Daily CCK injection enhances reduction of body weight by chronic intracerebroventricular leptin infusion

In the present study, we tested the hypothesis that a single daily injection of the gut peptide CCK, together with continuous leptin infusion, would produce significantly greater loss of body weight than leptin alone. We found that a single daily intraperitoneal injection of CCK-8 (0.5 μg/kg) significantly enhanced the weight-reducing effects of 0.5 μg/day leptin infused continuously into the lateral ventricle of male Sprague-Dawley rats by osmotic minipump. However, CCK and leptin together did not enhance reduction of daily chow intake. Furthermore, there was no synergistic reduction of 30-min sucrose intake, although a significant main effect of both leptin and CCK was observed on sucrose intake. These results 1) confirm our previous reports of synergy between leptin and CCK on body weight, 2) demonstrate that enhancement of leptin-induced weight loss does not require bolus administration of leptin, and 3) suggest that enhanced body weight loss following leptin and CCK does not require synergistic reduction of food intake by leptin and CCK.

Download Full-text

Dietary Exposure to Oxidized Frying Oil from Fetus to Adulthood Suppresses Male Reproductive Development by Altering Testicular Cholesterol and Testosterone Homeostasis in Sprague Dawley Rats

Journal of Nutrition ◽

10.1093/jn/nxaa091 ◽

2020 ◽

Vol 150 (7) ◽

pp. 1713-1721

Author(s):

Hai-Ping Wu ◽

Yu-Shun Lin ◽

Chi-Fen Chang ◽

Shui-Yuan Lu ◽

Pei-Min Chao

Keyword(s):

Weight Loss ◽

Body Weight ◽

Soybean Oil ◽

Body Weight Loss ◽

Reproductive Development ◽

Frying Oil ◽

Female Rats ◽

Male Rats ◽

Sprague Dawley ◽

Sprague Dawley Rats

ABSTRACT Background Dietary frying oil may have endocrine-disrupting effects, as a feminization effect was observed in cohorts of C57BL/6J male mice fetuses from dams consuming oxidized frying oil (OFO) during pregnancy. Objective The aim of present study was to test the hypothesis that OFO is an anti-androgen. Methods In experiment 1, male progeny of Sprague Dawley female rats fed fresh oil or an OFO diet (10 g fat/100 g, from fresh or 24-h–fried soybean oil; [control diet (C) and OFO groups, respectively] from midgestation through lactation were studied. Pups were weaned at 3 wk of age and then consumed their mothers’ diet until 9 wk of age. In addition, a group of dams and pups that consumed a high-fat diet (HF; 10 g fried and 20 g fresh soybean oil/100 g) was included to counteract body-weight loss associated with OFO ingestion. Indices of male reproductive development and testosterone homeostasis were measured. In experiment 2, male rats were allocated to C and OFO groups (treated as above) and indices of male fertility compared at 9–10 wk of age. Results In experiment 1, final body weights of the HF group were lower (17%) than the C group but higher (14%) than the OFO group (P < 0.0001 for each). In addition to abnormalities in seminiferous tubules, HF and OFO groups did not differ from one another, but, compared with the C group, had delayed preputial separation (4.9 d) and reductions in serum testosterone concentrations (17–74%), anogenital distance (8–20%), weights of androgen-dependent tissues (8–30%), testicular testosterone and cholesterol concentrations (30–40%), and mRNA levels of genes involved in steroidogenesis and cholesterol homeostasis (30–70%). In experiment 2, OFO-exposed males had 20% lower sperm motility (P < 0.05); however, when mated to normal females, pregnancy rates and litter sizes did not differ between OFO and C groups. Conclusions The anti-androgenic effect of OFO in Sprague Dawley rats was attributed to decreased testicular concentrations of cholesterol (testosterone precursor) and not body-weight loss.

Download Full-text

Maternal low-protein diet causes body weight loss in male, neonate Sprague–Dawley rats involving UCP-1-mediated thermogenesis

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2015.01.008 ◽

2015 ◽

Vol 26 (7) ◽

pp. 729-735 ◽

Cited By ~ 14

Author(s):

Kate J. Claycombe ◽

Emilie E. Vomhof-DeKrey ◽

James N. Roemmich ◽

Turk Rhen ◽

Othman Ghribi

Keyword(s):

