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Novel obesity therapeutic

Ryan D Sheldon, Kayla M Kanosky, Kevin D Wells, Lili Miles, James W Perfield, Stavra Xanthakos, Thomas H Inge, R Scott Rector
BACKGROUND: Mechanisms responsible for progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain poorly defined. METHODS: To examine the potential contribution of adipose tissue to NAFLD progression, we performed a complete transcriptomic analysis using RNA-sequencing (RNA-seq) on intra-abdominal adipose tissue (IAT) from severely obese adolescents (Mage 16.9±0.4 yrs; BMI z-score 2.7±0.1) undergoing bariatric surgery and liver biopsy categorized into 3 groups; No steatosis (Normal, n=8), steatosis only (n=13), or NASH (n=10) by liver histology...
October 7, 2016: Physiological Genomics
Mohan Raizada
Hypertension (HTN) is the most prevalent modifiable risk for cardiovascular disease (CVD) and disorders directly influencing CVD (i.e. obesity, diabetes, chronic kidney disease, obstructive sleep apnea, etc.). About one billion people worldwide have HTN, with American adults having 90% lifetime risk of developing HTN. Despite aggressive campaign for lifestyle changes and advances in drug therapy, HTN remains an immense health, emotional, and economic challenge. This is due, in part, to the fact that ∼50% of HTN patients' blood pressure remains uncontrolled and ∼20% of HTN patients are resistant to or require > antihypertensive drugs...
September 2016: Journal of Hypertension
Amal Akour, Violet Kasabri, Nailya Boulatova, Yasser Bustanji, Randa Naffa, Dana Hyasat, Nahla Khawaja, Haidar Bustanji, Ayman Zayed, Munther Momani
AIMS: Type 2 diabetes mellitus (T2DM) and prediabetes (pre-DM) are associated with changes in levels of metabolic markers. The main aim of this study is to compare the levels of omentin, irisin, endothelin-1, nesfatin, hepatocyte growth factor (HGF), fibroblast growth factor, and oxytocin (OXT) between normoglycemic and pre-DM/T2DM obese Jordanian patients. METHODS: One hundred and ninety-eight adult Jordanian subjects were recruited. Demographic data and clinical parameters were collected...
October 18, 2016: Acta Diabetologica
Hao-Wei Teng, Man-Hsin Hung, Li-Ju Chen, Mao-Ju Chang, Feng-Shu Hsieh, Ming-Hsien Tsai, Jui-Wen Huang, Chih-Lung Lin, Hsiang-Wen Tseng, Zong-Keng Kuo, Jeng-Kai Jiang, Shung-Haur Yang, Chung-Wai Shiau, Kuen-Feng Chen
Protein tyrosine phosphatase 1B (PTP1B) is known to promote the pathogenesis of diabetes and obesity by negatively regulating insulin and leptin pathways, but its role associated with colon carcinogenesis is still under debate. In this study, we demonstrated the oncogenic role of PTP1B in promoting colon carcinogenesis and predicting worse clinical outcomes in CRC patients. By co-immunoprecipitation, we showed that PITX1 was a novel substrate of PTP1B. Through direct dephosphorylation at Y160, Y175 and Y179, PTP1B destabilized PITX1, which resulted in downregulation of the PITX1/p120RasGAP axis...
October 18, 2016: Scientific Reports
Chengyuan Tang, Juan Cai, Zheng Dong
Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, but the underlying mechanism is poorly understood. Szeto et al. now unravel a central role of mitochondrial dysfunction in a high fat diet-induced glomerulopathy and proximal tubular injury. Moreover, they demonstrate the renoprotective effect of SS31, a mitochondria-targeted antioxidant, in related models. Targeting mitochondria may offer a novel strategy for the therapy of obesity-related kidney disease...
November 2016: Kidney International
E M Ribe, S Lovestone
As populations across the world both age and become more obese, the numbers of individuals with Alzheimer's disease and diabetes are increasing; posing enormous challenges for society and consequently becoming priorities for governments and global organizations. These issues, an ageing population at risk of neurodegenerative diseases such as Alzheimer's disease and an increasingly obese population at risk of metabolic alterations such as type 2 diabetes, are usually considered as independent conditions, but increasing evidence from both epidemiological and molecular studies link these disorders...
