Olanzapine Administration Reduces Chemotherapy-Induced Nausea Behavior in Rats

2021 ◽  
pp. 109980042110004
Author(s):  
Rosario B. Jaime-Lara ◽  
Tito Borner ◽  
Ruby A. Holland ◽  
Evan Shaulson ◽  
Brianna Brooks ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Side Effects ◽  
Energy Balance ◽  
Food Intake ◽  
Body Weight Loss ◽  
Brain Regions ◽  
Nausea And Vomiting ◽  
Behavioral Experiments ◽  
Mrna Expression Levels

Nausea and vomiting are consistently identified among the most distressing side effects of chemotherapy. In recent years, Olanzapine (OLZ) treatment was added to anti-emetic guidelines as a treatment for chemotherapy-induced nausea and vomiting (CINV), despite little available data supporting a mechanism behind the positive benefits of the drug. Here, we examine whether OLZ reduces cisplatin chemotherapy-induced side effects on food intake and pica behavior in rats (i.e., kaolin intake, a proxy for nausea/emesis). Behavioral experiments tested whether systemic or hindbrain administration of OLZ ameliorated cisplatin-induced pica, anorexia, and body weight loss in rats. We also tested whether systemic OLZ reduces cisplatin-induced neuronal activation in the dorsal vagal complex (DVC), a hindbrain region controlling emesis. Lastly, given their role in regulating feeding and emesis, circulating ghrelin levels and central mRNA expression levels of serotonin (HT) receptor subunits, including 5-HT2C, were measured in brain regions that regulate CINV and energy balance in an exploratory analysis to investigate potential mediators of OLZ action. Our results show that both systemic and hindbrain administration of OLZ attenuated cisplatin-induced kaolin intake and body weight loss, but not anorexia. Systemic OLZ decreased cisplatin-induced c-Fos immunofluorescence in the DVC and prevented cisplatin-induced reductions in circulating ghrelin levels. IP OLZ also blocked cisplatin-induced increases in Htr2c expression in DVC and hypothalamic micropunches. These data suggest hindbrain exposure to OLZ is sufficient to induce reductions in cisplatin-induced pica and that central serotonergic signaling, via 5-HT2C, and changes in circulating ghrelin may be potential mediators of olanzapine anti-emetic action.

The effects of ileal transposition on food intake and body weight loss in VMH-obese rats

1982 ◽  
Vol 35 (2) ◽  
pp. 284-293 ◽  
Author(s):  
H S Koopmans ◽  
A Sclafani ◽  
C Fichtner ◽  
P F Aravich
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Body Weight Loss ◽  
Ileal Transposition ◽  
Obese Rats

Gastric Bypass Surgery Causes Body Weight Loss Without Reducing Food Intake in Rats

2008 ◽  
Vol 18 (4) ◽  
pp. 415-422 ◽  
Author(s):  
Marianne W. Furnes ◽  
Karin Tømmerås ◽  
Carl-Jørgen Arum ◽  
Chun-Mei Zhao ◽  
Duan Chen
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Body Weight ◽  
Food Intake ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Body Weight Loss

scholarly journals Therapeutic Effects of Licorice and Dried Ginger Decoction on Activity-Based Anorexia in BALB/c AnNCrl Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Do-Hyun Kim ◽  
Joong Sun Kim ◽  
Jeongsang Kim ◽  
Jong-Kil Jeong ◽  
Hong-Seok Son ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Body Weight Loss ◽  
Drop Out ◽  
Therapeutic Effects ◽  
Excessive Sweating ◽  
Dopamine Concentration ◽  
Wheel Activity ◽  
The Brain

Licorice and dried ginger decoction (Gancao-ganjiang-tang, LGD) is used for nausea and anorexia, accompanied by excessive sweating in Traditional Chinese Medicine. Herein, we investigated the therapeutic effects of LGD using the activity-based anorexia (ABA) in a mouse model. Six-week-old female BALB/c AnNCrl mice were orally administered LGD, water, licorice decoction, dried ginger decoction, or chronic olanzapine, and their survival, body weight, food intake, and wheel activity were compared in ABA. Additionally, dopamine concentration in brain tissues was evaluated. LGD significantly reduced the number of ABA mice reaching the drop-out criterion of fatal body weight loss. However, LGD showed no significant effects on food intake and wheel activity. We found that in the LGD group the rise of the light phase activity rate inhibited body weight loss. Licorice or dried ginger alone did not improve survival rates, they only showed longer survival periods than chronic olanzapine when combined. In addition, LGD increased the dopamine concentration in the brain. The results from the present study showed that LGD improves the survival of ABA mice and its mechanism of action might be related to the alteration of dopamine concentration in the brain.

