scholarly journals Combination Therapy with Amylin and Peptide YY[3–36] in Obese Rodents: Anorexigenic Synergy and Weight Loss Additivity

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 6054-6061 ◽  
Author(s):  
Jonathan D. Roth ◽  
Todd Coffey ◽  
Carolyn M. Jodka ◽  
Holly Maier ◽  
Jennifer R. Athanacio ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Peptide Yy ◽  
Peptide Hormone ◽  
Short Term ◽  
Subcutaneous Infusion ◽  
Body Weight Reduction ◽  
Diet Induced Obesity ◽  
Circulating Levels

Circulating levels of the pancreatic β-cell peptide hormone amylin and the gut peptide PYY[3–36] increase after nutrient ingestion. Both have been implicated as short-term signals of meal termination with anorexigenic and weight-reducing effects. However, their combined effects are unknown. We report that the combination of amylin and PYY[3–36] elicited greater anorexigenic and weight-reducing effects than either peptide alone. In high-fat-fed rats, a single ip injection of amylin (10 μg/kg) plus PYY[3–36] (1000 μg/kg) reduced food intake for 24 h (P < 0.05 vs. vehicle), whereas the anorexigenic effects of either PYY[3–36] or amylin alone began to diminish 6 h after injection. These anorexigenic effects were dissociable from changes in locomotor activity. Subcutaneous infusion of amylin plus PYY[3–36] for 14 d suppressed food intake and body weight to a greater extent than either agent alone in both rat and mouse diet-induced obesity (DIO) models (P < 0.05). In DIO-prone rats, 24-h metabolic rate was maintained despite weight loss, and amylin plus PYY[3–36] (but not monotherapy) increased 24-h fat oxidation (P < 0.05 vs. vehicle). Finally, a 4 × 3 factorial design was used to formally describe the interaction between amylin and PYY[3–36]. DIO-prone rats were treated with amylin (0, 4, 20, and 100 μg/kg·d) and PYY[3–36] (0, 200, 400 μg/kg·d) alone and in combination for 14 d. Statistical analyses revealed that food intake suppression with amylin plus PYY[3–36] treatment was synergistic, whereas body weight reduction was additive. Collectively, these observations highlight the importance of studying peptide hormones in combination and suggest that integrated neurohormonal approaches may hold promise as treatments for obesity.

Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice

2012 ◽  
Vol 302 (8) ◽  
pp. E924-E931 ◽  
Author(s):  
Toru Kusakabe ◽  
Ken Ebihara ◽  
Takeru Sakai ◽  
Licht Miyamoto ◽  
Daisuke Aotani ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Food Intake ◽  
Calorie Restriction ◽  
Tolerance Test ◽  
Body Weight Reduction ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Antidiabetic Treatment ◽  
Triglyceride Content

Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic β-cell-derived hormone, was shown to restore a weight-reducing effect of leptin in leptin-resistant diet-induced obesity. However, whether amylin improves the effect of leptin on insulin sensitivity in diet-induced obesity is unclear. Diet-induced obese (DIO) mice were infused with either saline (S), leptin (L; 500 μg·kg−1·day−1), amylin (A; 100 μg·kg−1·day−1), or leptin plus amylin (L/A) for 14 days using osmotic minipumps. Food intake, body weight, metabolic parameters, tissue triglyceride content, and AMP-activated protein kinase (AMPK) activity were examined. Pair-feeding and weight-matched calorie restriction experiments were performed to assess the influence of food intake and body weight reduction. Continuous L/A coadministration significantly reduced food intake, increased energy expenditure, and reduced body weight, whereas administration of L or A alone had no effects. L/A coadministration did not affect blood glucose levels during ad libitum feeding but decreased plasma insulin levels significantly (by 48%), suggesting the enhancement of insulin sensitivity. Insulin tolerance test actually showed the increased effect of insulin in L/A-treated mice. In addition, L/A coadministration significantly decreased tissue triglyceride content and increased AMPKα2 activity in skeletal muscle (by 67%). L/A coadministration enhanced insulin sensitivity more than pair-feeding and weight-matched calorie restriction. In conclusion, this study demonstrates the beneficial effect of L/A coadministration on glucose and lipid metabolism in DIO mice, indicating the possible clinical usefulness of L/A coadministration as a new antidiabetic treatment in obesity-associated diabetes.

