Efficacy of exogenous recombinant murine leptin in lean and obese 10- to 12-mo-old female CD-1 mice

1998 ◽  
Vol 275 (4) ◽  
pp. R950-R959 ◽  
Author(s):  
Mary Ann Pelleymounter ◽  
Mary Jane Cullen ◽  
Denis Healy ◽  
Randy Hecht ◽  
Dwight Winters ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Obese Mice ◽  
Appetite Suppression ◽  
Specific Effects ◽  
Leptin Sensitivity ◽  
Fat Reduction ◽  
Body Weights ◽  
High Doses ◽  
The Right

Leptin efficacy was compared in obese and lean female CD-1 mice. Body weights in these 10- to 12-mo-old mice ranged from 29.7 to 62.0 g, and leptin levels correlated with body weight. Mice from the lean and obese ends of the weight distribution were treated with daily peripheral leptin injections (1–100 mg/kg) for a 33-day period. The half-maximal effective doses for weight loss and fat reduction were shifted 0.5–0.7 log to the right for obese mice. Leptin was less efficacious at low doses (1–3 mg/kg) in obese mice but equal to or more efficacious in obese than lean mice at high doses (30–100 mg/kg). Leptin’s initial effects on weight loss could be explained by appetite suppression in both groups, but its effects on fat reduction were greater in leptin-treated than pair-fed mice, particularly in the lean group. Leptin also prevented the elevations in serum corticosterone and ketones found in pair-fed lean mice. These data allow a quantitative comparison of leptin sensitivity in obese vs. lean CD-1 mice and suggest that in mice where obesity is a function of outbreeding and age, leptin sensitivity is moderately reduced. Furthermore, although appetite suppression has a clear role in leptin’s effects on body weight, leptin may also have specific effects on lipid metabolism and mobilization that are different from the metabolic compensations that normally occur with food deprivation.

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

Effect of Changes in Ambient Temperature on Spontaneous Activity, Food Intake and Body Weight of Goldthioglucose-Obese and Nonobese Mice

1957 ◽  
Vol 188 (3) ◽  
pp. 435-438 ◽  
Author(s):  
M. J. Fregly ◽  
N. B. Marshall ◽  
J. Mayer
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Ambient Temperature ◽  
The Body ◽  
Lower Body ◽  
Obese Mice ◽  
Ambient Temperatures ◽  
Exposure To Cold ◽  
Running Activity ◽  
Body Weights

Goldthioglucose-obese mice cannot adjust their food intake to meet the increased energy requirements due to cold. At all ambient temperatures above 15°C the spontaneous running activity of these animals is less than that observed for nonobese controls. Activity of obese mice is maximal at 19°C and minimal at 15°C or lower. Body weights decrease during exposure to cold. In contrast to that of obese mice, running activity of nonobese controls is maximal at an ambient temperature of 25°C but nearly ceases at 15°C or lower. The food intake of these animals increases in the cold and remains elevated even at temperatures at which activity decreases. The body weight of nonobese controls is either maintained constant or increases during exposure to cold air.

scholarly journals 1343. Prophylactic Dosing of Baloxavir Acid Eliminates Mortality in Mice Lethal Influenza A Virus Infection Model

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S410-S411
Author(s):  
Shinya Shano ◽  
Keita Fukao ◽  
Takeshi Noshi ◽  
Kenji Sato ◽  
Masashi Sakuramoto ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Lethal Dose ◽  
Body Weight Loss ◽  
Prophylactic Efficacy ◽  
Body Weights ◽  
Single Dosing

Abstract Background Baloxavir acid (BXA), an active form of orally available prodrug baloxavir marboxil (BXM, formerly S-033188), is a novel small molecule inhibitor of cap-dependent endonuclease (CEN) of influenza A and B virus, and was recently launched for the treatment of acute and uncomplicated influenza with single dosing of BXM (the trade name XOFLUZA™) in Japan in March 2018. Here, we evaluated the prophylactic efficacy of BXA in mice lethally infected with influenza A virus. Methods T1/2 of BXA in human is more than 10 times longer than that in mice. Therefore, suspension of BXA was subcutaneously administered at 0.8 or 1.6 mg/kg in mice to maintain the plasma concentration of BXA as seen in humans, and then mice were intranasally inoculated with a lethal dose of A/PR/8/34 strain at 48, 72, or 96 hours after the administration of BXA. Survival time and body weight change were then monitored through a 28-day period after virus infection. Mice were euthanized and regarded as dead if their body weights were lower than 70% of the initial body weights according to humane endpoints. Results Single dosing of BXA (1.6 mg/kg) completely eliminated mortality in mice, when the mice were administrated the drug at 48, 72, or 96 hours before virus infection (Figure 1). BXA treatment also significantly prevented body weight loss, consistent with the prolonged survival. Conclusion Prophylactic dosing of BXA exhibited significant protective efficacy against mortality and body weight loss in mice following a lethal infection with influenza A virus. The significant prophylactic efficacy observed in our mouse model suggests the potential utility of BXM for the prophylaxis of influenza in human. Disclosures S. Shano, Shionogi & Co., Ltd.: Employee, Salary. K. Fukao, Shionogi & Co., Ltd.: Employee, Salary. T. Noshi, Shionogi & Co., Ltd.: Employee, Salary. K. Sato, Shionogi & Co., Ltd.: Employee, Salary. M. Sakuramoto, Shionogi & Co., Ltd.: Employee, Salary. K. Baba, Shionogi TechnoAdvance Research & Co., Ltd.: Employee, Salary. T. Shishido, Shionogi & Co., Ltd.: Employee, Salary. A. Naito, Shionogi & Co., Ltd.: Employee, Salary.