October 14, 2016: Journal of Internal Medicine
Ricardo Zorron, Alcides Branco, Jose Sampaio, Claudia Bothe, Tido Junghans, Gyurdzhan Rasim, Johann Pratschke, Safak Guel-Klein
BACKGROUND: The anatomical and physiological changes after Roux-en-Y gastric bypass for morbid obesity can lead to severe hyperinsulinemic hypoglycemia with neuroglycopenia in a small percentage of patients. The exact physiologic mechanism is not completely understood. Surgical reversal to the original anatomy and distal or total pancreatectomy are current therapeutic options to reverse the hypoglycemic effect, with substantial associated morbidity. Our group reports a pilot clinical series of a novel surgical technique using one-anastomosis jejunal interposition with gastric remnant resection (Branco-Zorron Switch)...
October 13, 2016: Obesity Surgery
Youngjoo Lee, Jiyeon Kim, Jinho An, Sungwon Lee, Heetae Lee, Hyunseok Kong, Youngcheon Song, Hye Ran Choi, Ji-Wung Kwon, Daekeun Shin, Chong-Kil Lee, Kyungjae Kim
Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology...
October 17, 2016: Biomolecules & Therapeutics
Ayman Grada, Vincent Falanga
The number of individuals with chronic cutaneous wounds has been increasing worldwide due to an aging population, diabetes, obesity, and cardiovascular disease. In the United States, almost seven million Americans have chronic skin ulcers. Many therapeutic approaches have been used. However, the treatment outcomes are not always ideal because of failure to achieve complete wound closure in around 60% of cases, scarring, and high rate of recurrence. Therefore, there is a need for more effective therapies. Stem cells offer promising possibilities...
October 6, 2016: Surgical Technology International
David A Calhoun
Resistant hypertension has for many decades been defined as difficult-to-treat hypertension in order to identify patients who may benefit from special diagnostic and/or therapeutic considerations. Recently, the term "refractory hypertension" has been proposed as a novel phenotype of antihypertensive failure, that is, patients whose blood pressure cannot be controlled with maximal treatment. Early studies of this phenotype indicate that it is uncommon, affecting less than 5% of patients with resistant hypertension...
September 2016: Korean Circulation Journal
Fortunata Carbone, Claudia La Rocca, Paola De Candia, Claudio Procaccini, Alessandra Colamatteo, Teresa Micillo, Veronica De Rosa, Giuseppe Matarese
The filed that links immunity and metabolism is rapidly expanding. The adipose tissue, by secreting a series of immune regulators called adipokines, represents the common mediator linking metabolic processes and immune system functions. The dysregulation of adipokine secretion, occurring in obese individuals or in conditions of malnutrition or dietary restriction, affects the activity of immune cells resulting in inflammatory autoimmune responses or increased susceptibility to infectious diseases. Alterations of cell metabolism that characterize several autoimmune diseases strongly support the idea that the immune tolerance is also regulated by metabolic pathways...
October 5, 2016: Seminars in Immunology
Hoang Kim Tu Trinh, Ga-Young Ban, Ji-Ho Lee, Hae-Sim Park
Elderly asthma (EA) is regarded as a distinct phenotype of asthma and is associated with age-related changes in airway structure and alterations in lung function and immune responses. EA is difficult to diagnose because of aging and co-morbidities, and overlaps with fixed airway obstructive disease. Novel modalities to differentiate between EA and chronic obstructive pulmonary disease (COPD) are necessary. A multifaceted approach, including clinical history, smoking habits, atopy, and measurement of lung function, is mandatory to differentiate asthma from COPD...
October 6, 2016: Drugs & Aging
Yong Chen, Ruping Pan, Alexander Pfeifer
Fat tissue is well known for its capacity to store energy and its detrimental role in obesity and metaflammation. However, humans possess different types of fat that have different functions in physiology and metabolic diseases. Apart from white adipose tissue (WAT), the body's main energy storage, there is also brown adipose tissue (BAT) that dissipates energy as a defense against cold and maintains energy balance for the whole body. BAT is present not only in newborns but also in adult humans and its mass correlates with leanness...
October 4, 2016: Pflügers Archiv: European Journal of Physiology
U Smith, B B Kahn
Obesity, the major cause of the current global epidemic of type 2 diabetes (T2D), induces insulin resistance in peripheral insulin target tissues. Several mechanisms have been identified related to cross-talk between adipose tissue, skeletal muscle and liver. These mechanisms involve both increased free fatty acid release and altered secretion of adipokines from adipose tissue. A major determinant of metabolic health is the ability of subcutaneous adipose tissue (SAT) to store excess fat rather than allowing it to accumulate in ectopic depots including liver (i...
