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obesity AND GLP-1

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https://www.readbyqxmd.com/read/28919062/progress-and-challenges-in-anti-obesity-pharmacotherapy
#1
REVIEW
Daniel H Bessesen, Luc F Van Gaal
Obesity is a serious and growing worldwide health challenge. Healthy lifestyle choices are the foundation of obesity treatment. However, weight loss can lead to physiological adaptations that promote weight regain. As a result, lifestyle treatment alone typically produces only modest weight loss that is difficult to sustain. In other metabolic diseases, pharmacotherapy is an accepted adjunct to lifestyle. Several anti-obesity drugs have been approved in the USA, European Union, Australia, and Japan including sympathomimetics, pancreatic lipase inhibitors, GABAA receptor activators, a serotonin 2C receptor agonist, opioid antagonist, dopamine-norepinephrine reuptake inhibitor, and glucagon-like peptide-1 (GLP-1) receptor agonists...
September 14, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28918389/glucagon-like-peptide-1-receptor-agonists-for-the-management-of-obesity-and-non-alcoholic-fatty-liver-disease-a-novel-therapeutic-option
#2
REVIEW
Gauri Dhir, Kenneth Cusi
Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM), and is associated with a cluster of metabolic factors that lead to poor cardiovascular outcomes. In non-alcoholic fatty liver disease (NAFLD), liver fat (triglyceride) accumulation closely mirrors adipose tissue dysfunction and insulin resistance in obesity and T2DM. It is now recognized as the most common chronic liver disease in Westernized societies, often progressing to more severe forms of the disease such as nonalcoholic steatohepatitis (NASH), or cirrhosis and hepatocellular carcinoma...
September 15, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28905106/recombinant-mouse-osteocalcin-secreted-by-lactococcus-lactis-promotes-glucagon-like-peptide-1-induction-in-stc-1-cells
#3
Fu Namai, Suguru Shigemori, Koichi Sudo, Takashi Sato, Yoshinari Yamamoto, Shireen Nigar, Tasuku Ogita, Takeshi Shimosato
An osteoblastic protein, osteocalcin (OC), exists in vivo in two forms: carboxylated OC, and uncarboxylated or low-carboxylated OC (ucOC). ucOC acts as a hormone to regulate carbon and energy metabolism. Recent studies demonstrated that ucOC exerts insulinotropic effects, mainly through the glucagon-like peptide 1 (GLP-1) pathway. GLP-1 is an insulinotropic hormone secreted by enteroendocrine L cells in the small intestine. Thus, efficient delivery of ucOC to the small intestine may be a new therapeutic option for metabolic diseases such as diabetes and obesity...
September 13, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28898910/balanced-coagonist-of-glp-1-and-glucagon-receptors-corrects-dyslipidemia-by-improving-fgf21-sensitivity-in-hamster-model
#4
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Hiren M Patel, Dheerendra Pandey, Dipam Patel, Brijesh Sutariya, Maulik Patel, Rajesh Bahekar, Mukul R Jain
Hyperlipidemia is often associated with obesity and diabetes, and can lead to serious complications like atherosclerosis and fatty liver disease. Coagonist of GLP-1 and glucagon receptors is a therapy under clinical investigation for treatment of obesity and diabetes. In this study, we have characterized the mechanism of hypolipidemic effect of a balanced coagonist using high cholesterol-fed hamsters. Tyloxapol-induced hypertriglyceridemia, lipolysis in adipose tissue, and bile homeostasis were assessed after repeated dose treatment of the coagonist of GLP-1 and glucagon receptors (Aib2 C24 chimera 2, SC)...