scholarly journals OR28-5 Bile Acid Sequestration Accelerates Glucagon Receptor-Mediated Body Weight Loss in Obese Mice

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Teayoun Kim ◽  
Shelly Nason ◽  
Jessica Antipenko ◽  
Natalie Presedo ◽  
Brian Finan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Bile Acid ◽  
Body Weight Loss ◽  
Obese Mice ◽  
Glucagon Receptor

Abstract 17023: Adipose Tissue Specific Temporal Deletion of Ager Induces Weight Loss in Diet Induced Obese Mice and Improves Glucose Homeostasis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Robin Wilson ◽  
Lakshmi Arivazhagan ◽  
Henry Ruiz ◽  
Jay Pendse ◽  
Laura Frye ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Adipose Tissue ◽  
Glucose Homeostasis ◽  
Fasting Glucose ◽  
Obese Mice ◽  
Gene Encoding ◽  
Low Fat Diet ◽  
Insulin Tolerance ◽  
Specific Deletion

Introduction: The incidence of obesity and its comorbidities is increasing at an alarming rate in US and around the globe. Our previous studies showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance (IR), as global Ager (gene encoding RAGE) and adipocyte-specific Ager- deleted mice fed a high fat diet (HFD) showed protection from weight gain and IR. However, the role of Ager deletion in mice with established obesity, switched to low fat diet has not been tested. We hypothesize that temporal adipocyte-specific deletion of Ager in obese mice could enhance weight loss and improves glucose homeostasis. Methods: Mice with conditional adipocyte-specific Ager deletion were generated by breeding Ager flox/flox mice with AdipoQ ERT2 Cre recombinase mice resulting in Ager flox/flox / AdipoQ ERT2 Cre (+) and Cre (-) animals. Mice were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity and were then treated with tamoxifen (TAM) (75 mg/kg per day x 3 alternative days) to induce deletion of Ager . After 4 weeks of TAM treatment, mice were switched to standard chow for 7 weeks and body weight was monitored regularly. Fasting glucose, insulin and glucose tolerance was measured. Results: After 7 weeks of switching to standard chow following TAM, Cre (+) lost significantly more body weight whereas Cre (-) mice showed no significant weight loss over 7 weeks. Furthermore, Cre (+) mice exhibited significantly higher food intake, lower fasting glucose, lower epididymal and inguinal white adipose tissue weights, and improved glucose and insulin tolerance compared to Cre (-) mice. Conclusions: Temporal adipocyte-specific deletion of Ager in mice with established obesity promotes weight loss and improves glucose homeostasis. RAGE may act as a novel therapeutic target in obesity.

scholarly journals Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting

1998 ◽  
Vol 274 (6) ◽  
pp. R1518-R1525 ◽  
Author(s):  
Atsushi Kaibara ◽  
Armin Moshyedi ◽  
Troy Auffenberg ◽  
Amer Abouhamze ◽  
Edward M. Copeland ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Protein ◽  
Obese Mice ◽  
Preferential Loss ◽  
Phase Protein ◽  
Protein Response

The ob gene product leptin is known to produce anorexia and loss of body fat when chronically administered to both lean and genetically obese mice. The current study was undertaken to examine whether administration of recombinant leptin in quantities sufficient to produce decreases in food intake and body weight and alterations in body composition would elicit either an hepatic acute phase protein response or preferential loss of carcass lean tissue. Mice were administered increasing quantities of recombinant human leptin or human tumor necrosis factor-α as a positive control. Although leptin (at 10 mg/kg body wt) produced significant anorexia and weight loss (both P < 0.05), human leptin administration did not appear to induce an hepatic acute phase protein response in either lean or genetically obese mice, as determined by protein synthetic rates in the liver or changes in the plasma concentration of the murine acute phase protein reactants, amyloid A, amyloid P, or seromucoid (α1-acid glycoprotein). In addition, human leptin administration did not induce a loss of fat-free dry mass (protein) in lean or obese animals. The findings suggest that at doses adequate to alter food intake and body weight leptin is not a significant inducer of the hepatic acute phase response nor does leptin promote the preferential loss of somatic protein characteristic of a chronic inflammatory process.