October 3, 2016: Journal of Internal Medicine
Hiroko Inoue, Atsuhiro Kishimoto, Ryoko Ushikoshi-Nakayama, Ayaka Hasaka, Ayako Takahashi, Koufuchi Ryo, Takashi Muramatsu, Fumio Ide, Kenji Mishima, Ichiro Saito
Resveratrol is a natural polyphenol produced by plants in response to environmental stress. This compound has been shown to have pharmacological effects against a wide range of diseases including neurological, hepatic, cardiovascular and autoimmune conditions. The non-obese diabetic (NOD) mouse, in which loss of lacrimal and salivary gland function occurs, has been studied as an animal model for Sjögren's syndrome. In this study, we confirmed that administration of resveratrol results in increased secretion of saliva in NOD mice...
September 2016: Journal of Clinical Biochemistry and Nutrition
Florian W Kiefer
The view of adipose tissue as solely a fat storing organ has changed significantly over the past two decades with the discoveries of numerous adipocyte-secreted factors, so called adipokines, and their endocrine functions throughout the body. The newest chapter added to this story is the finding that adipose tissue is also a thermogenic organ contributing to energy expenditure through actions of specialized, heat-producing brown or beige adipocytes. In contrast to bone fide brown adipocytes, beige cells develop within white fat depots in response to various stimuli such as prolonged cold exposure, underscoring the great thermogenic plasticity of adipose tissue...
August 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
Daniel Hormaechea-Agulla, Enrique Gómez-Gómez, Alejandro Ibáñez-Costa, Julia Carrasco-Valiente, Esther Rivero-Cortés, Fernando L-López, Sergio Pedraza-Arevalo, José Valero-Rosa, Rafael Sánchez-Sánchez, Rosa Ortega-Salas, María M Moreno, Manuel D Gahete, José López-Miranda, María J Requena, Justo P Castaño, Raúl M Luque
Ghrelin-O-acyltransferase (GOAT) is the key enzyme regulating ghrelin activity, and has been proposed as a potential therapeutic target for obesity/diabetes and as a biomarker in some endocrine-related cancers. However, GOAT presence and putative role in prostate-cancer (PCa) is largely unknown. Here, we demonstrate, for the first time, that GOAT is overexpressed (mRNA/protein-level) in prostatic tissues (n = 52) and plasma/urine-samples (n = 85) of PCa-patients, compared with matched controls [healthy prostate tissues (n = 12) and plasma/urine-samples from BMI-matched controls (n = 28), respectively]...
September 28, 2016: Cancer Letters
Sarbani Ghoshal, Qingzhang Zhu, Alice Asteian, Hua Lin, Haifei Xu, Glen Ernst, James C Barrow, Baoji Xu, Michael D Cameron, Theodore M Kamenecka, Anutosh Chakraborty
OBJECTIVE: Obesity and type 2 diabetes (T2D) lead to various life-threatening diseases such as coronary heart disease, stroke, osteoarthritis, asthma, and neurodegeneration. Therefore, extensive research is ongoing to identify novel pathways that can be targeted in obesity/T2D. Deletion of the inositol pyrophosphate (5-IP7) biosynthetic enzyme, inositol hexakisphosphate kinase-1 (IP6K1), protects mice from high fat diet (HFD) induced obesity (DIO) and insulin resistance. Yet, whether this pathway is a valid pharmacologic target in obesity/T2D is not known...
October 2016: Molecular Metabolism
Soledad Pitra, Yumei Feng, Javier E Stern
BACKGROUND: Hypertension and obesity are highly interrelated diseases, being critical components of the metabolic syndrome. Despite the growing prevalence of this syndrome in the world population, efficient therapies are still missing. Thus, identification of novel targets and therapies are warranted. An enhanced activity of the hypothalamic renin-angiotensin system (RAS), including the recently discovered prorenin (PR) and its receptor (PRR), has been implicated as a common mechanism underlying aberrant sympatho-humoral activation that contributes to both metabolic and cardiovascular dysregulation in the metabolic syndrome...
October 2016: Molecular Metabolism
Maria Frantzi, Zoi Klimou, Manousos Makridakis, Jerome Zoidakis, Agnieszka Latosinska, Daniel M Borràs, Bart Janssen, Ioanna Giannopoulou, Vasiliki Lygirou, Andreas C Lazaris, Nicholas P Anagnou, Harald Mischak, Maria G Roubelakis, Antonia Vlahou
Bladder cancer (BC) is the second most common malignancy of the genitourinary system, characterized by the highest recurrence rate of all cancers. Treatment options are limited; thus a thorough understanding of the underlying molecular mechanisms is needed to guide the discovery of novel therapeutic targets. Profilins are actin binding proteins with attributed pleiotropic functions to cytoskeletal remodeling, cell adhesion, motility, even transcriptional regulation, not fully characterized yet. Earlier studies from our laboratory revealed that decreased tissue levels of Profilin-1 (PFN1) are correlated with BC progression to muscle invasive disease...
September 23, 2016: Oncotarget
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