Discovery of 1-(2,4-Dichlorophenyl)-N-(piperidin-1-yl)-4-((pyrrolidine-1-sulfonamido)methyl)-5-(5-((4-(trifluoromethyl)phenyl)ethynyl)thiophene-2-yl)-1H-pyrazole-3-carboxamide as a Novel Peripherally Restricted Cannabinoid-1 Receptor Antagonist with Significant Weight-Loss Efficacy in Diet-Induced Obese Mice

2013 ◽  
Vol 56 (24) ◽  
pp. 9920-9933 ◽  
Author(s):  
Chun-Ping Chang ◽  
Chien-Huang Wu ◽  
Jen-Shin Song ◽  
Ming-Chen Chou ◽  
Ying-Chieh Wong ◽  
...  
Keyword(s):  
Weight Loss ◽  
Receptor Antagonist ◽  
Obese Mice ◽  
Significant Weight Loss ◽  
Cannabinoid 1 Receptor

scholarly journals Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation without Significant Weight Loss in Obese Mice with Non-Alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (23) ◽  
pp. 9156
Author(s):  
Rachel B. Wilson ◽  
Richard Zhang ◽  
Yun Jin Chen ◽  
Kia M. Peters ◽  
Cynthia G. Sawyez ◽  
...  
Keyword(s):  
Weight Loss ◽  
Fatty Liver Disease ◽  
Restricted Feeding ◽  
Liver Inflammation ◽  
Obese Mice ◽  
Significant Weight Loss ◽  
Short Term ◽  
Alcoholic Fatty Liver ◽  
Ad Libitum ◽  
Alcoholic Fatty Liver Disease

Prolonged, isocaloric, time-restricted feeding (TRF) protocols can promote weight loss, improve metabolic dysregulation, and mitigate non-alcoholic fatty liver disease (NAFLD). In addition, 3-day, severe caloric restriction can improve liver metabolism and glucose homeostasis prior to significant weight loss. Thus, we hypothesized that short-term, isocaloric TRF would improve NAFLD and characteristics of metabolic syndrome in diet-induced obese male mice. After 26 weeks of ad libitum access to western diet, mice either continued feeding ad libitum or were provided with access to the same quantity of western diet for 8 h daily, over the course of two weeks. Remarkably, this short-term TRF protocol modestly decreased liver tissue inflammation in the absence of changes in body weight or epidydimal fat mass. There were no changes in hepatic lipid accumulation or other characteristics of NAFLD. We observed no changes in liver lipid metabolism-related gene expression, despite increased plasma free fatty acids and decreased plasma triglycerides in the TRF group. However, liver Grp78 and Txnip expression were decreased with TRF suggesting hepatic endoplasmic reticulum (ER) stress and activation of inflammatory pathways may have been diminished. We conclude that two-week, isocaloric TRF can potentially decrease liver inflammation, without significant weight loss or reductions in hepatic steatosis, in obese mice with NAFLD.

scholarly journals Emerging drugs for obesity therapy

2009 ◽  
Vol 53 (2) ◽  
pp. 271-280 ◽  
Author(s):  
Maria Teresa Zanella ◽  
Fernando Flexa Ribeiro Filho
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Receptor Antagonist ◽  
Therapeutic Potential ◽  
Lifestyle Changes ◽  
Cannabinoid 1 Receptor ◽  
Obesity Therapy ◽  
Limited Effectiveness ◽  
Long Term Treatment