Methylnaltrexone potentiates body weight and fat reduction with leptin

2018 ◽  
Vol 5 (6) ◽  
pp. 373-378 ◽  
Author(s):  
Chun-Su Yuan, MD, PhD ◽  
Shi Sun, PhD ◽  
Anoja Attele, MD ◽  
Chong-Zhi Wang, PhD ◽  
Robin Tong, BS ◽  
...  
Keyword(s):  
Body Weight ◽  
Neonatal Rat ◽  
Opioid Antagonist ◽  
Fat Pad ◽  
Reduced Body ◽  
Fat Reduction ◽  
Brown Adipose ◽  
The Right ◽  
Neonatal Rat Model ◽  
Daily Intraperitoneal Injection

Objective: Leptin increases energy expenditure by enhancing systemic and brown adipose metabolism. In a neonatal rat model, retroperitoneal fat pad weight decreased significantly in leptin-treated animals, which reduced body weight. As opioids increase feeding, opioid antagonists may decrease food intake and body weight. However, interactions between leptin and the activity of peripheral opioids on body weight and fat accumulation have not been investigated. In this study, the authors evaluated the effects of naloxone (a nonselective opioid antagonist) and methylnaltrexone (a peripherally acting opioid antagonist) on the action of leptin in neonatal rats.Results: Compared with control, the weight gain of pups given a single daily intraperitoneal injection of leptin 0.5 mg/kg, leptin 0.5 mg/kg plus naloxone 0.3 mg/kg, or leptin 0.5 mg/kg plus methylnaltrexone 3.0 mg/kg for 8 consecutive days was significantly reduced (all p 0.01). Naloxone or methylnaltrexone significantly potentiated leptin’s effect on body weight (p 0.05 or p 0.01, respectively). After coadministration of leptin plus naloxone or leptin plus methylnaltrexone, weight reduction in the right retroperitoneal fat pads was also significant compared with the reduction after leptin alone (p 0.05 or p 0.01, respectively).Conclusions: The data suggest the existence of a peripheral opioid-related mechanism in leptinactive modulation of body weight.

BODY WEIGHT OF PODISUS MACULIVENTRIS (SAY) UNDER VARIOUS FEEDING REGIMENS

1990 ◽  
Vol 122 (2) ◽  
pp. 285-294 ◽  
Author(s):  
Robert J. O’Neil ◽  
Robert N. Wiedenmann
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Weight Change ◽  
Reproductive Effort ◽  
Tenebrio Molitor ◽  
Green Bean ◽  
Podisus Maculiventris ◽  
Agricultural Systems ◽  
Body Weights ◽  
Heteroptera Pentatomidae

AbstractBody weights were measured for Podisus maculiventris (Say) (Heteroptera: Pentatomidae) given low prey inputs. Predators were fed green bean slices ad lib and a single mealworm larva (Tenebrio molitor L.) of one of two size classes, for a 24-h period every 1, 2, 4, 8, or 16 days. Other treatments included predators fed to excess of daily attacks, predators given only green bean slices, and predators given no food. Results showed that predators fed bean slices maintained body weight after an initial decline, whereas predators given no food lost weight continually until death. Predators maintained weight when fed prey ad lib, and when fed prey of either size daily. Those fed at longer intervals lost weight between feedings, and weight fluctuations increased as the interfeeding interval increased. Slopes of weight change between feedings did not differ significantly for predators fed at 2- through 16-day intervals. During oviposition, predators lost about 15 mg of body weight. Egg clutches comprised about 60% of the weight lost. Egg weights did not differ among treatments. The results suggest that P. maculiventris can survive long periods without prey, and adjusts its weight loss by reducing reproductive effort when prey become scarce. The importance of these adaptations for P. maculiventris to sustain populations in agricultural systems is discussed.

Nutritional stress and pre-implantation mortality in Merino sheep, (1964–7). General discussion and conclusions

1970 ◽  
Vol 74 (1) ◽  
pp. 199-204 ◽  
Author(s):  
T. N. Edey
Keyword(s):  
Body Weight ◽  
Left Ovary ◽  
Fertilization Failure ◽  
Normal Length ◽  
Body Weights ◽  
Embryonic Loss ◽  
Long Cycles ◽  
Significant Regression ◽  
The Right ◽  
Embryonic Death

