS) such as superoxide that are generated by NADPH oxidases (NOX) as well as numerous other enzyme systems.Our laboratory has previously shown that an imbalance between NO and superoxide‐generating pathways is responsible for the loss of endothelial function in obesity. However, the signals coordinating the loss of NO and increased superoxide with altered metabolism remain poorly defined.In our studies we have found that expression of the glycolytic enzyme 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3) is significantly increased in endothelial cells from obese animals. PFKFB3 is responsible for fructose‐2,6‐bisphosphate generation in vascular cells which is a potent allosteric activator of phosphofructokinase‐1 (PFK‐1), one of the rate‐limiting enzymes of glycolysis. We have also found that adenovirus‐mediated expression of PFKFB3 within the endothelium of mouse blood vessels is accompanied by the loss of endothelium‐dependent relaxation.In addition to its effects on blood vessels, overexpression of PFKFB3 in cultured cells resulted in decreased NO production as a result of increased eNOS phosphorylation on the well‐known inhibitory PKC phosphorylation site, threonine 495 (T495). Furthermore, PFKFB3 overexpression blunted Akt‐S473 phosphorylation, reducing stimulus‐dependent phosphorylation of eNOS at S1177. In addition to its negative effect on NO signaling overexpression of PFKFB3 increased the activity and mRNA level of NOX1, a major contributor to endothelial dysfunction in obesity.These results demonstrate a novel functional relationship between endothelial cell metabolism, nitric oxide and ROS production that may contribute to endothelial dysfunction in obesity.Support or Funding Information1R01HL147159‐01

Subpopulation-specific differences in skeletal muscle mitochondria in humans with obesity: insights from studies employing acute nutritional and exercise stimuli.

Mitochondria from skeletal muscle of humans with obesity often display alterations with respect to their morphology, proteome, biogenesis, and function. These changes in muscle mitochondria are considered to contribute to metabolic abnormalities observed in humans with obesity. Most of the evidence describing alterations in muscle mitochondria in humans with obesity, however, lacks reference to a specific subcellular location. This is despite data over the years showing differences in the morphology and function of subsarcolemmal (found near the plasma membrane) and intermyofibrillar (nested between the myofibrils) mitochondria in skeletal muscle. Recent studies reveal that impairments in mitochondrial function in obesity with respect to the subcellular location of the mitochondria in muscle are more readily evident following exposure of the skeletal muscle to physiological stimuli. In this review, we highlight the need to understand skeletal muscle mitochondria metabolism in obesity in a subpopulation-specific manner and in the presence of physiological stimuli that modify mitochondrial function in vivo. Experimental approaches employed under these conditions will allow for more precise characterization of impairments in skeletal muscle mitochondria and their implications in inducing metabolic dysfunction in human obesity.

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity.

Obesity is associated with the development of metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. The presence of chronic, low-grade inflammation appears to be an important mechanistic link between excess nutrients and clinical disease. The onset of these metabolic disorders coincides with changes in the number and phenotype of macrophages in peripheral organs, particularly in the liver and adipose tissue. Macrophage accumulation in these tissues has been implicated in tissue inflammation and fibrosis, contributing to metabolic disease progression. Recently, the concept has emerged that changes in macrophage metabolism affects their functional phenotype, possibly triggered by distinct environmental metabolic cues. This may be of particular importance in the setting of obesity, where both liver and adipose tissue are faced with a high metabolic burden. In the first part of this review we will discuss current knowledge regarding macrophage dynamics in both adipose tissue and liver in obesity. Then in the second part, we will highlight data linking macrophage metabolism to functional phenotype with an emphasis on macrophage activation in metabolic disease. The importance of understanding how tissue niche influences macrophage function in obesity will be highlighted. In addition, we will identify important knowledge gaps and outstanding questions that are relevant for future research in this area and will facilitate the identification of novel targets for therapeutic intervention in associated metabolic diseases.

Adipocyte Specific HO-1 Gene Therapy is Effective in Antioxidant Treatment of Insulin Resistance and Vascular Function in an Obese Mice Model.

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity.

Targeting Leukotrienes as a Therapeutic Strategy to Prevent Comorbidities Associated with Metabolic Stress.

Leukotrienes (LTs) are potent lipid mediators that exert a variety of functions, ranging from maintaining the tone of the homeostatic immune response to exerting potent proinflammatory effects. Therefore,LTs are essential elements in the development and maintenance of different chronic diseases, such as asthma, arthritis, and atherosclerosis. Due to the pleiotropic effects of LTs in the pathogenesis of inflammatory diseases, studies are needed to discover potent and specific LT synthesis inhibitors and LT receptor antagonists. Even though most clinical trials using LT inhibitors or antagonists have failed due to low efficacy and/or toxicity, new drug development strategies are driving the discovery for LT inhibitors to prevent inflammatory diseases. A newly important detrimental role for LTs in comorbidities associated with metabolic stress has emerged in the last few years and managing LT production and/or actions could represent an exciting new strategy to prevent or treat inflammatory diseases associated with metabolic disorders. This review is intended to shed light on the synthesis and actions of leukotrienes, the most common drugs used in clinical trials, and discuss the therapeutic potential of preventing LT function in obesity, diabetes, and hyperlipidemia.

Male health and obesity – diagnostic and therapeutic approach

Obesity may present as a significant medical problem for any person, regardless of age or gender. In men obesity causes considerable psychological stress, sexual dysfunction, subfertility, hypogonadism and cardiovascular conditions. These problems may form numerous pathological associations between each other, creating a vicious circle. The main factors which influence male fertility and sexual function in obesity and metabolic syndrome are imbalance of sex hormones and systemic inflammation. In many patients symptomatic treatment is necessary for above-mentioned manifestations, but it is always rational to act on their pathophysiology and to recommend to lower the body mass by diet and lifestyle modification. When it proves impossible for the patient to follow such recommendations and when behavioral approach fails, central-acting and peripheral-acting medications may be used, including orlistat, sibutramine and liraglutide. Bariatric surgery should be offered to patients with high body mass index in whom conservative management fails. Without elimination of excess body mass it is difficult to solve problems regarding sexual dysfunction, hypogonadism and subfertility in obese males. All these issues and available modes of pharmacological treatment are described in this review.

Epigenetic and Transcriptomic Characterization of Pure Adipocyte Fractions From Obese Pigs Identifies Candidate Pathways Controlling Metabolism

Reprogramming of adipocyte function in obesity is implicated in metabolic disorders like type 2 diabetes. Here, we used the pig, an animal model sharing many physiological and pathophysiological similarities with humans, to perform in-depth epigenomic and transcriptomic characterization of pure adipocyte fractions. Using a combined DNA methylation capture sequencing and Reduced Representation bisulfite sequencing (RRBS) strategy in 11 lean and 12 obese pigs, we identified in 3529 differentially methylated regions (DMRs) located at close proximity to-, or within genes in the adipocytes. By sequencing of the transcriptome from the same fraction of isolated adipocytes, we identified 276 differentially expressed transcripts with at least one or more DMR. These transcripts were over-represented in gene pathways related to MAPK, metabolic and insulin signaling. Using a candidate gene approach, we further characterized 13 genes potentially regulated by DNA methylation and identified putative transcription factor binding sites that could be affected by the differential methylation in obesity. Our data constitute a valuable resource for further investigations aiming to delineate the epigenetic etiology of metabolic disorders.

Effects of Protective Mechanical Ventilation With Different PEEP Levels on Alveolar Damage and Inflammation in a Model of Open Abdominal Surgery: A Randomized Study in Obese Versus Non-obese Rats.

Intraoperative positive end-expiratory pressure (PEEP) has been proposed to restore lung volumes and improve respiratory function in obesity. However, the biological impact of different PEEP levels on the lungs in obesity remains unknown. We aimed to compare the effects of PEEP = 2 cmH2O versus PEEP = 6 cmH2O during ventilation with low tidal volumes on lung function, histology, and biological markers in obese and non-obese rats undergoing open abdominal surgery. Forty-two Wistar rats (21 obese, 21 non-obese) were anesthetized and tracheotomized, and laparotomy was performed with standardized bowel manipulation. Rats were randomly ventilated with protective tidal volume (7 ml/kg) at PEEP = 2 cmH2O or PEEP = 6 cmH2O for 4 h, after which they were euthanized. Lung mechanics and histology, alveolar epithelial cell integrity, and biological markers associated with pulmonary inflammation, alveolar stretch, extracellular matrix, and epithelial and endothelial cell damage were analyzed. In obese rats, PEEP = 6 cmH2O compared with PEEP = 2 cmH2O was associated with less alveolar collapse (p = 0.02). E-cadherin expression was not different between the two PEEP groups. Gene expressions of interleukin (IL)-6 (p = 0.01) and type III procollagen (p = 0.004), as well as protein levels of tumor necrosis factor-alpha (p = 0.016), were lower at PEEP = 6 cmH2O than at PEEP = 2 cmH2O. In non-obese animals, PEEP = 6 cmH2O compared with PEEP = 2 cmH2O led to increased hyperinflation, reduced e-cadherin (p = 0.04), and increased gene expression of IL-6 (p = 0.004) and protein levels of tumor necrosis factor-alpha (p-0.029), but no changes in fibrogenesis. In conclusion, PEEP = 6 cmH2O reduced lung damage and inflammation in an experimental model of mechanical ventilation for open abdominal surgery, but only in obese animals.

A Human 3D Extracellular Matrix-Adipocyte Culture Model for Studying Matrix-Cell Metabolic Crosstalk.

The extracellular matrix (ECM) plays a central role in regulating tissue homeostasis, engaging in crosstalk with cells and regulating multiple aspects of cellular function. The ECM plays a particularly important role in adipose tissue function in obesity, and alterations in adipose tissue ECM deposition and composition are associated with metabolic disease in mice and humans. Tractable in vitro models that permit dissection of the roles of the ECM and cells in contributing to global tissue phenotype are sparse. We describe a novel 3D in vitro model of human ECM-adipocyte culture that permits study of the specific roles of the ECM and adipocytes in regulating adipose tissue metabolic phenotype. Human adipose tissue is decellularized to isolate ECM, which is subsequently repopulated with preadipocytes that are then differentiated within the ECM into mature adipocytes. This method creates ECM-adipocyte constructs that are metabolically active and retain characteristics of the tissues and patients from which they are derived. We have used this system to demonstrate disease-specific ECM-adipocyte crosstalk in human adipose tissue. This culture model provides a tool for dissecting the roles of the ECM and adipocytes in contributing to global adipose tissue metabolic phenotype and permits study of the role of the ECM in regulating adipose tissue homeostasis.

Experimental Approach to Examine Leptin Signaling in the Carotid Bodies and its Effects on Control of Breathing.

An adipocyte-produced hormone leptin is a potent respiratory stimulant, which may play an important role in defending respiratory function in obesity. The carotid bodies (CB), a key organ of peripheral hypoxic sensitivity, express the long functional isoform of leptin receptor (LepRb) but the role of leptin signaling in control of breathing has not been fully elucidated. We examined the hypoxic ventilatory response (HVR) (1) in C57BL/6J mice before and after leptin infusion at baseline and after CB denervation; (2) in LepRb-deficient obese db/db mice at baseline and after LepRb overexpression in CBs. In C57BL/6J mice, leptin increased HVR and effects of leptin on HVR were abolished by CB denervation. In db/db mice, LepRb expression in CB augmented the HVR. Therefore, we conclude that leptin acts in CB to augment responses to hypoxia.

Liraglutide improves vascular dysfunction by regulating a cAMP-independent PKA-AMPK pathway in perivascular adipose tissue in obese mice