September 12, 2017: Drug Research
https://www.readbyqxmd.com/read/28894301/lateral-hypothalamic-glp-1-receptors-are-critical-for-the-control-of-food-reinforcement-ingestive-behavior-and-body-weight
#5
L López-Ferreras, J E Richard, E E Noble, K Eerola, R H Anderberg, K Olandersson, L Taing, S E Kanoski, M R Hayes, K P Skibicka
Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28890700/dietary-capsaicin-improves-glucose-homeostasis-and-alters-the-gut-microbiota-in-obese-diabetic-ob-ob-mice
#6
Jun-Xian Song, Hui Ren, Yuan-Feng Gao, Chong-You Lee, Su-Fang Li, Feng Zhang, Long Li, Hong Chen
Background: The effects of capsaicin on obesity and glucose homeostasis are still controversial and the mechanisms underlying these effects remain largely unknown. This study aimed to investigate the potential relationship between the regulation of obesity and glucose homeostasis by dietary capsaicin and the alterations of gut microbiota in obese diabetic ob/ob mice. Methods: The ob/ob mice were subjected to a normal, low-capsaicin (0.01%), or high-capsaicin (0.02%) diet for 6 weeks, respectively. Obesity phenotypes, glucose homeostasis, the gut microbiota structure and composition, short-chain fatty acids, gastrointestinal hormones, and pro-inflammatory cytokines were measured...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28886439/chronic-high-sucrose-diet-increases-fibroblast-growth-factor-21-production-and-energy-expenditure-in-mice
#7
Ryuya Maekawa, Yusuke Seino, Hidetada Ogata, Masatoshi Murase, Atsushi Iida, Kaori Hosokawa, Erina Joo, Norio Harada, Shin Tsunekawa, Yoji Hamada, Yutaka Oiso, Nobuya Inagaki, Yoshitaka Hayashi, Hiroshi Arima
Excess carbohydrate intake causes obesity in humans. On the other hand, acute administration of fructose, glucose or sucrose in experimental animals has been shown to increase the plasma concentration of anti-obesity hormones such as glucagon-like peptide 1 (GLP-1) and Fibroblast growth factor 21 (FGF21), which contribute to reducing body weight. However, the secretion and action of GLP-1 and FGF21 in mice chronically fed a high-sucrose diet has not been investigated. To address the role of anti-obesity hormones in response to increased sucrose intake, we analyzed mice fed a high-sucrose diet, a high-starch diet or a normal diet for 15 weeks...
July 25, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28873389/treatment-of-diabetes-and-obesity-by-rationally-designed-peptide-agonists-functioning-at-multiple-metabolic-receptors
#8
Noushafarin Khajavi, Heike Biebermann, Matthias Tschöp, Richard DiMarchi
Obesity and its comorbidities such as type 2 diabetes constitute major worldwide health threats, and the identification of an effective medical intervention has emerged as a global priority. The limited effectiveness of historical, anti-obesity treatments is commonly attributed to the complexity of the disease and the redundancy of metabolic regulatory mechanisms that sustain body weight. At the forefront of obesity research is the development of combinational drug therapies that simultaneously target multiple regulatory pathways, which promote dysfunctional metabolism...
2017: Endocrine Development
https://www.readbyqxmd.com/read/28870812/thyroidectomy-stimulates-glucagon-like-peptide-1-secretion-and-attenuates-hepatic-steatosis-in-high-fat-fed-rats
#9
Jong Yeon Kang, Mikyung Kim, Yuna Kang, Wonmok Lee, Tae Kyung Ha, Ji Hae Seo, Young Gil Son, Eunyoung Ha
Thyroid hormones (THs) as a therapeutic intervention to treat obesity has been tried but the effect of THs on body weight and the mechanistic details of which are far from clear. This study was designed to determine and elucidate the mechanistic details of metabolic action of THs in high-fat diet (HFD) fed Sprague Dawley (SD) rats. Rats were made surgically hypothyroid (thyroidectomy, Thx). Body weights and food and water intake profoundly decreased in HFD fed thyroidectomized group (HN Thx). Results showed that delayed insulin response, increased total cholesterol, high-density lipoprotein, and low-density lipoprotein in HN Thx...
