scholarly journals Intranasal Leptin Reduces Appetite and Induces Weight Loss in Rats with Diet-Induced Obesity (DIO)

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 143-153 ◽  
Author(s):  
Carla Schulz ◽  
Kerstin Paulus ◽  
Olaf Jöhren ◽  
Hendrik Lehnert

Resistance to brain-mediated effects of leptin is a characteristic feature of obesity, resulting from alterations in leptin receptor signaling in hypothalamic neurons and/or transport across the blood-brain-barrier. We have shown previously, that the latter can be circumvented by intranasal (i.n.) application of leptin in lean rats. This prompted us to test i.n. leptin in animals with diet-induced obesity (DIO) as a basis for future human administration. DIO was induced in male Wistar rats by feeding a cafeteria diet for 25 or 32 wk, respectively. Consecutively, these DIO animals (seven to eight per treatment) and standard diet rats (lean) (14–15 per treatment, matched for age and diet duration) were treated with 0.1, 0.2 mg/kg leptin, or control solution i.n. daily for 4 wk before onset of dark period. Energy intake and body weight were measured daily; blood glucose, serum insulin, and leptin were measured before and after treatment. Expression of hypothalamic neuropeptides was assessed by quantitative real-time PCR. We demonstrate, for the first time, that i.n. leptin reduces appetite and induces weight loss in DIO to the same extent as in lean rats. Our findings are supported accordingly by an altered expression pattern of anorexigenic and orexigenic neuropeptides in the hypothalamus, e.g. proopiomelanocortin, cocaine and amphetamine-related transcript, neuropeptide Y, agouti-related protein. It now appears clear that i.n. leptin is effectively acting in obese animals in the same fashion as in their lean counterparts. These findings now clearly warrant studies in humans and may open new perspectives in the treatment of obesity.

2010 ◽  
Vol 163 (6) ◽  
pp. 895-900 ◽  
Author(s):  
N H Birkebæk ◽  
A Lange ◽  
P Holland-Fischer ◽  
K Kristensen ◽  
S Rittig ◽  
...  

ObjectiveObesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary–gonadal axis is rarely investigated. The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary–gonadal axis.MethodsOne hundred and sixteen (65 females) obese children with a median age of 12.3 (7–15) years were examined before and after a 10-week stay at a weight loss camp. Examination included anthropometry and fasting blood samples measuring plasma glucose, serum insulin, SHBG, DHEAS, testosterone, 17β-oestradiol, FSH and LH.ResultsBody mass index (BMI) decreased (P<0.01), insulin sensitivity and SHBG increased (P<0.01), independent of gender and puberty. The changes in insulin sensitivity and the changes in SHBG correlated significantly (P<0.01) independent of gender, puberty and the changes in BMI. Testosterone increased in boys (P<0.01) and tended to decrease in girls (P=0.05, in girls after menarche (P=0.03)). FSH increased in boys and girls. LH increased in boys and was unchanged in girls.ConclusionsDuring weight loss, insulin sensitivity and SHBG increased significantly in obese children, and the changes in insulin sensitivity and the changes in SHBG correlated significantly independent of gender, puberty and the changes in BMI. There was sexual dimorphism in the changes of testosterone, with the changes in boys towards increased virilisation and the changes in girls towards less virilisation.


2011 ◽  
Vol 301 (2) ◽  
pp. E274-E280 ◽  
Author(s):  
Koji Sato ◽  
Motoyuki Iemitsu ◽  
Katsuji Aizawa ◽  
Noboru Mesaki ◽  
Satoshi Fujita

This study was undertaken to assess the effects of dehydroepiandrosterone (DHEA) administration and exercise training on muscular DHEA and 5α-dihydrotestosterone (DHT) levels and hyperglycemia in diet-induced obese and hyperglycemic rats. After 14 wk of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of three 6-wk regimens: control, DHEA treatment, or exercise training (running at 25 m/min for 1 h, 5 days/wk; n = 10 each group). Results indicate that either 6 wk of DHEA treatment or exercise training significantly attenuated serum insulin and fasting glucose levels compared with the control group. Plasma and muscle concentrations of DHEA and DHT and expression levels of 5α-reductase were significantly higher in the DHEA-treated and exercise-training groups. Moreover, both DHEA administration and exercise training upregulated GLUT4 translocation with concomitant increases in protein kinase B and protein kinase Cζ/λ phosphorylation. Muscle DHEA and DHT concentrations closely correlated with blood glucose levels (DHEA treatment: r = −0.68, P < 0.001; exercise training: r = −0.65, P < 0.001), serum insulin levels, and activation of the GLUT4-regulated signaling pathway. Thus, increased levels of muscle sex steroids may contribute to improved fasting glucose levels via upregulation of GLUT4-regulated signaling in diet-induced obesity and hyperglycemia.


