scholarly journals Serotonin as a Regulator of Leptin-Mediated Food Intake Control Within a Novel Neuronal Circuit Between the Hypothalamus and Raphe Nuclei

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A55-A56
Author(s):  
Alia T Sadek ◽  
Hanson B Cowan ◽  
Katie M Jimenez ◽  
Jesseca N Crawford ◽  
Nicholas D Maxwell ◽  
...  

Abstract The onset and exacerbation of obesity involves the overproduction of the adipocyte-derived hormone leptin, a key mediator of homeostatic appetite regulation and a signal for satiety. Although leptin’s hypothalamic regulation of food intake has been extensively investigated, its role in tandem with the anorectic neurotransmitter serotonin (5-HT) has been less characterized. 5-HT is synthesized in the dorsal raphe nucleus (DRN) where anatomical projections to many hypothalamic nuclei have previously been identified. Preliminary studies in our lab have: (1) identified serotonergic neurons responsive to leptin in the DRN that project to the arcuate nucleus (ARC) of the hypothalamus and (2) demonstrated leptin injected into the DRN significantly decreases food intake. The objective of the current study was to identify the role of 5-HT in leptin’s regulation of food intake first within the DRN, then between the DRN and the ARC. Adult male Sprague Dawley rats underwent stereotaxic surgery for guide cannula implantation in the DRN. After recovery, animals were administered 100 µg of p-chlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis, in the DRN each day for four days. On the fourth day, leptin was also administered in the DRN (5 µg/rat) and food intake was measured over a 24-hour time course. ANOVA analysis revealed a significant difference in 24-hour food intake [F (3, 18) = 3.972; P = 0.0246] and post-hoc analysis showed that animals treated with leptin significantly decreased food intake (17.2 ± 2.0 g) compared to control rats (25.4 ± 0.9 g), whereas PCPA-treated rats did not differ from the control rats, suggesting that depletion of 5-HT attenuated leptin’s ability to regulate food intake within the DRN. To examine the role of 5-HT on leptin’s hypothalamic action, a subsequent experiment was conducted by implanting an additional cannula into the ARC for the administration of leptin or vehicle on the fourth day of treatment. ANOVA analysis revealed a significant difference in 24-hour food intake [F (3, 16) = 5.998; P = 0.0061] and post-hoc analysis showed that only rats treated with leptin in the ARC significantly decreased food intake (14.0 ± 1.5 g) compared to controls (21.8 ± 0.5 g). 5-HT depletion was assessed post-mortem using immunohistochemistry and was later quantified. Collectively, these results demonstrate that leptin’s ability to regulate food intake is dependent on 5-HT, regardless of the area of regulation (i.e. DRN or the hypothalamus).

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1806
Author(s):  
Virginia Chan ◽  
Alyse Davies ◽  
Lyndal Wellard-Cole ◽  
Silvia Lu ◽  
Hoi Ng ◽  
...  

Technology-enhanced methods of dietary assessment may still face common limitations of self-report. This study aimed to assess foods and beverages omitted when both a 24 h recall and a smartphone app were used to assess dietary intake compared with camera images. For three consecutive days, young adults (18–30 years) wore an Autographer camera that took point-of-view images every 30 seconds. Over the same period, participants reported their diet in the app and completed daily 24 h recalls. Camera images were reviewed for food and beverages, then matched to the items reported in the 24 h recall and app. ANOVA (with post hoc analysis using Tukey Honest Significant Difference) and paired t-test were conducted. Discretionary snacks were frequently omitted by both methods (p < 0.001). Water was omitted more frequently in the app than in the camera images (p < 0.001) and 24 h recall (p < 0.001). Dairy and alternatives (p = 0.001), sugar-based products (p = 0.007), savoury sauces and condiments (p < 0.001), fats and oils (p < 0.001) and alcohol (p = 0.002) were more frequently omitted in the app than in the 24 h recall. The use of traditional self-report methods of assessing diet remains problematic even with the addition of technology and finding new objective methods that are not intrusive and are of low burden to participants remains a challenge.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suvanjaa Sivalingam ◽  
Emil List Larsen ◽  
Daniel H. van Raalte ◽  
Marcel H. A. Muskiet ◽  
Mark M. Smits ◽  
...  

AbstractGlucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.


2021 ◽  
Vol 6 (1) ◽  
pp. e000648
Author(s):  
Swetha Bindu Velaga ◽  
Muneeswar Gupta Nittala ◽  
Michael S Ip ◽  
Luc Duchateau ◽  
SriniVas R Sadda