September 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28855269/roles-of-increased-glycemic-variability-glp-1-and-glucagon-in-hypoglycaemia-after-roux-en-y-gastric-bypass
#10
George Tharakan, Preeshila Behary, Nicolai Jacob Wewer Albrechtsen, Harvinder Chahal, Julia Kenkre, Alexander D Miras, Ahmed R Ahmed, Jens Juul Holst, Steve R Bloom, Tricia Mei Mei Tan
Objective Roux-en-Y Gastric Bypass (RYGB) surgery is currently the most effective treatment for diabetes and obesity. An increasingly recognized complication of RYGB surgery is postprandial hypoglycemia (PPH). The pathophysiology of PPH remains unclear with multiple mechanisms suggested including nesidioblastosis, altered insulin clearance and increased glucagon-like-1 peptide (GLP-1) secretion. Whilst many PPH patients respond to dietary modification, some have severely disabling symptoms. Multiple treatments have been trialled ranging from acarbose, to both GLP-1 agonists and antagonists, even to reversal of RYGB...
August 30, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28840014/cardiovascular-benefits-of-the-newer-medications-for-treating-type-2-diabetes-mellitus
#11
REVIEW
Srikanth Yandrapalli, Wilbert S Aronow
Diabetes mellitus is growing in pandemic proportions and is associated with significant morbidity, mortality, and health care expenditure. Type 2 diabetes mellitus (T2DM) is the most common, accounting for about 90-95% of diagnosed diabetes in United States adults. Individuals with T2DM have a 2- to 3-fold increased risk of cardiovascular (CV) events compared with their non-diabetic counterparts, and CV mortality is responsible for around 80% of the mortality in T2DM. Emerging evidence suggest that in T2DM patients, hyperglycemia plays a little role in the progression of CV disease, and metabolic risk factors like insulin resistance, hypertension, obesity, and dyslipidemia are the major culprits in the initiation and progression of CV disease...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28836148/anti-diabetic-actions-of-esculentin-2cha-1-30-and-its-stable-analogues-in-a-diet-induced-model-of-obesity-diabetes
#12
Srividya Vasu, Opeolu O Ojo, R Charlotte Moffett, J Michael Conlon, Peter R Flatt, Yasser H A Abdel-Wahab
Actions of esculentin-2CHa(1-30) (GFSSIFRGVAKFASKGLGKDLAKLGVDLVA) and its analogues, ([D-Arg(7), D-Lys(15), D-Lys(23)]-esculentin-2CHa(1-30) and [Lys(15)-octanoate]-esculentin-2CHa(1-30), were evaluated in high-fat fed NIH Swiss mice with impaired glucose tolerance and insulin resistance. Twice-daily i.p. administration of the esculentin-2CHa(1-30) peptides (75 nmol/kg body weight) or exendin-4 (25 nmol/kg) for 28 days reduced body weight, without altering cumulative energy intake. All peptides reduced blood glucose levels by 6-12 mmol/l concomitant with lower plasma insulin levels, with significance evident from day 6...
August 23, 2017: Amino Acids
https://www.readbyqxmd.com/read/28822994/glucagon-like-peptide-1-receptor-agonist-stimulates-mitochondrial-bioenergetics-in-human-adipocytes
#13
Joanna Góralska, Agnieszka Śliwa, Anna Gruca, Urszula Raźny, Monika Chojnacka, Anna Polus, Bogdan Solnica, Małgorzata Malczewska-Malec
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28808865/glucagon-like-peptides-1-and-2-are-involved-in-satiety-modulation-after-modified-biliopancreatic-diversion-results-of-a-pilot-study
#14
Everton Cazzo, José Carlos Pareja, Elinton Adami Chaim, Cláudio Saddy Rodrigues Coy, Daniéla Oliveira Magro
BACKGROUND: This paper aimed to evaluate the influence of modified biliopancreatic diversion (BPD) on the levels of GLP-1 and GLP-2 and correlate them with satiety regulation. METHODS: This is a pilot prospective cohort study that evaluated six mildly obese individuals with type 2 diabetes mellitus, which underwent modified BPD and were followed-up for 12 months. Levels of GLP-1 and GLP-2 after a standard meal tolerance test were determined and correlated with satiety scores obtained by means of a visual analogue scale (VAS)...
