Project description:To assess the phospholipase activity of endothelial (EL) and hepatic lipase (HL) in postheparin plasma of subjects with metabolic syndrome (MS)/obesity and their relationship with atherogenic and antiatherogenic lipoproteins. Additionally, to evaluate lipoprotein lipase (LPL) and HL activity as triglyceride (TG)-hydrolyses to complete the analyses of SN1 lipolytic enzymes in the same patient.Plasma EL, HL, and LPL activities were evaluated in 59 patients with MS and 36 controls. A trend toward higher EL activity was observed in MS. EL activity was increased in obese compared with normal weight group (P=0.009) and was negatively associated with high-density lipoprotein-cholesterol (P=0.014 and P=0.005) and apolipoprotein A-I (P=0.045 and P=0.001) in control and MS group, respectively. HL activity, as TG-hydrolase, was increased in MS (P=0.025) as well as in obese group (P=0.017); directly correlated with low-density lipoprotein-cholesterol (P=0.005) and apolipoprotein B (P=0.003) and negatively with high-density lipoprotein-cholesterol (P=0.021) in control group. LPL was decreased in MS (P<0.001) as well as in overweight and obese compared with normal weight group (P=0.015 and P=0.004, respectively); inversely correlated %TG-very low-density lipoproteins (P=0.04) and TG/apolipoprotein B index (P=0.013) in control group. These associations were not found in MS.We describe for the first time EL and HL activity as phospholipases in MS/obesity, being both responsible for high-density lipoprotein catabolism. Our results elucidate part of the remaining controversies about SN1 lipases activity in MS and different grades of obesity. The impact of insulin resistance on the activity of the 3 enzymes determines the lipoprotein alterations observed in these states.
Project description:METABOLIC SYNDROME IS A CLUSTER OF METABOLIC ABNORMALITIES AND IS DEFINED AS THE PRESENCE OF THREE OR MORE OF THE FOLLOWING FACTORS: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose. Obesity, which is accompanied by metabolic dysregulation often manifested in the metabolic syndrome, is an established risk factor for many cancers. Adipose tissue, particularly visceral fat, is an important metabolic tissue as it secretes systemic factors that alter the immunologic, metabolic, and endocrine milieu and also promotes insulin resistance. Within the growth-promoting, proinflammatory environment of the obese state, cross-talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, adipocytokines, and other mediators that may enhance cancer risk and progression. This paper synthesizes the evidence on key molecular mechanisms underlying the obesity-cancer link.
Project description:BackgroundOverweight and obesity are known to impact male fertility and are commonly associated with abdominal obesity and metabolic disorders. The association between abdominal obesity or metabolic syndrome with male reproduction has not been fully investigated. Moreover, many factors may interfere with the evaluation of the impact of metabolic syndrome on male fertility. Thus, tobacco is known to alter the spermatic parameters and phenomena linking smoking with metabolic syndrome are therefore complex. The main objective of this study has been to investigate the potential association of metabolic syndrome with male idiopathic infertility given smoking status.Materiel and methodsThe data of this study concerned infertile (n = 96) and fertile (n = 100) men under 45 years of age who have been recruited in the ALIFERT case-control study. Body mass index and waist circumference were measured. Serum triglycerides, cholesterol (total, high density lipoprotein, and low density lipoprotein cholesterol) and fasting blood glucose were assayed. Metabolic syndrome has been diagnosed in the presence of at least three of the following criteria: increased waist circumference, high triglycerides, fasting glucose or arterial blood pressure and low high density lipoprotein cholesterol.ResultsThe present study reports that infertile men are in poorer health condition compared to fertile men and are more often smokers. The results of this study suggested metabolic syndrome and smoking to be independent risk factor for idiopathic infertility.ConclusionsMetabolic syndrome and smoking should systematically be checked at the beginning of medical care in infertile males and personal and multifaceted coaching should be proposed to deal jointly with smoking and metabolic disorders.Trial registrationNCT01093378 ALIFERT. Registered: March 25, 2010.
Project description:Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.
Project description:Bile acids are increasingly recognized as key regulators of systemic metabolism. While bile acids have long been known to play important and direct roles in nutrient absorption, bile acids also serve as signalling molecules. Bile acid interactions with the nuclear hormone receptor farnesoid X receptor (FXR) and the membrane receptor G-protein-coupled bile acid receptor 5 (TGR5) can regulate incretin hormone and fibroblast growth factor 19 (FGF19) secretion, cholesterol metabolism, and systemic energy expenditure. Bile acid levels and distribution are altered in type 2 diabetes and increased following bariatric procedures, in parallel with reduced body weight and improved insulin sensitivity and glycaemic control. Thus, modulation of bile acid levels and signalling, using bile acid binding resins, TGR5 agonists, and FXR agonists, may serve as a potent therapeutic approach for the treatment of obesity, type 2 diabetes, and other components of the metabolic syndrome in humans.