scholarly journals Energy Intake of Men With Excess Weight During Normobaric Hypoxic Confinement

2022 ◽  
Vol 12 ◽  
Author(s):  
Igor B. Mekjavic ◽  
Mojca Amon ◽  
Elizabeth J. Simpson ◽  
Roger Kölegård ◽  
Ola Eiken ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Energy Intake ◽  
Weight Reduction ◽  
Peptide Yy ◽  
Normobaric Hypoxia ◽  
Excess Weight ◽  
Postprandial Blood Glucose ◽  
Simulated Altitude ◽  
Body Weight Reduction

Due to the observations of weight loss at high altitude, normobaric hypoxia has been considered as a method of weight loss in obese individuals. With this regard, the aim of the present study was to determine the effect of hypoxia per se on metabolism in men with excess weight. Eight men living with excess weight (125.0 ± 17.7 kg; 30.5 ± 11.1 years, BMI: 37.6 ± 6.2 kg⋅m–2) participated in a randomized cross-over study comprising two 10-day confinements: normobaric (altitude of facility ≃ 940 m) normoxia (NORMOXIA; PIO2 = 133 mmHg), and normobaric hypoxia (HYPOXIA). The PIO2 in the latter was reduced from 105 (simulated altitude of 2,800 m) to 98 mmHg (simulated altitude of 3,400 m over 10 days. Before, and at the end of each confinement, participants completed a meal tolerance test (MTT). Resting energy expenditure (REE), circulating glucose, GLP-1, insulin, catecholamines, ghrelin, peptide-YY (PYY), leptin, gastro-intestinal blood flow, and appetite sensations were measured in fasted and postprandial states. Fasting REE increased after HYPOXIA (+358.0 ± 49.3 kcal⋅day–1, p = 0.03), but not after NORMOXIA (−33.1 ± 17.6 kcal⋅day–1). Postprandial REE was also significantly increased after HYPOXIA (p ≤ 0.05), as was the level of PYY. Furthermore, a tendency for decreased energy intake was concomitant with a significant body weight reduction after HYPOXIA (−0.7 ± 0.2 kg) compared to NORMOXIA (+1.0 ± 0.2 kg). The HYPOXIA trial increased the metabolic requirements, with a tendency toward decreased energy intake concomitant with increased PYY levels supporting the notion of a hypoxia-induced appetite inhibition, that could potentially lead to body weight reduction. The greater postprandial blood-glucose response following hypoxic confinement, suggests the potential development of insulin resistance.

scholarly journals Amylin-Mediated Restoration of Leptin Responsiveness in Diet-Induced Obesity: Magnitude and Mechanisms

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5679-5687 ◽  
Author(s):  
James L. Trevaskis ◽  
Todd Coffey ◽  
Rebecca Cole ◽  
Chunli Lei ◽  
Carrie Wittmer ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Combination Treatment ◽  
Body Weight Loss ◽  
Metabolic Effects ◽  
Fat Utilization ◽  
Diet Induced Obesity ◽  
Expression Of Genes ◽  
Obese Rats

Previously, we reported that combination treatment with rat amylin (100 μg/kg·d) and murine leptin (500 μg/kg·d) elicited greater inhibition of food intake and greater body weight loss in diet-induced obese rats than predicted by the sum of the monotherapy conditions, a finding consistent with amylin-induced restoration of leptin responsiveness. In the present study, a 3 × 4 factorial design was used to formally test for a synergistic interaction, using lower dose ranges of amylin (0, 10, and 50 μg/kg·d) and leptin (0, 5, 25, and 125 μg/kg·d), on food intake and body weight after 4 wk continuous infusion. Response surface methodology analysis revealed significant synergistic anorexigenic (P < 0.05) and body weight-lowering (P < 0.05) effects of amylin/leptin combination treatment, with up to 15% weight loss at doses considerably lower than previously reported. Pair-feeding (PF) experiments demonstrated that reduction of food intake was the predominant mechanism for amylin/leptin-mediated weight loss. However, fat loss was 2-fold greater in amylin/leptin-treated rats than PF controls. Furthermore, amylin/leptin-mediated weight loss was not accompanied by the counterregulatory decrease in energy expenditure and chronic shift toward carbohydrate (rather than fat) utilization observed with PF. Hepatic gene expression analyses revealed that 28 d treatment with amylin/leptin (but not PF) was associated with reduced expression of genes involved in hepatic lipogenesis (Scd1 and Fasn mRNA) and increased expression of genes involved in lipid utilization (Pck1 mRNA). We conclude that amylin/leptin interact synergistically to reduce body weight and adiposity in diet-induced obese rodents through a number of anorexigenic and metabolic effects.

scholarly journals Short-Term Results Suggest That Sleeved Stomach without Resection Is as Effective as Sleeve Gastrectomy in Improving Glucose Control in Type 2 Diabetes Mellitus Sprague-Dawley Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Wenzhuo Zhang ◽  
Jason Widjaja ◽  
Libin Yao ◽  
Yong Shao ◽  
Xiaocheng Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Sleeve Gastrectomy ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Glucose Control ◽  
Sprague Dawley ◽  
Short Term

Background. Although sleeve gastrectomy results in good weight loss and metabolic improvements, it is an irreversible procedure. Therefore, we attempted to assess the possibility of creating a sleeved stomach without resection. Material and Methods. A total of 22 male Sprague-Dawley rats with type 2 diabetes were randomly assigned into 3 different groups: (1) sleeve gastroplasty with gastric remnant-jejunal anastomosis (SGP, n=8); (2) sleeve gastrectomy (SG, n=8); and (3) SHAM (n=6). Body weight, food intake, fasting blood glucose (FBG), hormonal analysis, and oral glucose tolerance test (OGTT) were performed and measured preoperatively and postoperatively. Results. During the postoperative period, SGP and SG showed significantly lower food intake and body weight when compared with the preoperative levels, respectively (p value < 0.05). Postoperatively, SGP and SG showed improvements in FBG and glucose tolerance levels compared to their respective preoperative levels (p<0.05). FBG and glucose tolerance levels did not differ between SGP and SG postoperatively. SG resulted in a reduction in fasting ghrelin levels when compared with the preoperative level (p<0.05). Fasting insulin levels did not differ preoperatively and postoperatively among all groups. Postoperatively, fasting GLP-1 levels were higher in SGP and SG when compared with the preoperative levels, but no statistical significance was observed. Compared preoperatively, the SGP and SG procedures resulted in a decline in HOMA-IR at postoperative 6th week (p<0.05). Conclusion. Our animal experiment suggested that at least in the short term, sleeved stomach without resection resulted in similar weight loss and improved glucose control effects compared to sleeve gastrectomy.

scholarly journals The dual amylin and calcitonin receptor agonist KBP-089 and the GLP-1 receptor agonist liraglutide act complimentarily on body weight reduction and metabolic profile

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anna Thorsø Larsen ◽  
Sofie Gydesen ◽  
Nina Sonne ◽  
Morten Asser Karsdal ◽  
Kim Henriksen
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Gastric Emptying ◽  
Food Intake ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Weight Reduction ◽  
Receptor Agonist ◽  
Calcitonin Receptor ◽  
Body Weight Reduction