August 14, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28803984/canagliflozin-potentiates-glp-1-secretion-and-lowers-the-peak-of-gip-secretion-in-rats-fed-a-high-fat-high-sucrose-diet
#15
Tohru Hira, Toshiki Koga, Kazuyo Sasaki, Hiroshi Hara
The glucose-induced secretion of incretins, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), is dependent on luminal glucose levels and transport of glucose via the sodium-glucose transporter 1 (SGLT1) in the small intestine. Because GLP-1 and GIP function in decreasing and increasing the body weight, respectively, we aimed to analyze the effect of transient inhibition of SGLT1 by canagliflozin on incretin secretion in an obese rat model. Male Sprague-Dawley rats were maintained on a high-fat high-sucrose diet for 6-7 weeks, and plasma GLP-1 and GIP levels were measured during an oral glucose tolerance test (OGTT)...
October 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#16
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28792489/l-phenylalanine-modulates-gut-hormone-release-and-glucose-tolerance-and-suppresses-food-intake-through-the-calcium-sensing-receptor-in-rodents
#17
A Alamshah, E Spreckley, M Norton, J S Kinsey-Jones, A Amin, A Ramgulam, Y Cao, R Johnson, K Saleh, E Akalestou, Z Malik, N Gonzalez-Abuin, A Jomard, R Amarsi, A Moolla, P R Sargent, G W Gray, S R Bloom, K G Murphy
OBJECTIVE: High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. METHODS: We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo...
July 13, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28777946/engineered-epidermal-progenitor-cells-can-correct-diet-induced-obesity-and-diabetes
#18
Jiping Yue, Xuewen Gou, Yuanyuan Li, Barton Wicksteed, Xiaoyang Wu
Somatic gene therapy is a promising approach for treating otherwise terminal or debilitating diseases. The human skin is a promising conduit for genetic engineering, as it is the largest and most accessible organ, epidermal autografts and tissue-engineered skin equivalents have been successfully deployed in clinical applications, and skin epidermal stem/progenitor cells for generating such grafts are easy to obtain and expand in vitro. Here, we develop skin grafts from mouse and human epidermal progenitors that were engineered by CRISPR-mediated genome editing to controllably release GLP-1 (glucagon-like peptide 1), a critical incretin that regulates blood glucose homeostasis...
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28777938/engineering-skin-with-skinny-genes
#19
Anika Böttcher, Heiko Lickert, Matthias Tschöp
The increasing prevalence of obesity and diabetes is an urgent worldwide health challenge. Now in Cell Stem Cell, Yue et al. (2017) report a proof-of-concept study using genetically engineered skin transplants that produce the incretin GLP-1 to prevent diet-induced obesity, suggesting a powerful approach for treating metabolic disorders.
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28776152/glucose-metabolism-parameters-and-post-prandial-glp-1-and-glp-2-release-largely-vary-in-several-distinct-situations-a-controlled-comparison-among-individuals-with-crohn-s-disease-and-individuals-with-obesity-before-and-after-bariatric-surgery
#20
Daniéla Oliveira Magro, Everton Cazzo, Paulo Gustavo Kotze, Ana Carolina Junqueira Vasques, Carlos Augusto Real Martinez, Elinton Adami Chaim, Bruno Geloneze, José Carlos Pareja, Cláudio Saddy Rodrigues Coy
BACKGROUND: This study aims to compare the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 among individuals with Crohn's disease (CD), obese individuals before and after bariatric surgery, and healthy controls. METHODS: This an exploratory cross-sectional study that involved five groups of patients (two groups of individuals with CD-active and inactive), bariatric patients (pre- and post-surgery, who were their own controls), and a distinct separated control group of healthy volunteers...
August 3, 2017: Obesity Surgery
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