Dataset Information

Alterations in energy balance following exenatide administration.

ABSTRACT: Exenatide is a medication similar in structure and effect to native glucagon-like peptide-1, an incretin hormone with glucose-lowering properties. The aim of the study was to measure the change in total energy expenditure (TEE) and body composition during exenatide administration and by deduction the relative contributions of energy expenditure and energy intake to exenatide-induced weight loss. Forty-five obese (body mass index, 30-40 kg·m?²) subjects were identified. After exclusion criteria application, 28 subjects entered into the study and 18 subjects (12 female, 6 male) completed the study, which consisted of 6 visits over 14 weeks and injection of exenatide for an average of 84 ± 5 days. Respiratory gas analysis and doubly labeled water measurements were performed before initiation of exenatide and after approximately 3 months of exenatide administration. The average weight loss from the beginning of injection period to the end of the study in completed subjects was 2.0 ± 2.8 kg (p = 0.01). Fat mass declined by 1.3 ± 1.8 kg (p = 0.01) while the fat-free mass trended downward but was not significant (0.8 ± 2.2 kg, p = 0.14). There was no change in weight-adjusted TEE (p = 0.20), resting metabolic rate (p = 0.51), or physical activity energy expenditure (p = 0.38) and no change in the unadjusted thermic effect of a meal (p = 0.37). The significant weight loss because of exenatide administration was thus the result of decreasing energy intake. In obese nondiabetic subjects, exenatide administration did not increase TEE and by deduction the significant weight loss and loss of fat mass was due to decreased energy intake.

SUBMITTER: Bradley DP

PROVIDER: S-EPMC3623676 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alterations in energy balance following exenatide administration.

Bradley David P DP Kulstad Roger R Racine Natalie N Shenker Yoram Y Meredith Melissa M Schoeller Dale A DA

Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 20120626 5

Exenatide is a medication similar in structure and effect to native glucagon-like peptide-1, an incretin hormone with glucose-lowering properties. The aim of the study was to measure the change in total energy expenditure (TEE) and body composition during exenatide administration and by deduction the relative contributions of energy expenditure and energy intake to exenatide-induced weight loss. Forty-five obese (body mass index, 30-40 kg·m⁻²) subjects were identified. After exclusion criteria a ...[more]

PMID: 22735035

Similar Datasets

Project description:ObjectiveThe hypothalamic control of energy balance is regulated by a complex network of neuropeptide-releasing neurons. Although the effect of these neuropeptides on individual aspects of energy homoeostasis has been studied, the coordinated response of these effects has not been comprehensively investigated. We have simultaneously monitored a number of metabolic parameters following intracerebroventricular (ICV) administration of 1 and 3 nmol of neuropeptides with established roles in the regulation of feeding, activity and metabolism. Ad libitum- fed rats received the orexigenic neuropeptides neuropeptide Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin-A. Overnight-food-deprived rats received an ICV injection of the anorectic peptides alpha-melanocyte-stimulating hormone (MSH), corticotrophin-releasing factor (CRF) or neuromedin U (NMU).ResultsOur results reveal the temporal sequence of the effects of these neuropeptides on both energy intake and expenditure, highlighting key differences in their function as mediators of energy balance. NPY and AgRP increased feeding and decreased oxygen consumption, with the effects of AgRP being more prolonged. In contrast, orexin-A increased both feeding and oxygen consumption, consistent with an observed increase in activity. The potent anorexigenic effects of CRF were accompanied by a prolonged increase in activity, whereas NMU injection resulted in significant but short-lasting inhibition of food intake, ambulatory activity and oxygen consumption. alpha-MSH injection resulted in significant increases in both ambulatory activity and oxygen consumption, and reduced food intake following administration of 3 nmol of the peptide.ConclusionWe have for the first time, simultaneously measured several metabolic parameters following hypothalamic administration of a number of neuropeptides within the same experimental system. This work has shown the interrelated effects of these neuropeotides on activity, energy expenditure and food intake, thus facilitating comparison between the different hypothalamic systems.

