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https://www.readbyqxmd.com/read/29775936/from-hit-to-lead-structure-based-discovery-of-naphthalene-1-sulfonamide-derivatives-as-potent-and-selective-inhibitors-of-fatty-acid-binding-protein-4
#1
Ding-Ding Gao, Hui-Xia Dou, Hai-Xia Su, Ming-Ming Zhang, Ting Wang, Qiu-Feng Liu, Hai-Yan Cai, Hai-Peng Ding, Zhuo Yang, Wei-Liang Zhu, Ye-Chun Xu, He-Yao Wang, Ying-Xia Li
Fatty acid binding protein 4 (FABP4) plays a critical role in metabolism and inflammatory processes and therefore is a potential therapeutic target for immunometabolic diseases such as diabetes and atherosclerosis. Herein, we reported the identification of naphthalene-1-sulfonamide derivatives as novel, potent and selective FABP4 inhibitors by applying a structure-based design strategy. The binding affinities of compounds 16dk, 16do and 16du to FABP4, at the molecular level, are equivalent to or even better than that of BMS309403...
May 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29775748/microrna-204-5p-regulates-3t3-l1-preadipocyte-proliferation-apoptosis-and-differentiation
#2
Jingjing Du, Peiwen Zhang, Mailin Gan, Xue Zhao, Yan Xu, Qiang Li, Yanzhi Jiang, Guoqing Tang, Mingzhou Li, Jinyong Wang, Xuewei Li, Shunhua Zhang, Li Zhu
Obesity due to excessive lipid accumulation is closely associated with metabolic diseases such as type 2 diabetes, insulin resistance and inflammation. Therefore, a detailed understanding of the molecular mechanisms that underlie adipogenesis is crucial to develop treatments for diseases related to obesity. Here, we found that the microRNA-204-5p (miR-204-5p) was expressed at low levels in fat tissues from obese mice fed long-term with a high-fat diet (HFD). Overexpression or inhibition of miR-204-5p in vitro in 3T3-L1 preadipocytes significantly inhibited or promoted 3T3-L1 proliferation, respectively, an effect mediated by regulating cell proliferation factors...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775456/maternal-obesogenic-diet-induces-endometrial-hyperplasia-an-early-hallmark-of-endometrial-cancer-in-a-diethylstilbestrol-mouse-model
#3
Theresa O Owuor, Michaela Reid, Lauren Reschke, Ian Hagemann, Suellen Greco, Zeel Modi, Kelle H Moley
Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain...
2018: PloS One
https://www.readbyqxmd.com/read/29773464/sex-and-gender-differences-in-developmental-programming-of-metabolism
#4
REVIEW
Laura Dearden, Sebastien G Bouret, Susan E Ozanne
BACKGROUND: The early life environment experienced by an individual in utero and during the neonatal period is a major factor in shaping later life disease risk-including susceptibility to develop obesity, diabetes, and cardiovascular disease. The incidence of metabolic disease is different between males and females. How the early life environment may underlie these sex differences is an area of active investigation. SCOPE OF REVIEW: The purpose of this review is to summarize our current understanding of how the early life environment influences metabolic disease risk in a sex specific manner...
April 30, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29772784/capsaicin-in-metabolic-syndrome
#5
REVIEW
Sunil K Panchal, Edward Bliss, Lindsay Brown
Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders...
May 17, 2018: Nutrients
https://www.readbyqxmd.com/read/29772682/the-association-of-dietary-fiber-intake-with-cardiometabolic-risk-in-four-countries-across-the-epidemiologic-transition
#6
Louise Lie, Laquita Brown, Terrence E Forrester, Jacob Plange-Rhule, Pascal Bovet, Estelle V Lambert, Brian T Layden, Amy Luke, Lara R Dugas
The greatest burden of cardiovascular disease is now carried by developing countries with cardiometabolic conditions such as metabolic syndrome, obesity and inflammation believed to be the driving force behind this epidemic. Dietary fiber is known to have protective effects against obesity, type 2 diabetes, cardiovascular disease and the metabolic syndrome. Considering the emerging prevalence of these cardiometabolic disease states across the epidemiologic transition, the objective of this study is to explore these associations of dietary fiber with cardiometabolic risk factors in four countries across the epidemiologic transition...
May 16, 2018: Nutrients
https://www.readbyqxmd.com/read/29772560/impact-of-sugar-on-the-body-brain-and-behavior
#7
Clara R Freeman, Amna Zehra, Veronica Ramirez, Corinde E Wiers, Nora D Volkow, Gene-Jack Wang
Sugar is highly palatable and rewarding, both in its taste and nutritive input. Excessive sugar consumption, however, may trigger neuroadaptations in the reward system that decouple eating behavior from caloric needs and leads to compulsive overeating. Excessive sugar intake is in turn associated with adverse health conditions, including obesity, metabolic syndrome, and inflammatory diseases. This review aims to use recent evidence to connect sugar's impact on the body, brain, and behavior to elucidate how and why sugar consumption has been implicated in addictive behaviors and poor health outcomes...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772531/effects-of-oxidized-lipids-and-lipoproteins-on-cardiac-function
#8
Tahar Hajri
Oxidative modifications of lipids and lipoproteins have long been linked to the pathogenesis of cardiovascular diseases including atherosclerosis and coronary disease. Furthermore, overwhelming evidence indicate that oxidized lipids are also associated with myocardial dysfunction and cardiomyopathy. Oxidized lipid derivatives are generated by enzymatic and non-enzymatic reactions with unsaturated lipids in the cell and foods. In addition, blood LDL particles are prone to oxidation leading to the formation of oxidized LDL (oxLDL), which is often associated with obesity, diabetes and metabolic disease...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772029/prolyl-carboxypeptidase-activity-in-the-circulation-and-its-correlation-with-body-weight-and-adipose-tissue-in-lean-and-obese-subjects
#9
Kaat Kehoe, Heidi Noels, Wendy Theelen, Emilie De Hert, Shenguan Xu, An Verrijken, Thierry Arnould, Erik Fransen, Nina Hermans, Anne-Marie Lambeir, Per Venge, Luc Van Gaal, Ingrid De Meester
BACKGROUND: Prolyl carboxypeptidase (PRCP) is involved in the regulation of body weight, likely by hydrolysing alpha-melanocyte-stimulating hormone and apelin in the hypothalamus and in the periphery. A link between PRCP protein concentrations in plasma and metabolic disorders has been reported. In this study, we investigated the distribution of circulating PRCP activity and assessed its relation with body weight and adipose tissue in obese patients and patients who significantly lost weight...
2018: PloS One
https://www.readbyqxmd.com/read/29770358/association-of-central-obesity-with-sex-hormonebinding-globulin-a-cross-sectional-study-of-1166-chinese-men
#10
Fangwei Liu, Xubo Shen, Ruifeng Wang, Na Yu, Yongjun Shi, Shimin Xiong, Chengliang Xiong, Yuanzhong Zhou
Background Both sex hormone-binding globulin and central obesity have been found to be associated with metabolic and cardiovascular diseases. However, the direct relation between sex hormone-binding globulin and central obesity has not been demonstrated. Methodology We performed a cross-sectional study of 1166 male participants from Zunyi, Guizhou, western China, in 2013. Each participant completed a questionnaire and had a brief clinical exam with a fasting blood sample taken. All blood samples underwent standard laboratory testing for sex hormone-binding globulin...
2018: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/29770231/cardiovascular-outcomes-of-pcsk9-inhibitors-with-special-emphasis-on-its-effect-beyond-ldl-cholesterol-lowering
#11
REVIEW
Dhrubajyoti Bandyopadhyay, Kumar Ashish, Adrija Hajra, Arshna Qureshi, Raktim K Ghosh
PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein cholesterol (LDL-C) metabolism. PCSK9 inhibitors are monoclonal antibodies that target PCSK9 protein in liver and inhibiting this protein leads to drastically lowering harmful LDL-C level in the bloodstream. Despite widespread use of the statin, not all the high-risk patients were able to achieve targeted level of LDL-C...
2018: Journal of Lipids
https://www.readbyqxmd.com/read/29770124/does-family-history-of-obesity-cardiovascular-and-metabolic-diseases-influence-onset-and-severity-of-childhood-obesity
#12
Domenico Corica, Tommaso Aversa, Mariella Valenzise, Maria Francesca Messina, Angela Alibrandi, Filippo De Luca, Malgorzata Wasniewska
Objectives: The objectives were to evaluate (1) the metabolic profile and cardiometabolic risk in overweight/obese children at first assessment, stratifying patients according to severity of overweight and age; and (2) to investigate the relationship between family history (FH) for obesity and cardiometabolic diseases and severity of childhood obesity. Methods: In this cross-sectional, retrospective, observational study, 260 children (139 female), aged between 2...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29769110/prevalence-and-determinants-of-selected-cardio-metabolic-risk-factors-among-people-living-with-hiv-aids-and-receiving-care-in-the-south-west-regional-hospitals-of-cameroon-a-cross-sectional-study
#13
Roland Cheofor Ngu, Simeon-Pierre Choukem, Christian Akem Dimala, Julius N Ngu, Gottlieb Lobe Monekosso
OBJECTIVE: Metabolic disorders and cardiovascular risk factors are not routinely assessed in the care of HIV patients in developing countries, known to have the highest disease burden. We described the prevalence and factors associated with major cardio-metabolic risk factors (obesity, diabetes and hypertension) in HIV/AIDS patients. RESULTS: The prevalence of diabetes, hypertension and obesity were 11.3% (95% CI 8.10-15.43), 24.8% (95% CI 20.1-30.0) and 14.5% (95% CI 11...
May 16, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29768198/myocardin-related-transcription-factor-a-promotes-recruitment-of-itga5-profibrotic-progenitors-during-obesity-induced-adipose-tissue-fibrosis
#14
Jean Z Lin, Nabil Rabhi, Stephen R Farmer
Adipose tissue fibrosis is associated with inflammation and insulin resistance in human obesity. In particular, visceral fat fibrosis is correlated with hyperlipidemia and ectopic fat accumulation. Myocardin-related transcription factor A (MRTFA) is an important coactivator that mediates the transcription of extracellular matrix and other fibrogenic genes. Here, we examine the role of MRTFA in the development of adipose tissue fibrosis and identify a signaling pathway that regulates the fate of vascular progenitors...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767698/mechanisms-by-which-dietary-fatty-acids-regulate-mitochondrial-structure-function-in-health-and-disease
#15
E Madison Sullivan, Edward Ross Pennington, William D Green, Melinda A Beck, David A Brown, Saame Raza Shaikh
Mitochondria are the energy-producing organelles within a cell. Furthermore, mitochondria have a role in maintaining cellular homeostasis and proper calcium concentrations, building critical components of hormones and other signaling molecules, and controlling apoptosis. Structurally, mitochondria are unique because they have 2 membranes that allow for compartmentalization. The composition and molecular organization of these membranes are crucial to the maintenance and function of mitochondria. In this review, we first present a general overview of mitochondrial membrane biochemistry and biophysics followed by the role of different dietary saturated and unsaturated fatty acids in modulating mitochondrial membrane structure-function...
May 1, 2018: Advances in Nutrition
https://www.readbyqxmd.com/read/29767564/interorgan-metabolic-crosstalk-in-human-insulin-resistance
#16
Sofiya Gancheva, Tomas Jelenik, Elisa Álvarez-Hernández, Michael Roden
Excessive energy intake and reduced energy expenditure drive the development of insulin resistance and metabolic diseases such as obesity and type 2 diabetes mellitus. Metabolic signals derived from dietary intake or secreted from adipose tissue, gut, and liver contribute to energy homeostasis. Recent metabolomic studies identified novel metabolites and enlarged our knowledge on classic metabolites. This review summarizes the evidence of their roles as mediators of interorgan crosstalk and regulators of insulin sensitivity and energy metabolism...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29766824/adipose-derived-mesenchymal-stem-cells-in-the-treatment-of-obesity-a-systematic-review-of-longitudinal-studies-on-preclinical-evidence
#17
Fatima Saleh, Leila Itani, Simona Calugi, Riccardo Dalle Grave, Marwan El Ghoch
BACKGROUND: Obesity is an increasing global health problem, but its treatment is not yet optimal, especially in the long term. For this reason, preclinical studies have been conducted relating to a new therapeutic strategy for obesity based on adipose-derived mesenchymal stem cells (AD-MSCs). The aim of our systematic review is to summarize these findings deriving from the animal model in order to establish whether there is sufficient evidence to justify going forward to clinical studies...
May 15, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29766441/metabolomic-analysis-and-biochemical-changes-in-the-urine-and-serum-of-streptozotocin-induced-normal-and-obese-diabetic-rats
#18
Ahmed Mediani, Faridah Abas, M Maulidiani, Azliana Abu Bakar Sajak, Alfi Khatib, Chin Ping Tan, Intan Safinar Ismail, Khozirah Shaari, Amin Ismail, N H Lajis
Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal- and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done by evaluating their urine metabolites using proton nuclear magnetic resonance (1 H NMR)-based metabolomics and comparing with controls at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of the serum were also investigated...
May 15, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29764908/management-of-endocrine-disease-which-metabolic-procedure-comparing-outcomes-in-sleeve-gastrectomy-and-roux-en-y-gastric-bypass
#19
Adrian T Billeter, Javier de la Garza Herrera, Katharina M Scheurlen, Felix Nickel, Franck Billmann, Beat Müller-Stich
Obesity and its associated comorbidities have become one of the largest challenges for health care in the near future. Conservative therapy for obesity and related comorbidities have a very high failure rate and poor long-term results. Similarly, the conservative and medical management of the majority of metabolic diseases such as type 2 diabetes mellitus are only able to slow down disease progression but have no causal effect on the disease process. Obesity surgery has evolved as a highly effect therapy for severe obesity achieving long-lasting weight loss...
May 15, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29764626/25-hydroxvitamin-d-concentrations-are-not-lower-in-children-with-bronchial-asthma-atopic-dermatitis-obesity-or-attention-deficient-hyperactivity-disorder-than-in-healthy-children
#20
Thomas Reinehr, Christian Langrock, Eckard Hamelmann, Thomas Lücke, Cordula Koerner-Rettberg, Martin Holtmann, Tanja Legenbauer, Stephanie Gest, Mirjam Frank, Börge Schmidt, Katharina Radkowski, Karl-Heinz Jöckel
Vitamin D (vitD) is involved in immune regulation, and its receptor has been identified in several tissues including lung, adipose tissue, brain, and skin. Based on these observations, it has been suggested that vitD has an essential role not only in bone metabolism but also in other diseases such as atopic dermatitis (AD), bronchial asthma (BA), attention-deficit/hyperactivity disorder (ADHD), and obesity because the affected tissues express vitD receptors. Furthermore, obesity, AD, and BA are regarded as inflammatory diseases...
April 2018: Nutrition Research
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