scholarly journals Diet-related Behaviors Are Associated with Energy Intake and Body Weight Loss During a Sustained Military Training Exercise (P16-012-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Heather Fagnant ◽  
Tracey Smith ◽  
Susan McGraw ◽  
Julie Smith ◽  
John Ramsay ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Energy Balance ◽  
Energy Intake ◽  
Diet Quality ◽  
Eating Behaviors ◽  
Military Training ◽  
Body Weight Loss ◽  
Nutrition Knowledge ◽  
Military Operations

Abstract Objectives Sustained negative energy balance during military operations contributes to degradations in physical and cognitive performance. Characterizing the diet-related behaviors and nutrition knowledge of Soldiers who self-select higher energy intakes during military operations may identify strategies for promoting energy balance. This study aimed to identify diet-related behaviors of Soldiers who self-selected higher energy intakes during a simulated military operation. Methods Dietary intake and body weight were measured daily in 54 Soldiers (91% male, BMI 25 ± 4 kg/m2, 25 ± 4 yr) participating in a 3-d military exercise. During the exercise, Soldiers were provided with military rations (2787–3003 kcal/d), and in some cases consumed items from home or mobile catering. Food frequency and nutrition knowledge questionnaires were completed before the exercise to assess diet quality by HEI-2010 total score and nutrition knowledge, respectively, and questionnaires assessing eating behaviors during the exercise were completed daily and after the exercise. Associations between diet quality, nutrition knowledge, and diet-related behaviors with 1) daily energy intake (EI) and 2) weight loss (∆BW) were determined by backwards elimination multiple linear regression. Results EI (mean ± SD: 1947 ± 627 kcal/d) and ∆BW (−1.4 ± 1.2%) during the exercise were not correlated. After adjusting for baseline BMI, EI was associated with diet quality (β ± SE: 17 ±9 kcal/d, P = 0.07) and eating frequency (170 ± 86 kcal/d, P = 0.06) and more often intentionally eating foods to improve performance (−389 ± 207 kcal/d, P = 0.07) during the exercise (R2 = 0.27, P = 0.03). In contrast, greater ∆BW was associated only with more often “not allowing myself to eat” certain foods during the exercise (R2 = 0.11; −0.8 ± 0.4%, P = 0.04). Nutrition knowledge was not a significant predictor in either model. Conclusions Findings suggest that self-selected energy intake and body weight loss during military operations may be associated with habitual adherence to healthier dietary patterns and conscious decisions regarding what and how often to eat and/or drink during operations, but not with general nutrition knowledge. Funding Sources U.S. Army Medical Research & Materiel Command; US Army Natick Research, Development, & Engineering Center. Disclaimer: Authors’ views do not reflect official DoD policy.

scholarly journals Cooperative interaction between leptin and amylin signaling in the ventral tegmental area for the control of food intake

2015 ◽  
Vol 308 (12) ◽  
pp. E1116-E1122 ◽  
Author(s):  
Elizabeth G. Mietlicki-Baase ◽  
Diana R. Olivos ◽  
Brianne A. Jeffrey ◽  
Matthew R. Hayes
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Ventral Tegmental Area ◽  
Balance Control ◽  
Body Weight Gain ◽  
Body Weight Loss ◽  
Cooperative Interaction ◽  
Cooperative Effects ◽  
Ventral Tegmental

Peripheral coadministration of amylin and leptin produces enhanced suppression of food intake and body weight, but the central nuclei mediating these effects remain unclear. Because each of these peptides controls feeding via actions at the ventral tegmental area (VTA), we tested the hypothesis that the VTA is a site of action for the cooperative effects of leptin and amylin on energy balance control. First, we show that intra-VTA injection of amylin and leptin at doses of each peptide that are effective in reducing food intake and body weight when administered separately produces an enhanced suppression of feeding when administered in combination. We also demonstrate that subthreshold doses of both amylin and leptin cause significant hypophagia and body weight loss when coadministered into the VTA. Additionally, we provide evidence that VTA amylin receptor blockade significantly attenuates the ability of intra-VTA leptin to reduce feeding and body weight gain. Together, these data provide the first evidence that the VTA mediates the interaction of amylin and leptin to cooperatively promote negative energy balance.

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.

High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus

2014 ◽  
Vol 306 (1) ◽  
pp. R34-R44 ◽  
Author(s):  
Beatriz de Carvalho Borges ◽  
Rodrigo Rorato ◽  
Ernane Torres Uchoa ◽  
Paula Marangon ◽  
Glauber S. F. da Silva ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Brain Stem ◽  
High Fat Diet ◽  
Control Diet ◽  
Body Weight Loss ◽  
Hypothalamic Nucleus ◽  
High Fat

Hypophagia induced by inflammation is associated with Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT) 3 signaling pathway, and leptin-mediated hypophagia is also mediated by JAK2-STAT3 pathway. We have previously reported that lipopolysaccharide (LPS) did not reduce food intake in leptin-resistant high-fat diet (HFD) rats but maintained body weight loss. We investigated whether changes in p-STAT3 expression in the hypothalamus and brain stem could account for the desensitization of hypophagia in HFD animals after a low LPS dose (100 μg/kg). Wistar rats fed standard diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 wk were assigned into control diet-saline, control diet-LPS, HFD-saline, and HFD-LPS groups. LPS reduced feeding in the control diet but not HFD. This group showed no p-STAT3 expression in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH), but sustained, though lower than control, p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus (RPa). LPS decreased body weight in HFD rats and increased Fos expression in the NTS. LPS increased body temperature, oxygen consumption, and energy expenditure in both control diet and HFD rats, and this response was more pronounced in HFD-LPS group. Brown adipose tissue (BAT) thermogenesis and increased energy expenditure seem to contribute to body weight loss in HFD-LPS. This response might be related with increased brain stem activation. In conclusion, LPS activates STAT3-mediated pathway in the hypothalamus and brain stem, leading to hypophagia, however, LPS effects on food intake, but not body weight loss, are abolished by leptin resistance induced by HFD. The preserved STAT3 phosphorylation in the brain stem suggests that unresponsiveness to LPS on STAT3 activation under HFD might be selective to the hypothalamus.

Reduced feeding response to neuropeptide Y in senescent Fischer 344 rats

2001 ◽  
Vol 280 (4) ◽  
pp. R1052-R1060 ◽  
Author(s):  
Cynthia A. Blanton ◽  
Barbara A. Horwitz ◽  
James E. Blevins ◽  
Jock S. Hamilton ◽  
Eduardo J. Hernandez ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Body Weight Loss ◽  
Fischer 344 Rats ◽  
Feeding Response ◽  
Fischer 344 ◽  
Progressive Weight Loss ◽  
Old Rats

The anorexia of aging syndrome in humans is characterized by spontaneous body weight loss reflecting diminished food intake. We reported previously that old rats undergoing a similar phenomenon of progressive weight loss (i.e., senescent rats) also display altered feeding behavior, including reduced meal size and duration. Here, we tested the hypothesis that blunted responsiveness to neuropeptide Y (NPY), a feeding stimulant, occurs concurrently with senescence-associated anorexia/hypophagia. Young (8 mo old, n = 9) and old (24–30 mo old, n = 11) male Fischer 344 rats received intracerebroventricular NPY or artificial cerbrospinal fluid injections. In response to a maximum effective NPY dose (10 μg), the net increase in size of the first meal after injection was similar in old weight-stable (presenescent) and young rats (10.85 ± 1.73 and 12.63 ± 2.52 g/kg body wt0.67, respectively). In contrast, senescent rats that had spontaneously lost ∼10% of body weight had significantly lower net increases at their first post-NPY meal (1.33 ± 0.33 g/kg body wt0.67) than before they began losing weight. Thus altered feeding responses to NPY occur in aging rats concomitantly with spontaneous decrements in food intake and body weight near the end of life.

Combination of Lorcaserin and GLP-1/glucagon Coagonist Improves Metabolic Dysfunction in Diet Induced-obese Mice

Drug Research ◽  
2020 ◽  
Vol 70 (08) ◽  
pp. 376-384
Author(s):  
Vishal Patel ◽  
Amit Joharapurkar ◽  
Samadhan Kshirsagar ◽  
Maulik Patel ◽  
Hardikkumar Savsani ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Body Weight Loss ◽  
Tolerance Test ◽  
Individual Therapy ◽  
Repeated Treatment ◽  
Obesity And Diabetes ◽  
Glucagon Receptors

Abstract Background Obesity and diabetes are major metabolic disorders that progress to severe morbidity and mortality. Neuroendocrine mechanisms controlling energy balance indicate that combination therapies are needed to sustain weight loss. Lorcaserin was one of the approved therapies for the treatment of obesity, which is recently withdrawn because a safety clinical trial, shows an increased occurrence of cancer. Coagonist of glucagon-like-peptide-1 (GLP-1) and glucagon receptors is a novel investigational therapy demonstrated to have both anti-obesity and anti-diabetic effect. Here, we investigated the effect of combination of lorcaserin and a GLP-1 and glucagon receptors coagonist in diet-induced obese (DIO) mice model. Methods The diet-induced obese C57BL/6J mice were used to assess acute and chronic effect of lorcaserin, coagonist of GLP-1and glucagon receptors and their combination on food intake, body weight, and biochemical parameters. Results In acute study, combination of lorcaserin and coagonist causes synergistic reductions in food intake and body weight. Repeated treatment of combination of lorcaserin and coagonist showed enhanced body weight loss over time, which is due to reduction in fat mass (subcutaneous, retroperitoneal, mesenteric and epididymal fat pad) compared to individual therapy. Also, suppression of locomotor activity seen with lorcaserin was not evident in combination with coagonist. No additive effect was observed in glucose tolerance (intraperitoneal glucose tolerance test or insulin tolerance test), serum lipids, hepatic lipids, and energy expenditure in combination group. Conclusion These data suggest that combination of lorcaserin and coagonist could be a better combination to induce body weight loss.

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