scholarly journals Phosphoinositide-Specific Inositol Polyphosphate 5-Phosphatase IV Inhibits Inositide Trisphosphate Accumulation in Hypothalamus and Regulates Food Intake and Body Weight

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5385-5399 ◽  
Author(s):  
Daniela F. Bertelli ◽  
Eliana P. Araújo ◽  
Maristela Cesquini ◽  
Graziela R. Stoppa ◽  
Miriam Gasparotto-Contessotto ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Body Weight Loss ◽  
Pi3 Kinase ◽  
Inositol Polyphosphate ◽  
Intracellular Signals ◽  
Antisense Approach ◽  
Inositol Phosphatases

The enzyme phosphatidylinositol 3-kinase (PI3-kinase) exerts an important role in the transduction of the anorexigenic and thermogenic signals delivered by insulin and leptin to first-order neurons of the arcuate nucleus in the hypothalamus. The termination of the intracellular signals generated by the activation of PI3-kinase depends on the coordinated activity of specific inositol phosphatases. Here we show that phosphoinositide-specific inositol polyphosphate 5-phosphatase IV (5ptase IV) is highly expressed in neurons of the arcuate and lateral nuclei of the hypothalamus. Upon intracerebroventricular (ICV) treatment with insulin, 5ptase IV undergoes a time-dependent tyrosine phosphorylation, which follows the same patterns of canonical insulin signaling through the insulin receptor, insulin receptor substrate-2, and PI3-kinase. To evaluate the participation of 5ptase IV in insulin action in hypothalamus, we used a phosphorthioate-modified antisense oligonucleotide specific for this enzyme. The treatment of rats with this oligonucleotide for 4 d reduced the hypothalamic expression of 5ptase IV by approximately 80%. This was accompanied by an approximately 70% reduction of insulin-induced tyrosine phosphorylation of 5ptase IV and an increase in basal accumulation of phosphorylated inositols in the hypothalamus. Finally, inhibition of hypothalamic 5ptase IV expression by the antisense approach resulted in reduced daily food intake and body weight loss. Thus, 5ptase IV is a powerful regulator of signaling through PI3-kinase in hypothalamus and may become an interesting target for therapeutics of obesity and related disorders.

Endurance exercise training increases insulin responsiveness in isolated adipocytes through IRS/PI3-kinase/Akt pathway

2005 ◽  
Vol 98 (3) ◽  
pp. 1037-1043 ◽  
Author(s):  
Sidney B. Peres ◽  
Solange M. Franzói de Moraes ◽  
Cecilia E. M. Costa ◽  
Luciana C. Brito ◽  
Julie Takada ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Exercise Training ◽  
Insulin Receptor ◽  
Endurance Exercise ◽  
Pi3 Kinase ◽  
Akt Pathway ◽  
Β Subunit ◽  
Endurance Exercise Training ◽  
Isolated Adipocytes

Endurance exercise training promotes important metabolic adaptations, and the adipose tissue is particularly affected. The aim of this study was to investigate how endurance exercise training modulates some aspects of insulin action in isolated adipocytes and in intact adipose tissue. Male Wistar rats were submitted to daily treadmill running (1 h/day) for 7 wk. Sedentary age-matched rats were used as controls. Final body weight, body weight gain, and epididymal fat pad weight did not show any statistical differences between groups. Adipocytes from trained rats were smaller than those from sedentary rats (205 ± 16.8 vs. 286 ± 26.4 pl; P < 0.05). Trained rats showed decreased plasma glucose (4.9 ± 0.13 vs. 5.3 ± 0.07 mM; P < 0.05) and insulin levels (0.24 ± 0.012 vs. 0.41 ± 0.049 mM; P < 0.05) and increased insulin-stimulated glucose uptake (23.1 ± 3.1 vs. 12.1 ± 2.9 pmol/cm2; P < 0.05) compared with sedentary rats. The number of insulin receptors and the insulin-induced tyrosine phosphorylation of insulin receptor-β subunit did not change between groups. Insulin-induced tyrosine phosphorylation insulin receptor substrates (IRS)-1 and -2 increased significantly (1.57- and 2.38-fold, respectively) in trained rats. Insulin-induced IRS-1/phosphatidylinositol 3 (PI3)-kinase (but not IRS-2/PI3-kinase) association and serine Akt phosphorylation also increased (2.06- and 3.15-fold, respectively) after training. The protein content of insulin receptor-β subunit, IRS-1 and -2, did not differ between groups. Taken together, these data support the hypothesis that the increased adipocyte responsiveness to insulin observed after endurance exercise training is modulated by IRS/PI3-kinase/Akt pathway.

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 Detoxification of a toxic variety of Jatropha curcas using heat and chemical treatments, and preliminary nutritional evaluation with rats

2003 ◽  
Vol 21 (1) ◽  
pp. 51 ◽  
Author(s):  
E. M. Aregheore ◽  
K. Becker ◽  
H.P.S. Makkar
Keyword(s):  
Growth Rate ◽  
Body Weight ◽  
Food Intake ◽  
Jatropha Curcas ◽  
Nutritive Value ◽  
Body Weight Loss ◽  
Casein Diet ◽  
Sprague Dawley ◽  
Chemical Treatments ◽  
Diet Control

Seeds from a toxic variety of Jatropha curcas (Capo Verde, Nicaragua) were processed, defatted and ground to obtain the meal. The meal was subjected to heat and 14 different chemical treatments to detoxify the meal of lectin and phorbolesters. Heat treatment inactivated lectin, but not phorbolester. One of the treatments reduced phorbolesters to a tolerable level of 0.09 mg/g. The treated meals with other ingredients were used in diets to assess acceptance and nutritive value of detoxified Jatropha curcas meal in two experiments. Experiments 1 and 2 had twelve (12) male weanling rats each, Sprague Dawley strain, 28-30 days old, pre-experimental average body weights of 8379±7.2 and 84.6±6.4 g, respectively. They were divided into three groups according to body weight and fed casein diet (control) and two diets in which Jatropha curcas was the protein source. In experiment 1, the rats accepted diet 1, but did not fully accept diet 2. Food intake, growth rate, protein efficiency ratio (PER) and food transformation index (T1) were significantly better (P<0.05) in diet 1 than in the casein and diet 2. In experiment 2, casein diet was better (P<0.05) in food intake, growth rate, PER and TI than diets 1 and 2. Food intake with Jatropha meal was significantly reduced and the rats had drastic body weight loss (P<0.05) and this might be due to the presence of phorbolesters in the diets. Generally, the presence of phorbolesters in food has significant effect on its acceptance. Jatropha meal obtained from treatment 3 had a crude protein (CP) content of 68%, far higher than the CP content of most oilseed meals (soyabean). This treatment seems a better method of detoxifying Jatropha curcas meal for livestock but in economic terms it is expensive to produce a meal from it.

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 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 &lt; 0.05) and body weight-lowering (P &lt; 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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