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https://www.readbyqxmd.com/read/29782892/a-glp-1-cck-fusion-peptide-harnesses-the-synergistic-effects-on-metabolism-of-cck-1-and-glp-1-receptor-agonism-in-mice
#1
David C Hornigold, Emma Roth, Victor Howard, Sarah Will, Stephanie Oldham, Matthew P Coghlan, Clemence Blouet, James L Trevaskis
Combination approaches for the treatment of metabolic diseases such as obesity and diabetes are becoming increasingly relevant. Co-administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist with a cholecystokinin receptor-1 (CCKR1) agonist exert synergistic effects on weight loss in obese rodents. Here, we report on the effects of a novel fusion peptide (C2816) comprised of a stabilized GLP-1R agonist, AC3174, and a CCKR1-selective agonist, AC170222. C2816 was constructed such that AC3174 was linked to the N-terminus of AC170222, thus preserving the C-terminal amide of the CCK moiety...
May 18, 2018: Appetite
https://www.readbyqxmd.com/read/29781744/endurance-training-alters-ykl40-perm1-and-hsp70-skeletal-muscle-protein-contents-in-men-with-type-2-diabetes-mellitus
#2
Christian Brinkmann, Anika Kuckertz, Thorsten Schiffer, Wilhelm Bloch, Hans-Georg Predel, Klara Brixius
BACKGROUND: The fight against type 2 diabetes mellitus (T2DM) is tremendously challenging. This pilot study investigates whether endurance training (3 times per week for 3 months, moderate intensity) can change the skeletal muscle protein contents of chitinase-3-like protein-1 (YKL40), peroxisome proliferator-activated receptor y coactivator-1 and estrogen-related receptor-induced regulator in muscle-1 (PERM1) and heat-shock protein-70 (HSP70), which have been discussed as novel therapeutically relevant targets...
May 21, 2018: Endocrine Research
https://www.readbyqxmd.com/read/29777802/derivation-and-characterization-of-a-ucp1-reporter-human-es-cell-line
#3
Suranjit Mukherjee, Tuo Zhang, Lauretta A Lacko, Lei Tan, Jenny Zhaoying Xiang, Jason M Butler, Shuibing Chen
Interest in human brown fat as a novel therapeutic target to tackle the growing obesity and diabetes epidemic has increased dramatically in recent years. While much insight into brown fat biology has been gained from murine cell lines and models, few resources are available to study human brown fat in vitro, which makes the need for new ways to derive and study human brown adipocytes imperative. Human ES cell based reporter systems present an excellent tool to identify, mark, and purify cell populations of choice...
April 22, 2018: Stem Cell Research
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
#4
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/29769703/preoperative-thyroid-function-and-weight-loss-after-bariatric-surgery
#5
João Sérgio Neves, Pedro Souteiro, Sofia Castro Oliveira, Jorge Pedro, Daniela Magalhães, Vanessa Guerreiro, Maria Manuel Costa, Rita Bettencourt-Silva, Ana Cristina Santos, Joana Queirós, Ana Varela, Paula Freitas, Davide Carvalho
Thyroid function has an important role on body weight regulation. However, the impact of thyroid function on weight loss after bariatric surgery is still largely unknown. We evaluated the association between preoperative thyroid function and the excess weight loss 1 year after surgery, in 641 patients with morbid obesity who underwent bariatric surgery. Patients with a history of thyroid disease, treatment with thyroid hormone or antithyroid drugs and those with preoperative evaluation consistent with overt hypothyroidism or hyperthyroidism were excluded...
May 16, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29760587/the-role-of-adipokines-in-skeletal-muscle-inflammation-and-insulin-sensitivity
#6
REVIEW
Thomas Nicholson, Chris Church, David J Baker, Simon W Jones
Background: There is currently an unmet clinical need to develop better pharmacological treatments to improve glucose handling in Type II Diabetes patients with obesity. To this end, determining the effect of obesity-associated adipokines on skeletal muscle insulin sensitivity has emerged as an important area of drug discovery research. This review draws together the data on the functional role of adipokines on skeletal muscle insulin signalling, highlights several understudied novel adipokines and provides a perspective on the direction of future research...
2018: Journal of Inflammation
https://www.readbyqxmd.com/read/29758288/micrornas-in-brown-and-beige-fat
#7
REVIEW
Deborah Goody, Alexander Pfeifer
Brown adipose tissue (BAT) dissipates energy as heat and its activity correlates with leanness in human adults. Understanding the mechanisms behind the activation of BAT and the process of "browning", i.e. the appearance of inducible brown adipocytes called beige or brite (brown-in-white) cells in white adipose tissue (WAT), is of great interest for developing novel therapies to combat obesity. MicroRNAs (miRNAs) are small transcriptional regulators that control gene expression in a variety of tissues, including WAT and BAT...
May 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29755288/roles-of-perilipins-in-diseases-and-cancers
#8
Pengpeng Zhang, Lian Meng, Lingxie Song, Juan Du, Shutong Du, Wenwen Cui, Chunxia Liu, Feng Li
Perilipins, an ancient family of lipid droplet-associated proteins, are embedded in a phospho-lipid monolayer of intracellular lipid droplets. The core of lipid droplets is composed of neutral fat, which mainly includes triglyceride and cholesterol ester. Perilipins are closely related to the function of lipid droplets, and they mediate lipid metabolism and storage. Therefore, perilipins play an important role in the development of obesity, diabetes, cancer, hepatic diseases, atherosclerosis, and carcinoma, which are caused by abnormal lipid metabolism...
May 2018: Current Genomics
https://www.readbyqxmd.com/read/29753771/mir-199a-3p-regulates-brown-adipocyte-differentiation-through-mtor-signaling-pathway
#9
Yao Gao, Yan Cao, Xianwei Cui, Xingyun Wang, Yahui Zhou, Fangyan Huang, Xing Wang, Juan Wen, Kaipeng Xie, Pengfei Xu, Xirong Guo, Lianghui You, Chenbo Ji
Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans...
May 10, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29733374/fatty-acids-and-their-amide-derivatives-from-endophytes-new-therapeutic-possibilities-from-a-hidden-source
#10
Rabia Tanvir, Aqeel Javeed, Yasir Rehman
Fatty acid and their amide derivatives are natural self-defense agents in plants. They have been observed to be broadly bioactive against a variety of disease agents. The mechanism of action understood so far being their targeting the protein synthesis and causing leakage of the intracellular components. Owing to their broad bioactivity, the fatty acids and their amides as therapeutics can cover a wide range of indications such as cancer, bacterial infections, parasitic infection, inflammations, diabetes and obesity to name a few...
May 3, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29729191/caspase-recruitment-domain-protein-6-protects-against-hepatic-steatosis-and-insulin-resistance-by-suppressing-ask1
#11
Peng Sun, Qiang Zeng, Daqing Cheng, Kuo Zhang, Jilin Zheng, Yupeng Liu, Yu-Feng Yuan, Yi-Da Tang
The rapidly increasing prevalence of metabolic disorders associated with non-alcoholic fatty liver disease (NAFLD) warrants further study of the underlying mechanism to identify key regulators as targets for the development of therapeutic interventions. Caspase recruitment domain protein 6 (Card6), as a member of the CARD family that regulates cell death and immunity, may potentially control this process. Indeed, Card6 downregulation was found to be closely associated with the fatty livers observed in NAFLD patients, obese mice and a palmitate-treated hepatocyte model...
May 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29729104/the-impact-of-diet-induced-hepatic-steatosis-in-a-murine-model-of-hepatic-ischemia-reperfusion-injury
#12
Kim H H Liss, Kyle S McCommis, Kari T Chambers, Terri A Pietka, George G Schweitzer, Sara L Park, ILKe Nalbantoglu, Carla J Weinheimer, Angela M Hall, Brian N Finck
The prevalence of obesity-associated nonalcoholic fatty liver disease has significantly increased over the past decade and end stage liver disease secondary to nonalcoholic steatohepatitis has become one of the most common indications for liver transplantation. This both increases the demand for organs and decreases the availability of donor livers deemed suitable for transplantation. While in the past many steatotic livers were discarded due to concerns over enhanced susceptibility to ischemia reperfusion injury and organ failure, the discrepancy between supply and demand has resulted in increasing use of expanded criteria donor organs including steatotic livers...
May 5, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29722568/liver-fat-imaging-a-clinical-overview-of-ultrasound-ct-and-mr-imaging
#13
Yingzhen Zhang, Kathryn J Fowler, Gavin Hamilton, Jennifer Cui, Ethan Z Sy, Michelle Balanay, Jonathan C Hooker, Nikolaus M Szeverenyi, Claude B Sirlin
Hepatic steatosis is a frequently encountered imaging finding that may indicate chronic liver disease, the most common of which is nonalcoholic fatty liver disease (NAFLD). NAFLD is implicated in the development of systemic diseases and its progressive phenotype, nonalcoholic steatohepatitis (NASH), leads to increased liver-specific morbidity and mortality. With the rising obesity epidemic and advent of novel therapeutics aimed at altering metabolism, there is a growing need to quantify and monitor liver steatosis...
May 3, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29720225/the-role-of-exercise-combined-with-tocilizumab-in-visceral-and-epicardial-adipose-tissue-and-gastric-emptying-rate-in-abdominally-obese-participants-protocol-for-a-randomised-controlled-trial
#14
Regitse Højgaard Christensen, Anne-Sophie Wedell-Neergaard, Louise Lang Lehrskov, Grit Elster Legård, Emma Berndt Dorph, Stine Nymand, Maria Korf Ball, Morten Zacho, Robin Christensen, Helga Ellingsgaard, Jaya Birgitte Rosenmeier, Rikke Krogh-Madsen, Bente Klarlund Pedersen, Kristian Karstoft
BACKGROUND: Exercise reduces the amount of visceral adipose tissue (VAT) and the risk of cardiometabolic diseases. The underlying mechanisms responsible for these exercise-induced adaptations are unclear, but they may involve lipolytic actions of interleukin-6 (IL-6). Contracting skeletal muscles secrete IL-6, leading to increased circulating IL-6 levels in response to exercise. The aim of this study is to investigate whether IL-6 is involved in mediating the effects of exercise on visceral and epicardial adipose tissue volume and glycaemic control...
May 2, 2018: Trials
https://www.readbyqxmd.com/read/29717059/fed-exosome-extracellular-vesicles-and-cell-cell-communication-in-metabolic-regulation
#15
REVIEW
Isabella Samuelson, Antonio J Vidal-Puig
Extracellular vesicles (EVs) have emerged as a novel messaging system of the organism, mediating cell-cell and interorgan communication. Through their content of proteins and nucleic acids, as well as membrane proteins and lipid species, EVs can interact with and modulate the function of their target cells. The regulation of whole-body metabolism requires cross-talk between key metabolic tissues including adipose tissue (AT), the liver and skeletal muscle. Furthermore, the regulation of nutrient/energy allocation during pregnancy requires co-ordinated communication between the foetus and metabolic organs of the mother...
May 1, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/29717038/lipidomic-profiling-reveals-soluble-epoxide-hydrolase-as-a-therapeutic-target-of-obesity-induced-colonic-inflammation
#16
Weicang Wang, Jun Yang, Jianan Zhang, Yuxin Wang, Sung Hee Hwang, Weipeng Qi, Debin Wan, Daeyoung Kim, Jia Sun, Katherine Z Sanidad, Haixia Yang, Yeonhwa Park, Jun-Yan Liu, Xinfeng Zhao, Xiaohui Zheng, Zhenhua Liu, Bruce D Hammock, Guodong Zhang
Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue...
May 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29716941/increased-rtn3-leads-to-obesity-and-hypertriglyceridemia-by-interacting-with-hspa5
#17
Rong Xiang, Liang-Liang Fan, Hao Huang, Ya-Qin Chen, Wanxia He, Shuai Guo, Jing-Jing Li, Jie-Yuan Jin, Ran Du, Riqiang Yan, Kun Xia
Background -Reticulon 3 (RTN3) is an endoplasmic reticulum protein that has been previously shown to play a role in neurodegenerative diseases, but little is known about its role in lipid metabolism. Methods -Obesity patients (149), hypertriglyceridemia patients (343), and healthy controls (84) were enrolled to assess their levels of RTN3. To explore pathophysiological roles of RTN3 in the control of lipid metabolism, we utilized Tg-RTN3 and RTN3-null transgenic mouse models and multiple C. elegans strains for molecular characterization...
May 1, 2018: Circulation
https://www.readbyqxmd.com/read/29705606/neuroprotective-effects-of-protein-tyrosine-phosphatase-1b-inhibitor-on-cerebral-ischemia-reperfusion-in-mice
#18
Meiling Sun, Hisanao Izumi, Yasuharu Shinoda, Kohji Fukunaga
Akt (Protein kinase B, PKB), a serine/threonine kinase, plays a critical role in cell development, growth, and survival. Akt phosphorylation mediates a neuroprotective effect against ischemic injury. Recently, a protein-tyrosine phosphatase-1B (PTP1B) inhibitor (KY-226) was developed to elicit anti-diabetic and anti-obesity effects via enhancement of insulin signaling. Previously, we reported that the nonselective PTP1B inhibitor, sodium orthovanadate, rescued neurons from delayed neuronal death during brain ischemia...
April 26, 2018: Brain Research
https://www.readbyqxmd.com/read/29698569/preemptive-activation-of-the-integrated-stress-response-protects-mice-from-diet-induced-obesity-and-insulin-resistance-via-fibroblast-growth-factor-21-induction
#19
Xu Xu, Christopher Krumm, Jae-Seon So, Curtis J Bare, Corey Holman, Jesper Gromada, David E Cohen, Ann-Hwee Lee
The integrated stress response (ISR) is a signaling system in which the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) by stress-specific kinases and the subsequent activation of activation transcription factor (ATF) 4 help restore cellular homeostasis following exposure to environmental stresses. ISR activation has been observed in metabolic diseases including hepatic steatosis, steatohepatitis and insulin resistance, but it remains unclear whether ISR contributes to the disease pathogenesis, or represents an innate defense mechanism against metabolic stresses...
April 26, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29691953/circulating-mots-c-levels-are-decreased-in-obese-male-children-and-adolescents-and-associated-with-insulin-resistance
#20
Caiqi Du, Cai Zhang, Wei Wu, Yan Liang, Anru Wang, Shimin Wu, Yue Zhao, Ling Hou, Qin Ning, Xiaoping Luo
BACKGROUND AND AIMS: A novel bioactive peptide, mitochondrial-derived peptide (MOTS-c), has recently attracted attention as a potential prevention or therapeutic option for obesity and type 2 diabetes mellitus (T2DM). MOTS-c profiles have not yet been reported in human obesity and T2DM. We aimed to determine circulating MOTS-c levels in obesity and explore the association between MOTS-c levels and various metabolic parameters. METHODS: In this case-control study, 40 obese children and adolescents (27 males) and 57 controls (40 males) were recruited in the Hubei Province of China in 2017...
April 25, 2018: Pediatric Diabetes
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