Abstract Background Weight loss therapy is becoming more and more important, and two classes of molecules, namely amylin receptor and GLP-1 receptor agonists, have shown promise in this regard. Interestingly, these molecules have several overlapping pharmacological effects, such as suppression of gastric emptying, reduction of glucagon secretion and weight loss in common; however, they also have distinct effects on prandial insulin secretion. Hence, a combination of these two mechanisms is of significant interest. Methods In this study, we investigated the add-on potential of the dual amylin and calcitonin receptor agonist (DACRA) KBP-089 in combination with the GLP-1 receptor agonist liraglutide as obesity treatment in high-fat diet (HFD) fed rats. Results Increasing doses of KBP-089 and liraglutide alone and in combination were studied with respect to their effects on body weight, food intake and glucose metabolism during a 9-week intervention study conducted in HFD rats. Further, the gastric emptying rate during an oral glucose tolerance was assessed. Treatment with KBP-089 and liraglutide dose-dependently lowered body weight 15% (at 2.5 μg/kg/day) and 7% (at 400 μg/kg/day) in HFD rats, respectively, while the combination resulted in a 21% body weight reduction, which was mirrored by reduction in fat depot sizes. Gastric emptying and glucose metabolism were improved, primarily by KBP-089, although liraglutide led to a reduction in fasting plasma glucagon. Conclusion DACRAs complement GLP-1 on food intake, body weight, and glucose tolerance indicating the potential for an add-on therapy.

scholarly journals IQP-VV-102, a Novel Proprietary Composition for Weight Reduction: A Double-Blind Randomized Clinical Trial for Evaluation of Efficacy and Safety

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Barbara Grube ◽  
Udo Bongartz ◽  
Felix Alt
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Weight Reduction ◽  
Short Term ◽  
Double Blind ◽  
Efficacy Analysis ◽  
Body Weight Reduction ◽  
Obese Subjects ◽  
The Individual ◽  
Primary Efficacy Analysis

The individual ingredients in IQP-VV-102 have demonstrated promising effects in reducing sugar and starch digestion, which potentially leads to weight loss. The trial objective was to evaluate the safety and efficacy of IQP-VV-102 in reducing body weight in overweight and obese subjects. 120 overweight and obese individuals aged 18 to 60 years were randomly assigned to 2 treatment arms (IQP-VV-102 and placebo). The trial was conducted in 2 study centres in Berlin, Germany. The primary efficacy analysis was conducted on 117 subjects (IQP-VV-102:N=54; placebo:N=59), comparing the weight loss effect at baseline and 12 weeks after randomization. There was a statistically significant reduction in mean body weight of 3.29 kg (SD 2.30) in the IQP-VV-102 group compared to 0.83 kg (SD 2.00) in the placebo groupp<0.001. There were no serious or product-related adverse events that were reported over the combined period of 14 weeks. The findings suggested that IQP-VV-102 is effective and safe in body weight reduction in overweight and obese individuals in the short term. The study is registered under clinicaltrials.gov asNCT01681069.

scholarly journals The Dual Amylin and Calcitonin Receptor Agonist KBP-089 and the GLP-1 receptor agonist liraglutide act complimentarily on body weight reduction and metabolic profile 

2020 ◽  
Author(s):  
Anna Thorsø Larsen ◽  
Sofie Gydesen ◽  
Nina Sonne ◽  
Morten Asser Karsdal ◽  
Kim Henriksen
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Gastric Emptying ◽  
Food Intake ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Weight Reduction ◽  
Receptor Agonist ◽  
Calcitonin Receptor ◽  
Body Weight Reduction

Abstract Background: Weight loss therapy is becoming more and more important, and two classes of molecules, namely amylin receptor and GLP-1 receptor agonists, have shown promise in this regard. Interestingly, these molecules have several overlapping pharmacological effects, such as suppression of gastric emptying, reduction of glucagon secretion and weight loss in common; however, they also have distinct effects on prandial insulin secretion. Hence, a combination of these two mechanisms is of significant interest. Methods: In this study, we investigated the add-on potential of the dual amylin and calcitonin receptor agonist (DACRA) KBP-089 in combination with the GLP-1 receptor agonist liraglutide as obesity treatment in high-fat diet (HFD) fed rats. Results: Increasing doses of KBP-089 and liraglutide alone and in combination were studied with respect to their effects on body weight, food intake and glucose metabolism during a 9-week intervention study conducted in HFD rats. Further, the gastric emptying rate during an oral glucose tolerance was assessed. Treatment with KBP-089 and liraglutide dose-dependently lowered body weight 15% (at 2.5 µg/kg/day) and 7% (at 400 µg/kg/day) in HFD rats, respectively, while the combination resulted in a 21% body weight reduction, which was mirrored by reduction in fat depot sizes. Gastric emptying and glucose metabolism were improved, primarily by KBP-089, although liraglutide led to a reduction in fasting plasma glucagon. Conclusion: DACRAs complement GLP-1 on food intake, body weight, and glucose tolerance indicating the potential for an add-on therapy.

scholarly journals The dual amylin and calcitonin receptor agonist KBP-089 and the GLP-1 receptor agonist liraglutide act complimentarily on body weight reduction and metabolic profile

2021 ◽  
Author(s):  
Anna Thorsø Larsen ◽  
Sofie Gydesen ◽  
Nina Sonne ◽  
Morten Asser Karsdal ◽  
Kim Henriksen
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Gastric Emptying ◽  
Food Intake ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Weight Reduction ◽  
Receptor Agonist ◽  
Calcitonin Receptor ◽  
Body Weight Reduction

Abstract Background: Weight loss therapy is becoming more and more important, and two classes of molecules, namely amylin receptor and GLP-1 receptor agonists, have shown promise in this regard. Interestingly, these molecules have several overlapping pharmacological effects, such as suppression of gastric emptying, reduction of glucagon secretion and weight loss in common; however, they also have distinct effects on prandial insulin secretion. Hence, a combination of these two mechanisms is of significant interest. Methods: In this study, we investigated the add-on potential of the dual amylin and calcitonin receptor agonist (DACRA) KBP-089 in combination with the GLP-1 receptor agonist liraglutide as obesity treatment in high-fat diet (HFD) fed rats. Results: Increasing doses of KBP-089 and liraglutide alone and in combination were studied with respect to their effects on body weight, food intake and glucose metabolism during a 9-week intervention study conducted in HFD rats. Further, the gastric emptying rate during an oral glucose tolerance was assessed. Treatment with KBP-089 and liraglutide dose-dependently lowered body weight 15% (at 2.5 µg/kg/day) and 7% (at 400 µg/kg/day) in HFD rats, respectively, while the combination resulted in a 21% body weight reduction, which was mirrored by reduction in fat depot sizes. Gastric emptying and glucose metabolism were improved, primarily by KBP-089, although liraglutide led to a reduction in fasting plasma glucagon. Conclusion: DACRAs complement GLP-1 on food intake, body weight, and glucose tolerance indicating the potential for an add-on therapy.

scholarly journals Effects of Dietary Butyrate on Diet-Induced Obesity and Lipid Metabolism

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 525-525
Author(s):  
Jinyoung Shon ◽  
Yoon Jung Park
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Food Intake ◽  
Sodium Butyrate ◽  
High Fat Diet ◽  
High Fat ◽  
Short Term ◽  
Acid Receptor ◽  
Ppar Γ ◽  
Diet Induced Obesity

Abstract Objectives We examined the effects of dietary butyrate, a short-chain fatty acids (SCFAs) on body weight control and metabolism in a diet-induced obesity rat model. Methods Male Sprague-Dawley rats fed with high-fat diet for 14 weeks. Sodium butyrate was administrated through diet supplementation at 3% wt/wt for long-term (14 weeks) or drinking water at 1% for short-term (2 weeks). Serum and feces were collected. Colon and liver tissues used for analyzing mRNA expression. To assess the effects of butyrate on lipid metabolism, 3T3-L1 cells were treated with sodium butyrate and sodium-3-hyroxybutyrate during adipogenic differentiation. Results On the high-fat diet, dietary supplementation of butyrate protected against body weight gain. Interestingly, food intake was increased and consistently colonic Proglucagon (Gcg), encoding Glucagon-like Peptide-1 (GLP-1) involved in appetite-suppression, was decreased. In contrast, short-term administration of butyrate did not affect body weight and food intake. Free fatty acid receptor 2 (Ffar2), a G-protein coupled receptor recognizing SCFAs and stimulating GLP-1 production, was decreased in colon. The colonic Hydroxycarboxylic acid receptor 2 (Hcar2) and Tight junction protein-1 (Tjp1) marginally increased but expression of inflammatory cytokines was not altered, implicating that anti-obesity effects of butyrate were not primarily through colon. In the liver, butyrate showed significantly decreased Ffar2 and Peroxisome proliferator–activated receptor-γ (Ppar-γ). In the butyrate group, aberrant phenotypes were observed including hyperlipidemia and alteration of serum level of adiponectin without change in fecal energy density. Intriguingly, in the 3T3-L1 cell line, fat accumulation was significantly stimulated at lower concentration of butyrate with elevated expression of Ffar2 and Ppar-γ. High concentration of butyrate reduced Ffar2 and Ppar-γ and suppressed adipocytic fat accumulation. Conclusions Our results suggested that dietary butyrate prevented diet-induced obesity despite increased food intake. Moreover, butyrate may regulate lipid metabolism in a dose-dependent manner. Funding Sources This research was supported by Basic Science Research Program through the NRF funded by the Ministry of Education. J.S is grateful for financial support from Hyundai Motor Chung Mong-Koo Foundation.

scholarly journals The dual amylin and calcitonin receptor agonist KBP-089 and the GLP-1 receptor agonist liraglutide act complimentarily on body weight reduction and metabolic profile

2020 ◽  
Author(s):  
Anna Thorsø Larsen ◽  
Sofie Gydesen ◽  
Nina Sonne ◽  
Morten Asser Karsdal ◽  
Kim Henriksen
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Gastric Emptying ◽  
Food Intake ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Weight Reduction ◽  
Receptor Agonist ◽  
Calcitonin Receptor ◽  
Body Weight Reduction

Abstract Background Weight loss therapy is becoming more and more important, and two classes of molecules, namely amylin receptor and GLP-1 receptor agonists, have shown promise in this regard. Interestingly, these molecules have several overlapping pharmacological effects, such as suppression of gastric emptying, reduction of glucagon secretion and weight loss in common; however, they also have distinct effects on prandial insulin secretion. Hence, a combination of these two mechanisms is of significant interest. Methods In this study, we investigated the add-on potential of the dual amylin and calcitonin receptor agonist (DACRA) KBP-089 in combination with the GLP-1 receptor agonist liraglutide as obesity treatment in high-fat diet (HFD) fed rats. Results Increasing doses of KBP-089 and liraglutide alone and in combination were studied with respect to their effects on body weight, food intake and glucose metabolism during a 9-week intervention study conducted in HFD rats. Further, the gastric emptying rate during an oral glucose tolerance was assessed. Treatment with KBP-089 and liraglutide dose-dependently lowered body weight 15% (at 2.5 µg/kg/day) and 7% (at 400 µg/kg/day) in HFD rats, respectively, while the combination resulted in a 21% body weight reduction, which was mirrored by reduction in fat depot sizes. Gastric emptying and glucose metabolism were improved, primarily by KBP-089, although liraglutide led to a reduction in fasting plasma glucagon. Conclusion DACRAs complement GLP-1 on food intake, body weight, and glucose tolerance indicating the potential for an add-on therapy.

Sign in / Sign up

Export Citation Format

Share Document