Weight Loss ◽

Body Weight ◽

Body Weight Loss ◽

Protein Diet ◽

Low Protein Diet ◽

Sprague Dawley ◽

Low Protein ◽

Sprague Dawley Rats ◽

Male Neonate

Download Full-text

Maternal low protein diet leads to dysregulation of placental iNKT cells and M1/M2 macrophage ratio, body weight loss in male, neonate Sprague‐Dawley rats and increased UCP‐1 mediated thermogenesis

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.lb257 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

Emilie Vomhof‐DeKrey ◽

James Roemmich ◽

Kate Claycombe

Keyword(s):

Weight Loss ◽

Body Weight ◽

Body Weight Loss ◽

Protein Diet ◽

M2 Macrophage ◽

Sprague Dawley ◽

Inkt Cells ◽

Low Protein ◽

Sprague Dawley Rats ◽

Male Neonate

Download Full-text

Body weight loss, effective satiation and absence of homeostatic neuropeptide compensation in male Sprague Dawley rats schedule fed a protein crosslinked diet

Appetite ◽

10.1016/j.appet.2017.06.029 ◽

2017 ◽

Vol 117 ◽

pp. 234-246 ◽

Cited By ~ 1

Author(s):

Nikki Cassie ◽

Richard L. Anderson ◽

Dana Wilson ◽

Anne Pawsey ◽

Julian G. Mercer ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Body Weight Loss ◽

Sprague Dawley ◽

Sprague Dawley Rats

Download Full-text

Prevention of stress-induced weight loss by third ventricle CRF receptor antagonist

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.5.r1461 ◽

1999 ◽

Vol 276 (5) ◽

pp. R1461-R1468 ◽

Cited By ~ 15

Author(s):

Gennady N. Smagin ◽

Leigh Anne Howell ◽

Stephen Redmann ◽

Donna H. Ryan ◽

Ruth B. S. Harris

Keyword(s):

Weight Loss ◽

Body Weight ◽

Receptor Antagonist ◽

Acute Stress ◽

Third Ventricle ◽

Corticotropin Releasing Factor ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Sustained Reduction ◽

Acute Responses

We previously reported that rats exposed to repeated restraint (3 h/day for 3 days) experience temporary hypophagia and a sustained reduction in body weight compared with nonrestrained controls. Studies described here determined the involvement of central corticotropin-releasing factor (CRF) receptors in the initiation of this chronic response to acute stress. In experiment 1, Sprague-Dawley rats were fitted with cannulas in the lateral ventricle and infused with 50 μg of αhCRF-(9—41) or saline immediately before restraint on each of the 3 days of restraint. The receptor antagonist inhibited hypophagia and weight loss on day 1 of restraint but not on days 2 and 3. In experiment 2, 10 μg of αhCRF-(9—41) or saline were infused into the third ventricle immediately before each restraint. The receptor antagonist totally blocked stress-induced hypophagia and weight loss. These results demonstrate that CRF receptors located in or near the hypothalamus mediate the acute responses to stress that lead to a permanent change in the hormonal or metabolic processes that determine body weight and body composition.

Download Full-text

Heat-stressed rat: effects of atropine, desalivation, or restraint

Journal of Applied Physiology ◽

10.1152/jappl.1982.53.5.1171 ◽

1982 ◽

Vol 53 (5) ◽

pp. 1171-1174 ◽

Cited By ~ 21

Author(s):

R. W. Hubbard ◽

C. B. Matthew ◽

R. Francesconi

Keyword(s):

Weight Loss ◽

Body Weight ◽

Exposure Time ◽

Heat Storage ◽

Physical Restraint ◽

Evaporative Cooling ◽

Heat Exposure ◽

Body Weight Loss ◽

Body Water ◽

Sprague Dawley

Heat-stressed rats thermoregulate behaviorally by spreading saliva onto body surfaces and thus lose body water through evaporative cooling. Prior to exploring the role of dehydration in our rat heatstroke model, we sought to compare the abilities of physical restraint, surgical desalivation, and/or atropine to increase the rate of body heat storage by inhibiting body water loss and evaporative cooling during heat exposure. In these experiments, male Sprague-Dawley rats were stressed at an ambient temperature of 41.5 degrees C either in their own cages or in a restraining device until a rectal temperature of 42.6 degrees C was attained. Unrestrained control rats heat-stressed at this temperature lost approximately 8% of body weight (water) during a 258-min exposure. Physical restraint or desalivation reduced both the exposure time and body weight loss by about 72%. Surgically desalivated, heat-stressed rats were observed to engage in voluntary urine-spreading behavior. Maximal heat storage and therefore maximal reduction in exposure time and inhibition of body weight loss to less than 10% of control values were achieved by either physical restraint plus desalivation or by a 500-micrograms dose of atropine.