Background/aimsOASIS is a Phase IIIb trial (NCT01429441) assessing long-term outcomes in subjects with symptomatic vitreomacular adhesion (VMA). The purpose of this study is to report on the frequency, severity, location and time course of ellipsoid zone (EZ) alterations in ocriplasmin-treated and sham control eyes in the OASIS study.Methods220 patients (146 ocriplasmin, 74 sham) subjects with VMA were enrolled in this masked post hoc analysis phase IIIb, randomised, sham-controlled double-masked multicentre clinical trial. A masked post hoc analysis of OCT images was performed at the Doheny Image Reading Center from subjects enrolled in the OASIS trial. The status of the EZ band was assessed in three different macular regions: the central subfield (CS) (≤1 mm diameter), the parafoveal area (PAA) (>1 to ≤3 mm) and the perifoveal area (PEA) (>3 to ≤6 mm). The EZ band was rated as normal/intact, full thickness macular hole (FTMH), abnormal but continuous, discontinuous/disrupted or absent at visits from baseline (pretreatment) to week 1 (day 7), month 1 (day 28), month 3, month 6, month 12 and the final follow-up at month 24. EZ band status was compared in both study and control eyes.ResultsA total of 208 patients (138 ocriplasmin, 70 sham) were included in this analysis. At baseline, FTMH was present in 48.6%, 8.0%, 0% and 52.8%, 2.9%, 0% in the CS, PAA and PEA of the ocriplasmin and sham groups, respectively. The EZ was graded to be abnormal but continuous, discontinuous/disrupted or absent at Baseline in 21.0%, 4.3%, 2.8% in the CS, PAA and PEA, respectively, of the ocriplasmin group; and 12.9%, 10.0%, 4.3% in the CS, PAA and PEA of the sham group. For the ocriplasmin group in the PAA, this frequency increased to 6.6% at week 1, was 9.8% at month 1, but improved to 3.8% at month 3, and remained stable to 1.6% at month 24. These differences, however, were not statistically significant.ConclusionsOcriplasmin treatment for symptomatic VMA was associated with EZ abnormalities in a small percentage of patients that was best assessed in regions (PEA) relatively unaffected by the VM interface disease at baseline. The EZ abnormalities were apparent by week 1, persisted at month 1, and appeared to resolve in the majority of cases by month 3.Trial registration numberNCT01429441


2016 ◽  
Vol 25 (2) ◽  
pp. 93-7 ◽  
Author(s):  
I B Rangga Wibhuti ◽  
Amiliana M. Soesanto ◽  
Fahmi Shahab

Background: Prior studies have compared the E/e’ elevation in preeclampsia patients to normal patients, however there are no data whether this elevation persists after birth. The aim of this study is to analyze diastolic function in preeclampsia patients during pre- and post-partum period using E/e’ parameter measurement.Methods: This is a prospective cohort study of pregnant women with preeclampsia who were hospitalized and planned for pregnancy termination. Basic clinical characteristics were obtained from all samples. Echocardiography was done prepartum, 48-72 hours after termination, and 40-60 days postpartum. Post hoc analysis using least significant difference method was used to compare the results between measurements.Results: 30 subjects were enrolled in the study. Analysis on E/e’ characteristics showed statistical difference between prepartum E/e’ and 40 days postpartum E/e’ (11.87±3.184 vs 9.43±2.529, p=0.001, CI=1.123-3.751), as well as between 48 hours post-partum and 40 days post-partum period (12.12±2.754 vs 9.43±2.529, p<0.001, CI=1.615-3.771). There were no statistical differences between pre-partum E/e’ and 48 hours post-partum E/e’ (11.87±3.184 vs 12.12±2.754, p=0.633, CI=-1.345-0.832).Conclusion: This study showed diastolic dysfunction in preeclampsia patients persists up until a few days after birth, but resolves in time (40 days after birth) as measured by tissue doppler imaging.


2020 ◽  
pp. 00711-2020
Author(s):  
W. R. Good ◽  
J. Garrett ◽  
H.-U. P. Hockey ◽  
L. Jayaram ◽  
C. Wong ◽  
...  
Keyword(s):  

2021 ◽  
Vol 32 ◽  
pp. S1125-S1126
Author(s):  
R.W. Hamacher ◽  
X. Liu ◽  
M.K. Schuler ◽  
L. Hentschel ◽  
P. Schöffski ◽  
...  

2014 ◽  
Vol 52 (3) ◽  
pp. 369-378
Author(s):  
Milan Ivkov ◽  
Ivana Blešić ◽  
Vidoje Stefanović ◽  
Jovanka Popov Raljić

Abstract The present paper studies managers’ perception of factors that influence customer satisfaction in the restaurant industry and their attitudes towards conducting a research on customer needs. In particular, we studied the managers’ perception of the importance of restaurant experience elements of customer satisfaction. The research involved 50 restaurant managers in Serbia. Through descriptive and ANOVA analysis, we differentiated two main profiles of restaurant managers in terms of age and professional education. Also, we found through LSD Post hoc test statistically significant difference among managers in regards to customers’ needs data collection. Restaurant managers need to obtain education in the hospitality industry and to pay more attention to customer needs in order to provide quality service.


1986 ◽  
Vol 64 (6) ◽  
pp. 683-688 ◽  
Author(s):  
Bernard Candas ◽  
Josée Lalonde ◽  
Maurice Normand

To develop a mathematical model of the distribution and metabolism of rat corticotropin-releasing factor (rCRF), the time course of 125I-labelled rCRF in plasma was measured in male Sprague–Dawley rats (i) following a rapid injection of 24 ng rCRF/100 g body weight (BW), or (ii) following a rapid injection of 424 ng rCRF/100 g BW, or (iii) during an infusion at a rate ranging from 0.28 to0.73 ng rCRF∙min−1∙100 g BW−1. The comparison of the one-, two-, and three-compartment models shows that the two-pool structure fits better to the dynamics of CRF in plasma as measured in each rat. Following a rapid injection the decay curve occurs in a biphasic manner; the early phase of disappearance is 25 times faster than the late one. There is no significant difference between the estimates of the metabolic clearance rate following both amplitudes of injection (0.40 ± 0.06 and 0.48 ± 0.05 mL∙min−1∙100 g BW−1). The volume of the first pool, 16.8 ± 1.1 mL/100 g BW, is four times larger than the plasma volume. It would thus appear that CRF is rapidly distributed from plasma into several tissues which are represented in the first pool of the model. The mean residence time of every CRF molecule in the second compartment, from the moment of secretion to its elimination, is from three to four times longer than in the first one. It stays, on average, between 140 min and 3 h in the system before an irreversible exit. At steady state, the disposal rate represents only 3% of the CRF mass of the first compartment every minute. These results could explain the prolonged effects of CRF on pituitary-adrenocortical secretion.


2020 ◽  
Vol 22 (12) ◽  
pp. 1176-1183
Author(s):  
Marco Fantinati ◽  
Julien Trnka ◽  
Amélia Signor ◽  
Séverine Dumond ◽  
Géraldine Jourdan ◽  
...  

Objectives The aim of the study was to evaluate the appetite-stimulating effect of gabapentin by comparing it with mirtazapine in healthy cats in the first 8 h after ovariectomy surgery. Methods This double-masked, placebo-controlled, prospective clinical trial included 60 healthy cats presented to the hospital for ovariectomy: 20 received gabapentin, 21 received mirtazapine and 19 received a placebo immediately before and 6 h after surgery. Food was offered at 2, 4, 6 and 8 h post-ovariectomy. After each meal, food intake was measured. Data were analysed using repeated-measure ANOVA and a linear mixed-model analysis. Post-hoc Tukey’s honest significant difference test was performed for multiple comparisons. Results Food intake increased in both treatment groups vs placebo. No statistically significant difference was found between cats treated with gabapentin or mirtazapine. Conclusions and relevance Cats receiving gabapentin ate more than cats in the placebo group. Thirty percent of cats in the gabapentin group covered their resting energy requirements, while none of the cats in the placebo group did. Gabapentin and mirtazapine produced similar effects on food intake.


2019 ◽  
Vol 33 (05) ◽  
pp. 481-485 ◽  
Author(s):  
Anthony V. Christiano ◽  
Christian A. Pean ◽  
David N. Kugelman ◽  
Sanjit R. Konda ◽  
Kenneth A. Egol

AbstractThe purpose of this study is to determine when functional outcome no longer improves following tibial plateau fracture. A patient series of operatively treated tibial plateau fractures was reviewed. Patients were evaluated using the short musculoskeletal function assessment (SMFA), range of motion (ROM) assessment, and pain levels at visual analog scale (VAS) at 3, 6, and 12 months postoperatively. Fractures were classified by the Schatzker's classification using preoperative imaging. The case series was divided into two groups based on fracture patterns. Friedman's tests were conducted to determine if there were differences in SMFA, ROM, or VAS throughout the postoperative course. A total of 117 patients with tibial plateau fractures treated operatively, with complete follow-up and without complication, were identified. Seventy-seven patients (65.8%) sustained lateral tibial plateau fractures (Schatzker's I–III). Friedman's test demonstrated significant differences in SMFA (p < 0.0005) and ROM (p < 0.0005) at the three time points. Post hoc analysis demonstrated a significant difference in SMFA (p < 0.0005) and ROM (p = 0.003) between 3 and 6 months postoperatively but no significant difference in either metric between 6 and 12 months postoperatively. Friedman's test demonstrated no significant difference in VAS postoperatively (p = 0.210). Forty patients (34.2%) sustained medial or bicondylar tibial plateau fractures (Schatzker's IV–VI). Friedman's test demonstrated significant differences in SMFA (p < 0.0005) and ROM (p < 0.0005) at the three time points. Post hoc analysis demonstrated a strong trend toward significance in SMFA between 3 and 6 months postoperatively (p = 0.088), and demonstrated a significant difference between 6 and 12 months postoperatively (p = 0.013). ROM was found to be significantly different between 3 and 6 months postoperatively (p = 0.010), but no difference was found between 6 and 12 months postoperatively (p = 0.929). Friedman's test demonstrated no significant difference in VAS postoperatively (p = 0.941). In this cohort, no significant difference in function, ROM, or pain level exists between 6 and 12 months after treatment of lateral tibial plateau fractures. However, there are significant improvements in function for at least 1 year following medial or bicondylar tibial plateau fractures.


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