BackgroundPerivascular adipose tissue (PVAT) attenuates its anti-contractile effect through an endothelial-dependent mechanism that aggravates endothelial dysfunction in obesity. The present study was conducted to explore whether liraglutide could improve vascular dysfunction, including the anti-contractile effect of PVAT and endothelial function, by modulating PVAT-related signaling pathways in obesity. MethodsC57BL/6 mice were fed a normal-chow diet or a high-fat diet (HFD) with or without liraglutide treatment. Vascular function of the thoracic aorta with or without PVAT were measured. Protein levels of components of the PKA-AMPK-PGC1α and antioxidant signaling pathway in PVAT were determined by western blotting. Brown adipose tissue-related gene in PVAT was measured by qRT-PCR. ResultsMetabolic profiles of HFD-fed mice were improved after treatment with liraglutide. Liraglutide improved PVAT-induced anti-contractile capability and PVAT-induced endothelial dysfunction in HFD-fed mice both in vivo and ex vivo. However, blocking PKA, or AMPK, but not cAMP, attenuated these beneficial effects of liraglutide. Treating HFD-fed mice with liraglutide activated the AMPK/eNOS pathway and induced browning-related gene expression. Moreover, liraglutide increased antioxidant capability. The protective effects were related to activation of a cAMP-independent PKA-AMPK pathway, as demonstrated by western blot and PCR. ConclusionsLiraglutide improved vascular dysfunction by modulating a cAMP-independent PKA-AMPK pathway in PVAT in HFD-induced obese mice. The findings provide a novel mechanism for the cardiovascular protection of liraglutide by modulating PVAT function in obesity.

P735Interleukin-33 induced eosinophilia restores perivascular adipose tissue function in obesity

Abstract Background/Purpose Perivascular adipose tissue (PVAT) is essential in the modulation of vascular tone. Recently we have shown that resident eosinophils play a vital role in regulating PVAT function. In obesity, eosinophil numbers are reduced and PVAT anticontractile function is lost, resulting in increased vascular tone, which will contribute to development of hypertension and type-2 diabetes. Evidence suggests that eosinophilia resulting from parasitic infection may be useful in improving glucose tolerance; therefore, we investigated the effects of eosinophilia on PVAT function in health and obesity. Methods Control mice and a high fat fed mouse model of obesity were administered intraperitoneal injections of interleukin-33 (IL-33, 0.1μg) over a five day period. Blood pressure, blood glucose and plasma insulin were measured and compared with un-injected control and obese mice. Wire myography was used to assess the vascular contractility of mesenteric arteries (&lt;250μm, +/− PVAT) from both injected and un-injected control and obese mice in response to noradrenaline. ELISAs and immunohistochemistry were used to examine eosinophil numbers. Results High fat feeding induced significant elevations in blood pressure, blood glucose and plasma insulin, which were reduced using IL-33 injections. Eosinophilia was confirmed in blood plasma using an eosinophil cationic protein ELISA. Using wire myography, mesenteric arteries from control mice PVAT exerted an anticontractile effect on the vessels, which was enhanced in control mice injected with IL-33. In obese mice, the PVAT anticontractile effect was lost, but was restored in IL-33 injected obese mice. Using immunohistochemistry, we confirm that eosinophils numbers in PVAT were reduced in obesity and increased in IL-33 treated PVAT. Conclusions IL-33 injections induced eosinophilia in both control and obese mice. IL-33 treatment restored PVAT function in obesity, and enhanced the anticontractile function of PVAT in healthy animals. In addition, only five consecutive injections of IL-33 reversed development of hypertension and type-2 diabetes in obese mice. These data suggest that IL-33 induced eosinophilia presents a novel approach to treatment of hypertension and type-2 diabetes in obesity. Acknowledgement/Funding British Heart Foundation

Effects of glucagon-like peptide-1 analog liraglutide on the systemic inflammation in high-fat-diet-induced mice

Metabolic syndrome is a chronic-metabolic disease caused by a variety of factors, including high peripheral blood insulin levels and insulin resistance. It has been reported that GLP-1 could regulate insulin resistance. It is not known whether and how GLP-1 protects from fat-induced inflammation and immune changes. We investigated if GLP-1 alters the populations of fat-induced inflammation and immune cells and the related mechanism. We obtained obese C57BL/6J mice by feeding them high-fat food, then treated the obese mice with GLP-1+ high-fat diet (G + Hi), normal chow diet (Nor), or high-fat diet (Hi) (n = 20 for each group) for 8 weeks. The GLP-1 receptor-/- B6 group were fed with HFD for 8 weeks (GLP-1R KO + Hi). In vivo and in vitro experiments were conducted on mice immune cells to investigate the effects of GLP-1 on the changes of the immune components and functions in obesity. We found that GLP-1 could efficiently change the CD4+ T subsets and level of cytokines in high-fat-induced mice by GLP-1 receptor. Further, these changes were correlated with a reduction in fat content and serum lipid level. Interestingly, GLP-1 could enhance the function of Tregs in vitro. Our data showed that GLP-1 has an important role in shaping the CD4+ T population in high-fat-diet-induced mice by GLP-1 receptor, possibly providing a new target for the treatment of metabolic syndrome.