Project description:BACKGROUND:Negative energy balance (NEB), an altered metabolic state, occurs in early postpartum dairy cattle when energy demands to support lactation exceed energy intake. During NEB the liver undergoes oxidative stress and increased breakdown of fatty acids accompanied by changes in gene expression. It is now known that micro RNAs (miRNA) can have a role in mediating such alterations in gene expression through repression or degradation of target mRNAs. miRNA expression is known to be altered by metabolism and environmental factors and miRNAs are implicated in expression modulation of metabolism related genes. RESULTS:miRNA expression was profiled in the liver of moderate yielding dairy cattle under severe NEB (SNEB) and mild NEB (MNEB) using the Affymetrix Gene Chip miRNA_2.0 array with 679 probe sets for Bos-taurus miRNAs. Ten miRNAs were found to be differentially expressed using the 'samr' statistical package (delta = 0.6) at a q-value FDR of < 12%. Five miRNAs including miR-17-5p, miR-31, miR-140, miR-1281 and miR-2885 were validated using RT-qPCR, to be up-regulated under SNEB. Liver diseases associated with these miRNAs include non-alcoholic fatty liver (NAFLD) and hepatocellular carcinoma (HCC). miR-140 and miR-17-5p are known to show differential expression under oxidative stress. A total of 32 down-regulated putative target genes were also identified among 418 differentially expressed hepatic genes previously reported for the same animal model. Among these, GPR37 (G protein-coupled receptor 37), HEYL (hairy/enhancer-of-split related with YRPW motif-like), DNJA1, CD14 (Cluster of differentiation 14) and GNS (glucosamine (N-acetyl)-6-sulfatase) are known to be associated with hepatic metabolic disorders. In addition miR-140 and miR-2885 have binding sites on the most down-regulated of these genes, FADS2 (Fatty acid desaturase 2) which encodes an enzyme critical in lipid biosynthesis. Furthermore, HNF3-gamma (Hepatocyte nuclear factor 3-gamma), a hepatic transcription factor (TF) that is involved in IGF-1 expression regulation and maintenance of glucose homeostasis is a putative target of miR-31. CONCLUSIONS:This study shows that SNEB affects liver miRNA expression and these miRNAs have putative targets in hepatic genes down-regulated under this condition. This study highlights the potential role of miRNAs in transcription regulation of hepatic gene expression during SNEB in dairy cattle.

Project description:The T helper 17 (Th17)/T regulatory (Treg) cell imbalance is involved in the course of obesity and type 2 diabetes mellitus (T2DM). In the current study, the exact role of glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on regulating the Th17/Treg balance and the underlying molecular mechanisms are investigated in obese diabetic mice model. Metabolic parameters were monitored in db/db mice treated with/without exenatide during 8-week study period. The frequencies of Th17 and Treg cells from peripheral blood and pancreas in db/db mice were assessed. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Forkhead box O1 (FoxO1) pathway in Th17 and Treg cells from the spleens of male C57BL/6J mice was detected by western blotting. In addition, the expression of glucagon-like peptide-1 receptor (GLP-1R) in peripheral blood mononuclear cells (PBMCs) of male C57BL/6J mice was analyzed. Exenatide treatment improved β-cell function and insulitis in addition to glucose, insulin sensitivity and weight. Increased Th17 and decreased Treg cells in peripheral blood were present as diabetes progressed while exenatide corrected this imbalance. Progressive IL-17 + T cell infiltration of pancreatic islets was alleviated by exenatide intervention. In vitro study showed no significant difference in the level of GLP-1R expression in PBMCs between control and palmitate (PA) groups. In addition, PA could promote Th17 but suppress Treg differentiation along with down-regulating the phosphorylation of PI3K/Akt/FoxO1, which was reversed by exenatide intervention. FoxO1 inhibitor AS1842856 could abrogate all these effects of exenatide against lipid stress. Exenatide could restore systemic Th17/Treg balance via regulating FoxO1 pathway with the progression of diabetes in db/db mice. The protection of pancreatic β-cell function may be partially mediated by inhibiting Th17 cell infiltration into pancreatic islets, and the resultant alleviation of islet inflammation.

Project description:Background and objectivesTraumatic brain injury (TBI) is one of the leading causes of death and disability in children and adolescents. Young TBI patients suffer from gross motor deficits, such as postural control deficits, which can severely compromise their daily life activities. However, little attention has been devoted to uncovering the underlying white matter changes in response to training in TBI. In this study, we used longitudinal fixel-based analysis (FBA), an advanced diffusion imaging analysis technique, to investigate the effect of a balance training program on white matter fibre density and morphology in a group of young TBI patients.MethodsYoung patients with moderate-to-severe TBI (N = 17, 10 females, mean age = 13 ± 3 years) and age-matched controls (N = 17) underwent a home-based balance training program. Diffusion MRI scans together with gross motor assessments, including the gross motor items of the Bruininks-Oseretsky Test of Motor Proficiency, the Activities-Specific Balance Confidence (ABC) Scale, and the Sensory Organization Test (SOT) were administered before and at completion of 8-weeks of training. We used FBA to compare microstructural differences in fibre density (FD), macrostructural (morphological) changes in fibre cross-section (FC), and the combined FD and FC (FDC) metric across the whole brain. We then performed a longitudinal analysis to test whether training restores the white matter in the regions found to be damaged before treatment.ResultsWhole-brain fixel-based analysis revealed lower FD and FC in TBI patients compared to the control group across several commissural tracts, association fibres and projection fibres, with FD reductions of up to 50%. Following training, TBI patients showed a significant interaction effect between Group and Time for the SOT test, as well as significant increases in macrostructural white matter (i.e., FC & FDC) in left sensorimotor tracts. The amount of change in FC and FDC over time was, however, not associated with behavioural changes.DiscussionOur fixel-based findings identified both microstructural and macrostructural abnormalities in young TBI patients. The longitudinal results provide a deeper understanding of the neurobiological mechanisms underlying balance training, which will allow clinicians to make more effective treatment decisions in everyday clinical practice with brain-injured patients.

Dataset Information

Alterations in energy balance following exenatide administration.

Publications

Alterations in energy balance following exenatide administration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets