Modeling energy intake and body weight effects of a long-acting amylin analogue

AbstractThe inhibitory effect of anti-obesity drugs on energy intake (EI) is counter-acted by feedback regulation of the appetite control circuit leading to drug tolerance. This complicates the design and interpretation of EI studies in rodents that are used for anti-obesity drug development. Here, we investigated a synthetic long-acting analogue of the appetite-suppressing peptide hormone amylin (LAMY) in lean and diet-induced obese (DIO) rats. EI and body weight (BW) were measured daily and LAMY concentrations in plasma were assessed using defined time points following subcutaneous administration of the LAMY at different dosing regimens. Overall, 6 pharmacodynamic (PD) studies including a total of 173 rats were considered in this evaluation. Treatment caused a dose-dependent reduction in EI and BW, although multiple dosing indicated the development of tolerance over time. This behavior could be adequately described by a population model including homeostatic feedback of EI and a turnover model describing the relationship between EI and BW. The model was evaluated by testing its ability to predict BW loss in a toxicology study and was utilized to improve the understanding of dosing regimens for obesity therapy. As such, the model proved to be a valuable tool for the design and interpretation of rodent studies used in anti-obesity drug development.
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

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AbstractFat-mass and obesity-associated protein (Fto) plays important roles in energy metabolism. It also acts as a demethylase and is most abundantly found in the brain. In the present study, we examined the spatial and temporal changes of Fto immunoreactivity after five minutes of transient forebrain ischemia in the hippocampus. In the control group, Fto immunoreactivity was mainly observed in the nucleus of pyramidal cells in the CA1 and CA3 regions as well as the polymorphic layer, granule cell layer, and subgranular zone of the dentate gyrus. Fto immunoreactivity was transiently, but not significantly, increased in th...
Source: Metabolic Brain Disease - Category: Neurology Source Type: research
Conclusion: There was a high prevalence of MetS and abnormal ECG among the studied population. Abnormal ECG findings were more common in men with no differential association in people with or without MetS. However, a significant association existed between certain components of MetS and ECG abnormalities in men only. Male gender and HDLc were independent predictors of ECG Abnormalities.Keyword: Electrocardiography, metabolic syndrome, africans.
Source: African Health Sciences - Category: African Health Source Type: research
Background: The 2017 ACC/AHA Guideline categorized blood pressure into 4 levels:normal (SBP
Source: African Health Sciences - Category: African Health Source Type: research
Introduction: Hypertension is a cause and consequence of chronic kidney disease globally. The other factors that work in concert with hypertension to cause CKD are yet to be clearly elucidated. Studies have identified proteinuria, dyslipidemia, obesity, smoking and family history of CKD as renal risk factors. Due to the high morbidity and mortality associated with occurrence of CKD including the enormous financial burden involved in its management, the knowledge of prevention and understanding of the risk factors for development of CKD is highly essential. Therefore, Identifying well defined risk factors that display stron...
Source: African Health Sciences - Category: African Health Source Type: research
Conclusion: The current study provides evidence that aerobic exercise is more appropriate than resisted exercise training in modulating inflammatory cytokines and quality of life among obese post-menopausal women.Keywords: Aerobic exercise; resisted exercises; inflammatory cytokine; quality of life; obesity; menopause.
Source: African Health Sciences - Category: African Health Source Type: research
Conclusion: Women who use CAM usually use it with information that is out of the knowledge of health profession and lack of information. It is recommended to carry out extensive studies for CAM methods and the mechanisms of action that women use.Keywords: Menopause, hot flashes, complementary and alternative medicine.
Source: African Health Sciences - Category: African Health Source Type: research
Background: Malnutrition (under and overnutrition) presents significant threats to child health. The co-existence of under and overnutrition in a population is increasingly being described in the literature .Objective: To identify the prevalence of malnutrition among under-five children in Enugu metropolis.Methods: A cross-sectional study of pre-primary school children conducted from January to May 2016. using stratified sampling technique. Caregiver-administered questionnaire was used to obtain relevant information. Weights and heights were measured using a standard weight scale and stadiometer/ length mat respectively. W...
Source: African Health Sciences - Category: African Health Source Type: research
ConclusionThe results suggest that weight perception explains part of the relationship between physical activity and life satisfaction in adolescents and that these effects vary as a function of age and sex.Graphical abstract
Source: Journal of Sport and Health Science - Category: Sports Medicine Source Type: research
In this study, we examined 1,182 subjects (658 men and 524 women, 62.3 ± 11.7 years on average) who underwent voluntary health check-ups and sought to determine the optimal cut-off value of WC for predicting carotid IMT thickness. Receiver operating characteristic curve analysis of WC was utilized to predict high carotid IMT (defined as carotid IMT ≥ 1.1 mm). We determined that the appropriate WC cut-off value was a WC ≥ 79 cm for men and women. There was a statistically significant difference in the prevalence of high carotid IMT between WC ≥ 79 cm and WC
Source: International Heart Journal - Category: Cardiology Tags: Int Heart J Source Type: research
Authors: Wu CC, Chang CS, Hsu CC, Wang CP, Tsai IT, Lu YC, Houng JY, Chang CC, Chung FM, Lee YJ, Hung WC Abstract Low-circulating levels of adiponectin (ADPN) are associated with obesity, diabetes mellitus, and coronary artery disease. On the contrary, some studies have demonstrated a link between relatively high levels of plasma ADPN and heart failure, atrial fibrillation, and adverse outcome. However, little is known about the relationship between ADPN level and prolonged QT interval. The aim of this study was to investigate the association between plasma ADPN levels and prolonged QT interval in patients with sta...
Source: International Heart Journal - Category: Cardiology Tags: Int Heart J Source Type: research
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