Calcification biomarkers and vascular dysfunction in obesity and type 2 diabetes: influence of oral hypoglycemic agents.

Vascular aging in obesity and type 2 diabetes (T2D) is associated with progressive vascular calcification, an independent predictor of morbidity and mortality. Pathways for vascular calcification modulate bone matrix deposition, thus regulating calcium deposits. We investigated the association between biomarkers of vascular calcification and vasodilator function in obesity or T2D, and whether antidiabetic therapies favorably impact those markers. Circulating levels of proteins involved in vascular calcification, such as osteopontin (OPN), osteoprotegerin (OPG), regulated on activation, normal T cell expressed and secreted (RANTES), and fetuin-A were measured in lean subjects, individuals with metabolically healthy obesity (MHO), and patients with metabolically unhealthy obesity (MUO) or T2D. Vasodilator function was assessed by infusion of ACh and sodium nitroprusside (SNP). Circulating levels of OPN were higher in the MUO/T2D group than in lean subjects (P < 0.05); OPG and RANTES were higher in MUO/T2D group than in the other groups (both P < 0.001); fetuin-A was not different between groups (P > 0.05); vasodilator responses to either ACh or SNP were impaired in both MUO/T2D and MHO compared with lean subjects (all P < 0.001). In patients with T2D who were enrolled in the intervention trial, antidiabetic treatment with glyburide, metformin, or pioglitazone resulted in a significant reduction of circulating OPG (P = 0.001), without changes in the other biomarkers and vasodilator responses (all P > 0.05). In conclusion, obese patients with MUO/T2D have elevated circulating OPN, OPG, and RANTES; in these patients, antidiabetic treatment reduces only circulating OPG. Further study is needed to better understand the mechanisms of vascular calcifications in obesity and diabetes.

A gene expression network analysis of the pancreatic islets from lean and obese mice identifies complement 1q\xa0like-3 secreted protein as a regulator of \u03b2-cell function

Secreted proteins are important metabolic regulators. Identifying and characterizing the role of secreted proteins from small tissue depots such as islets of Langerhans, which are required for the proper control of whole-body energy metabolism, remains challenging. Our objective was to identify islet-derived secreted proteins that affect islet function in obesity. Lean and obese mouse islet expression data were analyzed by weighted gene co-expression network analysis (WGCNA) to identify trait-associated modules. Subsequently, genes within these modules were filtered for transcripts that encode for secreted proteins based on intramodular connectivity, module membership, and differential expression. Complement 1q like-3 (C1ql3) secreted protein was identified as a hub gene affecting islet function in obesity. Co-expression network, hierarchal clustering, and gene-ontology based approaches identified a putative role for C1ql3 in regulating β-cell insulin secretion. Biological validation shows that C1ql3 is expressed in β-cells, it inhibits insulin secretion and key genes that are involved in β-cell function. Moreover, the increased expression of C1ql3 is correlated with the reduced insulin secretion in islets of obese mice. Herein, we demonstrate a streamlined approach to effectively screen and determine the function of secreted proteins in islets, and identified C1ql3 as a putative contributor to reduced insulin secretion in obesity, linking C1ql3 to an increased susceptibility to type 2 diabetes.

Pulmonary Function in Obese individuals

This review tries to discuss the researches that are related to pulmonary function in obesity, its mechanisms and consequences. Abdominal adiposity could be considered as a better predictor of pulmonary function than weight or BMI. Obesity has important effects on respiratory function, which add considerably to the load of respiratory disease. Weigh loss is found to improve lung function in patients with respiratory disorders especially with asthma.