Central obesity have an important impact on the development of risk factors for coronary heart disease, including dislipidemia, glucose intolerance, insulin resistance and hypertension. These factors contribute to building cardiovascular (CV) disease as a major cause of death. The approach to obesity therapy should be designed to reduce CV risk and mortality. Diet and lifestyle changes remain the cornerstones of therapy for obesity, but the resultant weight loss is often small and long-term success is uncommon and disappointing. Drug therapy is considered for individuals with a body mass index greater than 30 kg/m² or ranging from 25 to 30 kg/m² if they have comorbid conditions. Antiobesity agents can be helpful to some patients in achieving and maintaining meaningful weight loss, but yet our pharmaceutical tools are of limited effectiveness considering the magnitude of the problem. At the present, only two drugs, orlistat and sibutramine, are approved for long-term treatment of obesity and promote no more than 5 to 10% of weight loss. Rimonabant, a cannabinoid-1 receptor antagonist, was withdrawn from the market because of concerns about its safety, including risk of suicidal and seizures, although very effective in promoting clinically meaningful weight loss, reduction in waist circumference, and improvements in several metabolic risk factors, rimonabant, a cannabinoid-1 receptor antagonist was withdrawn from the market because it concerns about its safety, including risk of suicidal and seizures. Fortunately, recent fundamental insights into the neuroendocrine mechanisms regulating body weight provide an expanding list of molecular targets for novel, rationally designed antiobesity drugs. In this review, the therapeutic potential of some antiobesity molecules in the development will be analyzed based on an understanding of energy homeostasis.

Effect of competitive antagonism of NO synthetase on weight and food intake in obese and diabetic mice

1994 ◽  
Vol 266 (1) ◽  
pp. R164-R168 ◽  
Author(s):  
J. E. Morley ◽  
J. F. Flood
Keyword(s):  
Nitric Oxide ◽  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Marked Effect ◽  
Obese Mice ◽  
Significant Weight Loss ◽  
Nitric Oxide Synthetase ◽  
Competitive Antagonism

Recent studies have suggested a role for nitric oxide (NO) in the regulation of food intake. The present studies were undertaken to examine the effects of the administration of a nitric oxide synthetase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on food intake and weight loss. Two genetically obese mice, the ob/ob and db/db strains, and their lean heterozygote littermate controls, ob/c and db/c, served as subjects. In the first experiment, we demonstrated that L-NAME (100 micrograms/kg) given twice over a feeding period of 7 h/day produced a small but significant weight loss in ob/ob mice but not in their lean-genotype controls (P < 0.05). In the second experiment, a higher dose of L-NAME (100 mg/kg), given twice daily, produced a marked effect on body weight, with the ob/ob mice losing approximately 10% of their body weight in 9 days. The ob/c mice showed a lesser decrease in body weight. Food intake was decreased on all 9 days in the ob/ob mice (P < 0.01). A small decrease in body weight and food intake was seen in db/db and db/c mice receiving L-NAME. These studies provide further evidence for a role of nitric oxide in the modulation of food intake and weight gain.

Abstract #615: Hispanic People Achieve Clinically Significant Weight loss with Liraglutide 3.0 Mg for Weight Management

2015 ◽  
Vol 21 ◽  
pp. 121
Author(s):  
Patrick O’Neil ◽  
W. Timothy Garvey ◽  
J. Michael Gonzalez-Campoy ◽  
Pablo Mora ◽  
Rafael Violante Ortiz ◽  
...  
Keyword(s):  
Weight Loss ◽  
Weight Management ◽  
Significant Weight Loss ◽  
Hispanic People ◽  
Clinically Significant

Primary hyperparathyroidism in pregnancy: Uncommon manifestation of significant weight loss

2020 ◽  
Author(s):  
Timea Varga ◽  
Isuri Kurera ◽  
James Clark ◽  
Benjamin Field ◽  
Vidhu Nayyar ◽  
...  
Keyword(s):  
Weight Loss ◽  
Primary Hyperparathyroidism ◽  
Significant Weight Loss ◽  
In Pregnancy

1965-P: Glucagon Receptor Agonism Stimulates Body Weight Loss in Antibiotic Treatment in Obese Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1965-P
Author(s):  
TEAYOUN KIM ◽  
JESSICA P. ANTIPENKO ◽  
SHELLY NASON ◽  
NATALIE PRESEDO ◽  
WILLIAM J. VAN DER POL ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Antibiotic Treatment ◽  
Body Weight Loss ◽  
Obese Mice ◽  
Glucagon Receptor
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