2019 ◽  
Vol 16 (3) ◽  
pp. 62-68
Author(s):  
Aleksandr E. Neimark ◽  
Shushanna A. Eganian ◽  
Maxim I. Galchenko

BACKGROUND: The relevance of the problem of obesity today is not in doubt. One of the most effective treatments today is bariatric surgery. At the same time, the effectiveness of the surgical method is not always predictable, as it is influenced by various factors, including the psychological state of the patient. AIM: To study the psychological characteristics of patients with obesity before and after surgical (bariatric) treatment and to establish the relationship with weight loss. MATERIALS AND METHOD: The study involved 32 patients with morbid obesity before and a year after laparoscopic longitudinal resection of the stomach with an initial body mass index of 45.36 (+54.90; -33.00). Questionnaire used: Symptom Check List-90-R (L.R. Derogatis). Statistical data processing was carried out using the statistical programming language R. RESULTS: The presence or increase in the level of phobic anxiety (a persistent reaction of fear to certain people, situations and places) and psychotism (isolation, interpersonal isolation, avoidance) in a patient can have a negative impact on the success of weight loss in the postoperative period. CONCLUSIONS. The psychological factors affecting the prognosis of weight loss after bariatric surgery have been identified. Psychological testing and determining the patients psychotype can be predictive in improving the outcome of surgical treatment of obesity.


Author(s):  
Alicia Huazano-García ◽  
Hakdong Shin ◽  
Mercedes G. López

Agavins consumption has lead to accelerate body weight loss in mice. We investigated the changes on cecal microbiota and short chain fatty acids (SCFA) associated to body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high fat (HF5) diet for 5 weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST+A10) or oligofructose (HF-ST+O10), five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t-test, P &lt; 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t-test, P &lt; 0.05). After diet shifted, HF-ST10 normalized its microbiota, increase its diversity and SCFA levels, whereas agavins (HF-ST+A10) or oligofructose (HF-ST+O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio as well as higher SCFA levels (P &lt; 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA &gt; 3.0); this enrichment has not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced extent of diversity and increased SCFA. Furthermore, identification of bacteria enriched by agavins, opens opportunities to explore new probiotics.


2014 ◽  
Vol 24 (5) ◽  
pp. 908-915 ◽  
Author(s):  
Shanhui Liang ◽  
Yuqi Zhou ◽  
Yiran Chen ◽  
Guihao Ke ◽  
Hao Wen ◽  
...  

ObjectiveThe aim of this study is to investigate whether EIF4A1, EIF4E, and EIF4G1 can serve as prognostic markers for patients with cervical cancer receiving preoperative brachytherapy.Materials and MethodsTissue microarrays composed of 35 normal cervix samples, 87 cervical cancers treated without preoperative therapy, and 50 pairs of cervical cancer tissues collected before and after preoperative brachytherapy were constructed and evaluated for the expression of EIF4A1, EIF4E, and EIF4G using immunohistochemistry. Immunohistochemical staining was scored by the staining intensity and the percentages of tumor cells. The χ2 test was used to analyze the association between the immunohistochemistry results and clinicopathologic variables. The Kaplan-Meier method was applied to analyze the disease-specific survival.ResultsOverexpression of EIF4A1, EIF4E, and EIF4G1 were detected in 83.9%, 84.7%, and 80.3% of cervical cancers, respectively, all of which were significantly related to advanced International Federation of Gynecology and Obstetrics stage, squamous cell histology, lymph node metastasis, and deep stromal invasion (P < 0.05). The altered expression pattern of EIF4A1 and EIF4E after preoperative brachytherapy was significantly correlated with the cervical cancer response to brachytherapy (P = 0.029 and 0.012, respectively). The decreased expression of EIF4A1 predicted better tumor-specific survival (P = 0.02). The alteration of EIF4A1 was an independent predictor for tumor-specific survival (P = 0.047; hazards ratio, 0.272; 95% confidence interval, 0.076–0.982).ConclusionsOverexpression of EIF4A1, EIF4E, and EIF4G1 were acquired malignant phenotypic features of cervical cancer. EIF4A1 might function as a novel prognostic indicator and a potential therapeutic target for cervical cancer.


2020 ◽  
Vol 20 (8) ◽  
pp. 1232-1243 ◽  
Author(s):  
Walter Milano ◽  
Valeria De Biasio ◽  
Walter Di Munzio ◽  
Giuseppina Foggia ◽  
Anna Capasso

Background: The increase in global obesity rates over the past three decades has been remarkable, a true epidemic, both in developed and in developing countries. The projections, based on current trends, suggest an increase in the prevalence of obesity at 60% in adult men, 40% in adult women and 25% in children in 2050. Given the limitations of lifestyle and surgery interventions bariatric, drug therapy approaches for the treatment of obesity, therefore become important options. Aim: The purpose of this review is a review of the literature, based on research on MEDLINE until 2019, on the possible pharmacological options in the treatment of obesity. Results: Currently, the FDA has approved several molecules for the treatment of obesity, both in monotherapy and in combination. Pharmacological monotherapies focus mainly on a single protein target and include orlistat, lorcaserin and liraglutide while the combination molecules propose a multitarget approach and include phentermine/topiramate and naltrexone/bupropion. All the approved drugs showed, in the different studies, a weight reduction of at least 5%, compared to placebo, in 52 weeks of observation. Phentermine-topiramate and liraglutide have been associated with the highest probability of at least 5% weight loss. Liraglutide and naltrexone-bupropion had the lowest rates of therapy discontinuation due to adverse events. Conclusion: The drugs, associated with the standard diet and/or exercise protocols, represent a good therapeutic opportunity to allow not only weight loss but also to reduce the risk of developing diseases caused by obesity, particularly cardiovascular diseases, and to maintain the set objectives over time. However, future research on the pharmacological treatment of obesity should encourage greater personalization of therapy, given the differences in safety, efficacy and response to therapy, in the different subpopulations of patients with obesity.


2005 ◽  
Vol 93 (S1) ◽  
pp. S157-S161 ◽  
Author(s):  
Nathalie M. Delzenne ◽  
Patrice D. Cani ◽  
Catherine Daubioul ◽  
Audrey M. Neyrinck

In the present paper, we summarise the data supporting the following hypothesis: dietary inulin-type fructans extracted from chicory root may modulate the production of peptides, such as incretins, by endocrine cells present in the intestinal mucosa, this phenomenon being involved in the regulation of food intake and/or systemic effects. To test this hypothesis, male Wistar rats received for 3 weeks either a standard diet or the same diet supplemented with 10% inulin-type fructans with different degrees of polymerisation. All the effects were most pronounced with the diet containing oligofructose, and consisted of (i) a decrease in mean daily energy intake and in epididymal fat mass; (ii) a higher caecal pool of the anorexigenic glucagon-like peptide-1 (7–36) amide (GLP-1), and peptide YY (PYY), due to caecal tissue proliferation; (iii) an increase in GLP-1 and of its precursor – proglucagon mRNA – concentrations in the proximal colon; (iv) an increase in portal serum level of GLP-1 and PYY; (v) a decrease in serum orexigenic peptide ghrelin. Moreover, oligofructose supplementation improved glucose homeostasis (i.e. decreased glycaemia, increased pancreatic and serum insulin content) in diabetic rats previously treated with streptozotocin, a phenomenon that is partly linked to the reduction in food intake and that correlates with the increase in colic and portal GLP-1 content. Based on these results it appears justified to test, in human subjects, the hypothesis that dietary inulin-type fructans could play a role in the management of obesity and diabetes through their capacity to promote secretion of endogenous gastrointestinal peptides involved in appetite regulation.


2011 ◽  
Vol 107 (7) ◽  
pp. 996-1005 ◽  
Author(s):  
Flávia Regina Gonçalves de Araújo ◽  
Célia Maria Machado Barbosa de Castro ◽  
Judith Advíncula Rocha ◽  
Bruno Sampaio ◽  
Maria de Fátima Alves Diniz ◽  
...  

The aim of the present study was to analyse the bacteriological factors during the process of dental alveolitis, relating it to a higher incidence of bacteraemia in adult rats subjected to neonatal malnutrition. We used forty male Wistar rats, suckled by mothers fed a diet during lactation containing 17 % protein in the nourished group (N) or 8 % protein in the undernourished group (UN). After weaning, the animals were given the Labina standard diet. After 90 d, these animals underwent upper right incisor extraction and induction of alveolitis. The oral microbiota was obtained using a swab and blood culture through venous blood. These procedures were performed before the extraction, 5 min after extraction, on the 21st day after alveolitis for groups N-21 and UN-21 and on the 28th day after alveolitis for groups N-28 and UN-28. Data were expressed as means and standard deviations for parametric data, and as medians and interquartile intervals for non-parametric data. Statistical significance was considered by assuming a critical level of 5 %. Before and after extraction, lower bacterial growth was observed per colony-forming unit (CFU) in the perialveolar region of the upper right incisors of undernourished animals, while the opposite was true after alveolitis, when a larger number of CFU was observed in these animals. The percentage of positive blood cultures obtained after alveolitis was greater in the undernourished animals. The present study thus demonstrated the influence of neonatal malnutrition in the perialveolar microbiota and in the development of bacteraemia after dental alveolitis.


Author(s):  
Alicia Huazano-García ◽  
Hakdong Shin ◽  
Mercedes G. López

Agavins consumption has lead to accelerate body weight loss in mice. We investigated the changes on cecal microbiota and short chain fatty acids (SCFA) associated to body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high fat (HF5) diet for 5 weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST+A10) or oligofructose (HF-ST+O10), five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t-test, P &lt; 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t-test, P &lt; 0.05). After diet shifted, HF-ST10 normalized its microbiota, increase its diversity and SCFA levels, whereas agavins (HF-ST+A10) or oligofructose (HF-ST+O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio as well as higher SCFA levels (P &lt; 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA &gt; 3.0), which have not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced extent of diversity and increased SCFA. Furthermore, identification of bacteria enriched by agavins, opens opportunities to explore new probiotics.


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