Download Full-text

Energy balance and regulation of body weight after intestinal bypass surgery in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1983.245.5.r658 ◽

1983 ◽

Vol 245 (5) ◽

pp. R658-R663 ◽

Cited By ~ 1

Author(s):

R. L. Atkinson ◽

E. L. Brent ◽

B. S. Wagner ◽

J. H. Whipple

Keyword(s):

Weight Loss ◽

Body Weight ◽

Energy Balance ◽

Energy Expenditure ◽

Bypass Surgery ◽

Calorie Intake ◽

Intestinal Bypass ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Body Weights

This study evaluated the possibility that intestinal bypass surgery alters energy balance and regulation of body weight. In two sets of experiments, male Sprague-Dawley rats underwent bypass or sham bypass surgery. In experiment 1, half of each group was overfed and half was underfed. Bypass reduced net calorie intake (intake - fecal loss) at 2 wk but not at 6 wk. Body weights were maintained at a much lower level in the bypass rats, yet apparent energy expenditure was greater. In experiment 2, bypass rats were compared with sham bypass and sham bypass who were food restricted for paired-weight-loss to bypass (PWL sham). Net calorie intake and body weights of bypass and sham bypass followed a similar pattern as in experiment 1. At similar levels of body weight postoperatively, bypass rats required more calories per kilogram than did the PWL shams, suggesting that bypass resets downward the level at which body weight is regulated. Calorie requirements correlated with food intake better than with absolute body weight. Further studies to determine the mechanism of altered energy expenditure may provide methods for weight loss without extensive surgery.

Download Full-text

EXTH-74. IND-ENABLING CHARACTERIZATION OF DUAL DRD2- AND ClpP-TARGETING AGENT ONC206 AS THE NEXT IMIPRIDONE FOR CLINICAL NEURO-ONCOLOGY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.428 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii103-ii103

Author(s):

Varun Prabhu ◽

Sara Morrow ◽

Abed Rahman Kawakibi ◽

Yulia Jitkova ◽

Jinkyu Jung ◽

...

Keyword(s):

Body Weight ◽

Cell Lines ◽

Human Fibroblasts ◽

Xenograft Model ◽

Body Weight Loss ◽

Therapeutic Window ◽

Sprague Dawley ◽

Weight Changes ◽

Open Label ◽

Sprague Dawley Rats

Abstract ONC201 is the first bitopic antagonist of dopamine receptor D2 (DRD2) and allosteric mitochondrial protease ClpP agonist, that is well tolerated and induces durable tumor regressions in H3 K27M-mutant glioma patients. ONC206, a derivative of ONC201, is also a bitopic DRD2 antagonist that exhibits enhanced non-competitive effects, nanomolar potency, and disruption of DRD2 homodimers. In these studies, a FITC-casein degradation assay revealed that ONC206 also acts as an agonist of human ClpP and has a 3-fold improved potency. GEPIA database analysis showed ClpP mRNA was overexpressed in glioblastoma cells relative to normal cells. Broad nanomolar efficacy of ONC206 (GI50 < 78-889nM, 72h) was observed in >1,000 GDSC cancer cell lines with the highest sensitivity in cell lines exhibiting high ClpP and/or DRD2+/DRD5- RNA expression signatures. Among solid tumors, nervous system related cell lines were particularly sensitive. ONC206 reduced the viability of normal human fibroblasts at higher doses (GI50 > 5µM), suggesting a wide therapeutic window. Antitumor efficacy without body weight loss was observed with 50 mg/kg weekly oral ONC206 in a subcutaneous xenograft model of DRD2-overexpressing, dopamine-secreting tumor cells. Oral ONC206 at 50mg/kg exhibited a ~12 µM plasma Cmax and ~6 hours terminal half-life in Sprague-Dawley rats. Additionally, 5–10 fold higher ONC206 concentrations were observed in adrenal gland, bile duct, brain and bone marrow relative to plasma. GLP toxicology studies with weekly oral ONC206 in Sprague-Dawley rats and beagle dogs revealed no dose-limiting toxicities. Mild and reversible body weight changes were observed at the highest evaluated dose in both species. The no-observed-adverse-effect level was ≥ 16.7 mg/kg in dogs and ≥ 50 mg/kg in rats that exceed efficacious doses. A 50 mg starting dose of ONC206 was selected for the first-in-human open label, dose escalation, and food effect Phase I study in biomarker-enriched adult recurrent primary CNS tumors.

Download Full-text