Reduced feeding response to neuropeptide Y in senescent Fischer 344 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.

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

American Journal of Clinical Nutrition ◽

10.1093/ajcn/35.2.284 ◽

1982 ◽

Vol 35 (2) ◽

pp. 284-293 ◽

Cited By ~ 65

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

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

Obesity Surgery ◽

10.1007/s11695-007-9392-8 ◽

2008 ◽

Vol 18 (4) ◽

pp. 415-422 ◽

Cited By ~ 25

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

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

Frontiers in Pharmacology ◽

10.3389/fphar.2020.594706 ◽

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.

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

Endocrinology ◽

10.1210/en.2008-0770 ◽

2008 ◽

Vol 149 (11) ◽

pp. 5679-5687 ◽

Cited By ~ 102

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.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00147.2013 ◽

2014 ◽

Vol 306 (1) ◽

pp. R34-R44 ◽

Cited By ~ 7

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.

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

Drug Research ◽

10.1055/a-1201-2700 ◽

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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Anorectic Effects of the Cytokine, Ciliary Neurotropic Factor, Are Mediated by Hypothalamic Neuropeptide Y: Comparison with Leptin*

Endocrinology ◽

10.1210/endo.139.2.5723 ◽

1998 ◽

Vol 139 (2) ◽

pp. 466-473 ◽

Cited By ~ 51

Author(s):

B. Xu ◽

M. G. Dube ◽

P. S. Kalra ◽

W. G. Farmerie ◽

A. Kaibara ◽

...

Keyword(s):

Gene Expression ◽

Weight Loss ◽

Body Weight ◽

Food Intake ◽

Neuropeptide Y ◽

Messenger Rna ◽

Nervous System Development ◽

Ribonuclease Protection Assay ◽

Dependent Manner ◽

Neurotropic Factor

Abstract Although ciliary neurotropic factor (CNTF) is a tropic factor in nervous system development and maintenance, peripheral administration of this cytokine also causes severe anorexia and weight loss. The neural mechanism(s) mediating the loss of appetite is not known. As hypothalamic neuropeptide Y (NPY) is a potent orexigenic signal, we tested the hypothesis that CNTF may adversely affect NPYergic signaling in the hypothalamus. Intraperitoneal administration of CNTF (250μ g/kg) daily for 4 days significantly suppressed 24-h food intake in a time-dependent manner and decreased body weight. The loss in body weight was similar to that which occurred in pair-fed (PF) rats. As expected, hypothalamic NPY gene expression, determined by measurement of steady state prepro-NPY messenger RNA by ribonuclease protection assay, significantly increased in PF rats in response to energy imbalance. However, despite a similar loss in body weight, there was no increase in NPY gene expression in CNTF-treated rats. Daily administration of CNTF intracerebroventricularly (0.5 or 5.0 μg/rat) also produced anorexia and body weight loss. In this experiment, negative energy balance produced by both PF and food deprivation augmented hypothalamic NPY gene expression. However, despite reduced intake and loss of body weight, no similar increment in hypothalamic NPY gene expression was observed in CNTF-treated rats. In fact, in rats treated with higher doses of CNTF (5.0 μg/rat), NPY gene expression was reduced below the levels seen in control, freely fed rats. Furthermore, CNTF treatment also markedly decreased NPY-induced feeding. These results suggested that anorexia in CNTF-treated rats may be due to a deficit in NPY supply and possibly in the release and suppression of NPY-induced feeding. The possibility that CNTF-induced anorexia may be caused by increased leptin was next examined. Daily intracerebroventricular injections of leptin (7 μg/rat) decreased food intake, body weight, and hypothalamic NPY gene expression in a manner similar to that seen after CNTF treatment. Leptin administration also suppressed NPY-induced feeding. However, peripheral and central CNTF injections markedly decreased leptin messenger RNA in lipocytes, indicating a deficiency of leptin in these rats; thus, leptin was unlikely to be involved in appetite suppression. Thus, these results show that a two-pronged central action of CNTF, causing diminution in both NPY availability and the NPY-induced feeding response, may underlie the severe anorexia. Further, unlike other members of the cytokine family, suppression of NPYergic signaling in the hypothalamus by CNTF does not involve up-regulation of leptin, but may involve a direct action on hypothalamic NPY neurons or on neural circuits that regulate NPY signaling in the hypothalamus.

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