SUMMARYCollation and re-analysis of the results obtained in separate experiments investigating prenatal mortality in Merino ewes over a period of 4 years have made it possible to draw the following general conclusions:Data from the control groups indicated that in 3 out of 4 years basal prenatal loss averaged approximately 25%, which agrees with a number of other estimates in the literature. Higher losses of ova in 1965 than in the other 3 years could not be partitioned accurately between fertilization failure and prenatal mortality.Submaintenance nutrition apparently caused embryo mortality in 1964, and possibly in 1967, when underfeeding from day 7 to 37 was followed by an unusual number of long cycles; however, there was no evidence of increased mortality in 1965 and 1966.Losses of ova shed as twins were significantly greater than amongst those shed as singles in 1964 and 1967. The higher loss of twin ova was clearly associated with the treated groups in 1964.In each of the 4 years the left ovary produced more ova than the right, and when the 4 years' data were combined, survival of ova shed by the left ovary was significantly better than of those shed by the right. The type of twin ovulation, i.e. whether the two ova came from one ovary or two, had no consistent effect on prenatal mortality.In 3 years there was no significant regression of prenatal mortality on body weight at mating. However, in 1965, when body weights were relatively low, there was a significantly negative regression. It is possible that there is a critical body weight below which poorer prenatal survival can be expected.Ewes which suffered embryonic loss followed by a delayed return to service subsequently conceived less readily than those having a cycle of normal length following fertilization failure or early embryonic death. It is postulated that in some cases this may be because ovulation occurs while resorption is still incomplete. For some ewes having long cycles after embryonic death, anoestrus or removal of the fertile rams precluded subsequent conception in that season. This was an added reason for the season's lambing performance of ‘long cycle’ ewes being much worse than that of ewes re-mated after normal length cycles.

scholarly journals Pre-Conception Weight Loss Improves Reproductive, Metabolic and Kidney Health in Obese Mice and Their Offspring

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A322-A323
Author(s):  
Natassia Rodrigo ◽  
Hui Chen ◽  
Carol Pollock ◽  
Sarah Glastras
Keyword(s):  
Chronic Kidney Disease ◽  
Weight Loss ◽  
Body Weight ◽  
Glucose Tolerance ◽  
Inflammatory Markers ◽  
Metabolic Health ◽  
Late Gestation ◽  
Obese Mice ◽  
Rt Pcr ◽  
Metabolic Outcomes

Abstract Background and Aims: An alarming 40% of women of reproductive age have obesity and during pregnancy obesity adversely impacts metabolic health in mothers and offspring. Maternal complications include diabetes, preeclampsia and chronic kidney disease (CKD). Our previous work showed that offspring have increased risks of obesity, diabetes, and CKD. While pre-pregnancy weight optimisation is advocated, evidence of benefits for mother and offspring are lacking. We aimed to determine if weight loss prior to pregnancy, either with diet modification or liraglutide, improves maternal and offspring metabolic outcomes, and reduces kidney complications in obese mothers and the offspring. Methods: C57BL/6 female mice were fed a high-fat-diet (HFD) for 8 weeks and compared to lean chow-fed controls. HFD-fed dams were administered liraglutide (0.3mg/kg, s.c., for 4weeks) or switched to chow, to induce pre-conception weight loss. Pregnancy rates were observed after mating. Maternal anthropometry and glucose tolerance were measured before and after intervention, and at late gestation. Pregnant dams were either culled at gestational day 18–20 with blood and kidney harvested, or allowed to deliver their offspring. Offspring anthropometry, and glucose tolerance were assessed at postnatal week 12 after either HFD or chow feeding. Immunohistochemistry (IHC), western blotting and RT-PCR were used to measure kidney metabolic (FAS, SREBP) and inflammatory markers (CD-68,TGF-b). Results: HFD-fed dams had reduced glucose tolerance compared to chow-fed dams (p&lt;0.0001), and higher expression of renal metabolic and inflammatory markers in late gestation (eg FAS &lt;0.05, TGFb &lt;0.05). Intervention with liraglutide or diet lowered body weight, improving glucose tolerance (both p&lt;0.001), and fecundity. Markers of kidney damage, namely albuminuria and fibronectin (by RT-PCR and IHC) were reduced (both p&lt;0.05). Liraglutide treated mice exhibited greater gestational weight gain than mice switched to chow (P&lt;0.001). Markers of inflammation and oxidative stress were significantly lower in obese mice with preconception weight loss via diet compared to liraglutide (eg. MnSOD, PGC1α p&lt;0.05). The offspring of obese mothers with pre-conception weight loss had lower body weight (p&lt;0.001) and improved glucose tolerance (p&lt;0.01). Kidney metabolic and inflammatory markers (MCP-1, FAS, SREBP, CD68) were significantly altered in HFD-fed offspring of obese mothers administered liraglutide pre pregnancy (p&lt;0.05). Conclusions: Preconception weight loss improves fertility, weight and metabolic outcomes in mothers and the offspring, with benefits on reproduction, metabolic health, and chronic kidney disease risk. Therefore, obese women should be targeted for pre-conception weight loss to improve intergenerational metabolic health.

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