Project description:The G-protein beta subunit 3 (GNB3) gene has been implicated in obesity risk; however, the molecular mechanism of GNB3-related disease is unknown. GNB3 duplication is responsible for a syndromic form of childhood obesity, and an activating DNA sequence variant (C825T) in GNB3 is also associated with obesity. To test the hypothesis that GNB3 overexpression causes obesity, we created bacterial artificial chromosome (BAC) transgenic mice that carry an extra copy of the human GNB3 risk allele. Here we show that GNB3-T/+ mice have increased adiposity, but not greater food intake or a defect in satiety. GNB3-T/+ mice have elevated fasting plasma glucose, insulin, and C-peptide, as well as glucose intolerance, indicating type 2 diabetes. Fasting plasma leptin, triglycerides, cholesterol and phospholipids are elevated, suggesting metabolic syndrome. Based on a battery of behavioral tests, GNB3-T/+ mice did not exhibit anxiety- or depressive-like phenotypes. GNB3-T/+ and wild-type animals have similar activity levels and heat production; however, GNB3-T/+ mice exhibit dysregulation of acute thermogenesis. Finally, Ucp1 expression is significantly lower in white adipose tissue (WAT) in GNB3-T/+ mice, suggestive of WAT remodeling that could lead to impaired cellular thermogenesis. Taken together, our study provides the first functional link between GNB3 and obesity, and presents insight into novel pathways that could be applied to combat obesity and type 2 diabetes.
Project description:Dragonflies infected with noninvasive gregarine gut parasites (Apicomplexa: Eugregarinorida) [corrected] have reduced flight-muscle performance, an inability to metabolize lipid in their muscles, twofold-elevated hemolymph carbohydrate concentrations, and they accumulate fat in their thorax in a manner analogous to mammalian obesity. Gregarine infection is associated with inappropriate responses of hemolymph carbohydrate concentration to insulin and with chronic activation in the flight muscles of p38 MAP kinase, a signaling molecule involved in immune and stress responses. Short-term exposure to gregarine excretory/secretory products caused elevated blood carbohydrate and p38 MAPK activation in healthy individuals. These characteristics comprise a set of symptoms and processes that are known in mammals as metabolic syndrome but which have not previously been described in other animal taxa. In addition to expanding the known taxonomic breadth of metabolic disease, these results indicate that insects may be useful experimental models for studying its underlying biology and mechanisms.
Project description:BackgroundCancer related infertility can have an impact on couple relationships, with evidence that couple communication facilitates coping. However, little is known about the ways in which couples communicate about cancer-related fertility concerns. The aim of this article is to examine couple communication about fertility concerns in the context of cancer, and the perceived quality of such communication from the perspective of cancer survivors and their partners.MethodsEight-hundred and seventy-eight cancer survivors (693 women, 185 men) and 144 partners (82 women, 62 men), across a range of tumour types and age groups, completed a survey which examined cancer related fertility concerns. Seventy-eight survivors (61 women and 17 men), and 26 partners (13 women and 13 men), participated in semi-structured interviews, in order to examine the subjective experience of fertility concerns in-depth. Thematic analysis was used to analyse the interviews and open ended survey questions. Valid percentages for single items from the relationships subscale of the Fertility Preservation Inventory (FPI) related to qualitative themes, identified frequency of responses.ResultsThe major theme was 'talking but not always understanding". 89.6% of cancer survivors and partners (95.1%) reported working well together handling fertility questions (FPI), but agreed that communication could be improved (65.9% survivors; 65% partners). Open and honest couple communication was associated with feelings of support, understanding and relationship growth, including perception of partner comfort (79.2% survivors, 81.6% partners). However, 32% survivors and 31.1% partners concealed fertility concerns to avoid upsetting their partner, or reported that their partner doesn't understand their fertility concerns (survivors 25.5%, partners 14.6%), with 14.1% of cancer survivors and 19.4% partners reporting fear of relationship breakdown because of fertility issues. Fear of rejection when forming new relationships, and concerns about how to talk to future partners, was reported by non-partnered individuals.ConclusionHealth-care professionals should include partners of cancer survivors in fertility discussions. Couple interventions developed in general psycho-oncology should be extended to the domain of fertility, in order to facilitate effective couple communication. Communication in future relationships needs to be addressed for single people and adolescents and young adults (AYAs) who have fertility concerns.
Project description:Metabolic syndrome (MS) is a cluster of risk factors that can lead to a disorder of energy utilization and storage and raises risk for heart disease and other health problems. Obesity is a prevalent metabolic disorder in the developed countries and in large parts of developing world that is one of main features of being diagnosed as MS. However, only part of obese people will develop into MS. Therefore, it is worthwhile to search more biomarkers implicated in metabolic syndrome that can help understanding the complex pathogenetic process of this disease better. In this study, we have performed a human serum proteomic analysis of MS using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry.