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Novel obesity therapeutic

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https://www.readbyqxmd.com/read/28342901/the-sympathetic-neuro-adipose-connection-and-the-control-of-body-weight
#1
REVIEW
Inês Mahú, Ana I Domingos
In recent decades, obesity has become a global public health crisis irrespective of age or gender [21]. But according to historic records, concerns over appropriate maintenance of body size have been long established. For more than to 2 millennia, the main therapeutic approach to curb excess weight has been to recommend dietary restrictions and regular exercise (Haslam, 2016). Nevertheless, more contemporary studies indicate that the employment of such approaches in the treatment of severely obese patients causes metabolic adaptions which impair their long-term success in weight management [8]...
March 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28336486/mitochondrial-dysfunction-in-airway-disease
#2
Y S Prakash, Christina M Pabelick, Gary C Sieck
There is increasing appreciation that mitochondria serve cellular functions beyond oxygen sensing and energy production. Accordingly, it has become important to explore non-canonical roles of mitochondria in normal and pathophysiological processes that influence airway structure and function in the context of diseases such as asthma and COPD. Mitochondria can sense upstream processes such as inflammation, infection, tobacco smoke and environmental insults important in these diseases, and in turn can respond to such stimuli via altered mitochondrial protein expression, structure, and resultant dysfunction...
March 21, 2017: Chest
https://www.readbyqxmd.com/read/28333713/micrornas-and-lipid-metabolism
#3
Binod Aryal, Abhishek K Singh, Noemi Rotllan, Nathan Price, Carlos Fernández-Hernando
PURPOSE OF REVIEW: Work over the past decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity, and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) metabolism. RECENT FINDINGS: A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33...
March 22, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28330687/adipocyte-tumor-cell-metabolic-crosstalk-in-breast-cancer
#4
REVIEW
Andrew J Hoy, Seher Balaban, Darren N Saunders
The tumor stroma is a heterogeneous ecosystem comprising matrix, fibroblasts, and immune cells and has an important role in cancer progression. Adipocytes constitute a major component of breast stroma, and significant emerging evidence demonstrates a reciprocal metabolic adaptation between stromal adipocytes and breast cancer (BC) cells. Recent observations promote a model where adipocytes respond to cancer cell-derived endocrine and paracrine signaling to provide metabolic substrates, which in turn drive enhanced cancer cell proliferation, invasion, and treatment resistance...
March 19, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28325853/deletion-of-macrophage-mineralocorticoid-receptor-protects-hepatic-steatosis-and-insulin-resistance-through-er%C3%AE-hgf-met-pathway
#5
Yu-Yao Zhang, Chao Li, Gao-Feng Yao, Lin-Juan Du, Yuan Liu, Xiao-Jun Zheng, Shuai Yan, Jian-Yong Sun, Yan Liu, Ming-Zhu Liu, Xiaoran Zhang, Gang Wei, Wenxin Tong, Xiaobei Chen, Yong Wu, Shuyang Sun, Suling Liu, Qiurong Ding, Ying Yu, Huiyong Yin, Sheng-Zhong Duan
Although the importance of macrophages in nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) has been recognized, it remains elusive how macrophages impact hepatocytes. Mineralocorticoid receptor (MR) has been implied to play important roles in NAFLD and T2DM. However, cellular and molecular mechanisms are largely unknown. Here we report that myeloid MR knockout (MRKO) improves glucose intolerance, insulin resistance, and hepatic steatosis in obese mice. Estrogen signaling is sufficient and necessary for such improvements...
March 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28323912/sex-hormones-and-cardiometabolic-health-role-of-estrogen-and-estrogen-receptors
#6
Deborah Clegg, Andrea L Hevener, Kerrie L Moreau, Eugenia Morselli, Alfredo Criollo, Rachael E Van Pelt, Victoria J Vieira-Potter
With increased life expectancy, women will spend over three decades of life post-menopause. The menopausal transition increases susceptibility to metabolic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Thus, it is more important than ever to develop effective hormonal treatment strategies to protect aging women. Understanding the role of estrogens, and their biological actions mediated by estrogen receptors (ERs), in the regulation of cardiometabolic health is of paramount importance to discover novel targeted therapeutics...
February 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28318332/abnormality-of-adipokines-and-endothelial-dysfunction-in-mexican-obese-adolescents-with-insulin-resistance
#7
Maria Del Carmen Ortiz Segura, Blanca Estela Del Río Navarro, Benjamín Antonio Rodríguez Espino, Laurence A Marchat, Fausto Sánchez Muñoz, Santiago Villafaña, Enrique Hong, Fabián Meza-Cuenca, Patrick Mailloux Salinas, Francisco Bolaños-Jiménez, Elena Zambrano, Abel Armando Arredondo-López, Guadalupe Bravo, Fengyang Huang
PURPOSE: The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). MATERIALS AND METHODS: Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65)...
March 20, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28302047/neuroinflammation-as-a-common-mechanism-associated-with-the-modifiable-risk-factors-for-alzheimer-s-and-parkinson-s-diseases
#8
Jordan Alexander McKenzie, Lindsay J Spielman, Caitlin B Pointer, Jessica R Lowry, Ekta Bajwa, Carolyn W Lee, Andis Klegeris
Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most common causes of dementia, which increasingly contribute to morbidity and mortality worldwide. A common hallmark in the pathogenesis of these two diseases is neuroinflammation, which is initially triggered by the presence of pathological structures associated with these disorders. Chronic neuroinflammation is sustained by persistent and aberrant microglial activation in the brain, which results in damage and death of neighboring cells, including neurons and glial cells...
March 15, 2017: Current Aging Science
https://www.readbyqxmd.com/read/28295415/adipose-tissue-nad-biology-in-obesity-and-insulin-resistance-from-mechanism-to-therapy
#9
REVIEW
Shintaro Yamaguchi, Jun Yoshino
Nicotinamide adenine dinucleotide (NAD(+) ) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD(+) biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD(+) biosynthesis, together with its key downstream mediator, namely the NAD(+) -dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner...
March 15, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28294132/5-ht2c-agonists-modulate-schizophrenia-like-behaviors-in-mice
#10
Vladimir M Pogorelov, Ramona M Rodriguiz, Jianjun Cheng, Mei Huang, Claire M Schmerberg, Herbert Y Meltzer, Bryan L Roth, Alan P Kozikowski, William C Wetsel
All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side-effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests additional drug-targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT2C receptors may be a promising target for schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss promoting capabilities...
March 15, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28282929/bioactive-peptide-of-marine-origin-for-the-prevention-and-treatment-of-non-communicable-diseases
#11
REVIEW
Ratih Pangestuti, Se-Kwon Kim
Non-communicable diseases (NCD) are the leading cause of death and disability worldwide. The four main leading causes of NCD are cardiovascular diseases, cancers, respiratory diseases and diabetes. Recognizing the devastating impact of NCD, novel prevention and treatment strategies are extensively sought. Marine organisms are considered as an important source of bioactive peptides that can exert biological functions to prevent and treatment of NCD. Recent pharmacological investigations reported cardio protective, anticancer, antioxidative, anti-diabetic, and anti-obesity effects of marine-derived bioactive peptides...
March 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28282095/dietary-fat-proportionately-enhances-oxidative-stress-and-glucose-intolerance-followed-by-impaired-expression-of-the-genes-associated-with-mitochondrial-biogenesis
#12
Nabanita Das, Ashok Mandala, Sudarshan Bhattacharjee, Debasri Mukherjee, Debasish Bandyopadhyay, Sib Sankar Roy
Consumption of food that surpasses the metabolic necessity of the body leads to an epidemic condition termed obesity, which causes several metabolic disorders including oxidative damage. Dietary intervention can enlighten the mechanisms and therapeutics associated with these metabolic disorders. The reported studies related to diet include fat of different kinds and from different sources, however they lack dose response aspects. Our study highlighted the importance of dietary fat modification in modulating oxidative stress-induced glucose intolerance...
March 10, 2017: Food & Function
https://www.readbyqxmd.com/read/28273871/the-association-between-dietary-quality-and-dietary-guideline-adherence-with-mental-health-outcomes-in-adults-a-cross-sectional-analysis
#13
Amy P Meegan, Ivan J Perry, Catherine M Phillips
The prevalence of adverse mental health outcomes in adults is increasing. Although beneficial effects of selected micronutrients and foods on mental health have been reported, they do not reflect the impact of the habitual diet on mental health. Therefore, our objective is to examine potential associations between dietary quality, dietary composition and compliance with food pyramid recommendations with depressive symptoms, anxiety and well-being (assessed using CES-D, HADS-A and WHO-5 screening tools) in a cross-sectional sample of 2047 middle-aged adults...
March 5, 2017: Nutrients
https://www.readbyqxmd.com/read/28266782/systemic-immune-mechanisms-in-atopic-dermatitis-and-psoriasis-with-implications-for-treatment
#14
REVIEW
Emma Guttman-Yassky, James G Krueger, Mark G Lebwohl
Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases that negatively affect patients' quality of life. Although distinctions exist between these diseases, both are characterised by erythematous, thickened epidermal lesions that vary in intensity and affected body surface area. Early models of etiology attributed symptoms of both diseases to cutaneous inflammation at lesion sites, but recent studies have established that activated immune mediators in the circulation drive disease severity. Activation of T helper 2 (Th2) and Th22 cells in the circulation appears to be the principal initiator of acute AD pathology, with the emergence of Th1 and Th17/interleukin (IL)-23 pathway activation marking the transition to a chronic state...
March 7, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28265178/adam19-a-novel-target-for-metabolic-syndrome-in-humans-and-mice
#15
Lakshini Weerasekera, Caroline Rudnicka, Qing-Xiang Sang, Joanne E Curran, Matthew P Johnson, Eric K Moses, Harald H H Göring, John Blangero, Jana Hricova, Markus Schlaich, Vance B Matthews
Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with insulin resistance, which may ultimately culminate in type 2 diabetes (T2D). We sought to ascertain whether the human metalloproteinase A Disintegrin and Metalloproteinase 19 (ADAM19) correlates with parameters of the metabolic syndrome in humans and mice. To determine the potential novel role of ADAM19 in the metabolic syndrome, we first conducted microarray studies on peripheral blood mononuclear cells from a well-characterised human cohort...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28257569/hyperleptinemia-exacerbates-high-fat-diet-mediated-atrial-fibrosis-and-fibrillation
#16
Akira Fukui, Yuki Ikebe-Ebata, Hidekazu Kondo, Shotaro Saito, Kohei Aoki, Naoya Fukunaga, Tetsuji Shinohara, Takayuki Masaki, Yasushi Teshima, Naohiko Takahashi
BACKGROUND: Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). Although hyperleptinemia is usually a characteristic of obese subjects, the relationship with atrial fibrosis and AF is unknown. We tested the hypothesis that high-fat diet (HFD)-induced hyperleptinemia exacerbates atrial fibrosis and AF. METHODS AND RESULTS: Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob (Ob) mice were treated with a normal-fat diet (NFD) or 60% HFD...
March 3, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28257332/parathyroid-hormone-stimulates-adipose-tissue-browning-a-pathway-to-muscle-wasting
#17
Sandhya S Thomas, William E Mitch
PURPOSE OF REVIEW: Studying organ-to-organ communications (i.e. crosstalk) uncovers mechanisms regulating metabolism in several tissues. What is missing is identification of mediators of different catabolic conditions contributing to losses of adipose and muscle tissues. Identifying mediators involved in organ-to-organ crosstalk could lead to innovative therapeutic strategies because several disorders such as chronic kidney disease (CKD), cancer cachexia, and other catabolic conditions share signals of worsening metabolism and increased risk of mortality...
March 2, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28256636/elevated-fibroblast-growth-factor-21-fgf21-in-obese-insulin-resistant-states-is-normalised-by-the-synthetic-retinoid-fenretinide-in-mice
#18
Nicola Morrice, George D Mcilroy, Seshu R Tammireddy, Jennifer Reekie, Kirsty D Shearer, Mary K Doherty, Mirela Delibegović, Phillip D Whitfield, Nimesh Mody
Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinide inhibits obesity and improves glucose homeostasis in mice and has pleotropic effects on cellular pathways. To identify Fenretinide target genes, we performed unbiased RNA-seq analysis in liver from mice fed high-fat diet ± Fenretinide. Strikingly, Fgf21 was the most downregulated hepatic gene...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28244053/using-thermogenic-beige-cells-to-identify-biologically-active-small-molecules-and-peptides
#19
Ling Wu, Bin Xu
Incorporating molecular libraries in chemical biology screenings in cultured cells has been successfully used for gene discovery in many cellular processes. It has the unique potential to uncover novel mechanisms of complex cellular biology through the screening of small molecules and protein biologics in relevant cell-based assays. Recent development in the understanding and generation of thermogenic adipocytes provides opportunities for potential anti-obesity therapeutics discovery. In this chapter, we describe screening methods using thermogenic beige cells to identify novel compounds and peptides that activate adipocyte thermogenesis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28242305/intramuscular-injection-of-exogenous-leptin-induces-adiposity-glucose-intolerance-and-fatty-liver-by-repressing-the-jak2-stat3-pi3k-pathway-in-a-rat-model
#20
Lihong Wu, Guoxiong Chen, Wen Liu, Xuechao Yang, Jie Gao, Liwen Huang, Hongbing Guan, Zhengmao Li, Zhichao Zheng, Meiling Li, Weiwang Gu, Linhu Ge
Obesity, diabetes and fatty liver disease are extremely common in leptin-resistant patients. Dysfunction of leptin or its receptor is associated with obesity. The present study aimed to assess the effects of intramuscular injection of exogenous leptin or its receptor on fat deposition and leptin-insulin feedback regulation. Forty-five 40-day old female Sprague Dawley (SD) rats were injected thrice with leptin or its receptor intramuscularly. Adiposity and fat deposition were assessed by assessing the Lee's index, body weight, food intake, and total cholesterol, high density lipoprotein, low density lipoprotein, and triglyceride levels, as well as histological properties (liver and adipose tissue)...
February 24, 2017: General and Comparative Endocrinology
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