The importance of GLP-1 and PYY in resistant starch's effect on body fat in mice.
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ABSTRACT:
SUBMITTER: Zhou J
PROVIDER: S-EPMC5553290 | biostudies-other | 2015 May
REPOSITORIES: biostudies-other
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Project description:ObjectiveA previous genome-wide association study linked overexpression of an ATP-binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse.MethodsA global Abcc5-/- mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon-like peptide 1 (GLP-1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme-linked immunosorbent assay.ResultsAbcc5-/- mice had decreased fat mass and increased plasma levels of GLP-1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP-1 release.ConclusionsABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP-1 secretion from enteroendocrine cells.
| S-EPMC6658130 | biostudies-literature
Project description:The prevalence of obesity in industrialized societies has become markedly elevated. In contrast, model organism research shows that reducing caloric intake below ad libitum levels provides many health and longevity benefits. Despite these benefits, few people are willing and able to reduce caloric intake over prolonged periods. Prior research suggests that mannooligosaccharide (MOS or mannan) supplementation can increase lifespan of some livestock and in rodents can reduce visceral fat without reducing caloric intake. Hence, we tested the effect of MOS supplementation as a possible calorie restriction (CR) mimetic (CRM) in mice. C57Bl/6J male mice were fed a high-fat "western" type diet with or without 1% MOS (by weight) supplementation (n = 24/group) from 8 to 20 weeks of age. Animals were housed individually and provided 95% of ad libitum food intake throughout the study. Body weight was measured weekly and body composition (lean and fat mass) measured noninvasively every 3 weeks. Individual fat depot weights were acquired by dissection at study completion. Supplementation of a high-fat diet with 1% MOS tended to reduce total food intake (mean +/- s.d.; control (CON): 293.69 +/- 10.53 g, MOS: 288.10 +/- 11.82 g; P = 0.09) during the study. Moreover, MOS supplementation had no significant effect on final body weight (CON: 25.21 +/- 2.31 g, MOS: 25.28 +/- 1.49 g; P = 0.91), total fat (CON: 4.72 +/- 0.90 g, MOS: 4.82 +/- 0.83 g; P = 0.69), or visceral fat (CON: 1.048 +/- 0.276 g, MOS: 1.004 +/- 0.247 g; P = 0.57). Contrary to previous research, MOS supplementation had no discernable effect on body weight gain or composition during this 12-week study, challenging the potential use of MOS as a CRM or body composition enhancer.
| S-EPMC2940117 | biostudies-literature
Project description:ObjectivePharmacological strategies that engage multiple mechanisms-of-action have demonstrated synergistic benefits for metabolic disease in preclinical models. One approach, concurrent activation of the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon (Gcg) receptors (i.e. triagonism), combines the anorectic and insulinotropic activities of GLP-1 and GIP with the energy expenditure effect of glucagon. While the efficacy of triagonism in preclinical models is known, the relative contribution of GcgR activation remains unassessed. This work aims to addresses that central question.MethodsHerein, we detail the design of unimolecular peptide triagonists with an empirically optimized receptor potency ratio. These optimized peptide triagonists employ a protraction strategy permitting once-weekly human dosing. Additionally, we assess the effects of these peptides on weight-reduction, food intake, glucose control, and energy expenditure in an established DIO mouse model compared to clinically relevant GLP-1R agonists (e.g. semaglutide) and dual GLP-1R/GIPR agonists (e.g. tirzepatide).ResultsOptimized triagonists normalize body weight in DIO mice and enhance energy expenditure in a manner superior to that of GLP-1R mono-agonists and GLP-1R/GIPR co-agonists.ConclusionsThese pre-clinical data suggest unimolecular poly-pharmacology as an effective means to target multiple mechanisms contributing to obesity and further implicate GcgR activation as the differentiating factor between incretin receptor mono- or dual-agonists and triagonists.
| S-EPMC9305623 | biostudies-literature
Project description:Obesity contributes to a chronic proinflammatory state, which is a known risk factor to develop immune-mediated diseases. However, its role in systemic sclerosis (SSc) remains to be elucidated. Therefore, we conducted a two-sample mendelian randomization (2SMR) study to analyze the effect of three body fat distribution parameters in SSc. As instrumental variables, we used the allele effects described for single nucleotide polymorphisms (SNPs) in different genome-wide association studies (GWAS) for SSc, body mass index (BMI), waist-to-hip ratio (WHR) and WHR adjusted for BMI (WHRadjBMI). We performed local (pHESS) and genome-wide (LDSC) genetic correlation analyses between each of the traits and SSc and we applied several Mendelian randomization (MR) methods (i.e., random effects inverse-variance weight, MR-Egger regression, MR pleiotropy residual sum and outlier method and a multivariable model). Our results show no genetic correlation or causal relationship between any of these traits and SSc. Nevertheless, we observed a negative causal association between WHRadjBMI and SSc, which might be due to the effect of gastrointestinal complications suffered by the majority of SSc patients. In conclusion, reverse causality might be an especially difficult confounding factor to define the effect of obesity in the onset of SSc.
| S-EPMC9604859 | biostudies-literature
Project description:PURPOSE:Obesity is associated with alterations in appetite, gastrointestinal hormone levels and excessive fat mass. We previously published a double-blind, placebo-controlled, randomized, 16-week trial on effects of once-daily glucagon-like peptide-1 (GLP-1) analog, liraglutide on weight, satiation, and gastric functions in obese volunteers. The aim of this substudy is to compare to placebo the effects of liraglutide on appetite, taste preference, regional body fat stores, and anthropometric measurements. METHODS:Forty obese adults received standard instruction for weight management, monthly behavioral intervention utilizing motivational interviews, and 16-week treatment of once-daily liraglutide (escalated to 3 mg SQ daily). At baseline and 16 weeks, the following were measured: appetite and taste preferences rated every 30 min for 5 h after ingesting 300 mL Ensure®; maximal tolerated volume (MTV) with a nutrient drink test; fasting and postprandial bioactive GLP-1 (7-36) and peptide YY (PYY) levels; total and regional body fat with dual-energy X-ray absorptiometry, and waist and hip circumference. RESULTS:Thirty-five participants (17 liraglutide; 18 placebo) completed the trial. Compared to placebo group, liraglutide group had significant reductions in MTV; prospective food consumption score; desire to eat something sweet, salty, savory or fatty; and an increase in perceived fullness. Postprandial plasma levels of GLP-1 decreased and PYY levels increased with liraglutide relative to baseline. Significant reductions in total body, trunk, and upper and lower body fat without reduction in lean body mass were observed. CONCLUSION:Liraglutide 3 mg SQ modulates appetite, taste preference, gut hormones, and regional body fat stores in adults with obesity without reduction in lean body mass.
| S-EPMC7105351 | biostudies-literature
Project description:Effect of Mef2 knockdown in Drosophila fat body
2016-10-13 | GSE80318 | GEO
Project description:Several environmental factors during the prenatal period transgenerationally affect the health of newborns in later life. Because low-dose antibiotics have been used for promoting the growth of crops and livestock in agriculture, humans may have ingested residual antibiotics for several decades. However, the effect of prenatal administration of low-dose antibiotics on newborns' health in later life is unclear. In the present study, we found that prenatal treatment of murine mothers with low-dose antibiotics increased the abundance of bacteria of the phylum Firmicutes and the genera Clostridium IV and XIVa in feces from pups. In addition, the body fat percentage of mice in the antibiotic-treated group was higher than those in the control group at 12 weeks of age even though all pups were fed a standard diet. The body fat percentage of all mice was correlated with the abundance of fecal bacteria of Clostridium IV and XIVa. These results predict that low-dose antibiotic administration during the prenatal period affects the gut microbiota of newborns and possibly their health in later life.
| S-EPMC5874232 | biostudies-literature
Project description:BackgroundAlthough gut hormone glucagon-like peptide 1 (GLP-1) has been widely used for treating diabetes, the extremely short half-life greatly limits its application. The purpose of this study is to explore the effects of an engineered bacteria with expression of GLP-1 on obese mice induced by high fat diet (HFD).MethodsThe engineered strain of MG1363-pMG36e-GLP-1 (M-GLP-1) was constructed and its anti-obesity effects were evaluated in vivo. The bodyweight, the morphology of adipose and liver tissue, and liver function were examined. Quantitative RT-PCR and Western blot were used to measure the expressions of the genes involved in fatty acid oxidation synthesis. The intestinal microbial diversity was detected with high-throughput sequencing analysis.ResultsThe engineered bacteria could produce GLP-1. It also significantly decreased the bodyweight and improved the glucose intolerance in the obese mice induced by HFD. Moreover, the strain also reduced the triglyceride (TG) in serum, protected liver, as well as decreased the intracellular TG in liver tissues of the obese mice. Furthermore, our results showed that the expressions of the genes including peroxisome proliferator-activated receptors α (PPARα) and its target genes were enhanced in liver tissues when mice treated with M-GLP-1. Finally, we found that the engineered strain markedly increased intestinal microbial diversity.ConclusionOur results suggested the genetically engineered bacteria that constitutively secreted GLP-1 could improve obesity and the mechanism may be related to promoting fatty acid oxidation and increasing intestinal microbial diversity of the obese mice.
| S-EPMC7959774 | biostudies-literature
Project description:modENCODE_submission_5522 This submission comes from a modENCODE project of David MacAlpine. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: Most terminally differentiated Drosophila tissues are either polyploid or polytene. Unlike normal chromosomes, where the entire chromosome must be replicated exactly once, polytene chromosomes are often differentially replicated with many regions underreplicated and some overreplicated. We will characterize five different polytene tissues using comparative genomic hybridization (CGH) to identify differentially replicated regions of each chromosome. These studies will also identify tissue specific amplicons, where the replication mediated amplification of specific loci is essential for up-regulation of mRNA levels encoding proteins critical for development. The differential replication of polytene chromosomes in Drosophila will provide a unique opportunity to understand how developmental cues and chromosomal domains influence replication initiation. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CGH. BIOLOGICAL SOURCE 1: Strain: Oregon-R Orr-Weaver(genotype : TBA outcross : TBA description : Wild-type Oregon-R population maintained by Terry Orr-Weaver. made_by : wt population ); Tissue: Fatbody; Developmental Stage: cleavage stage; Genotype: TBA; Sex: Unknown; BIOLOGICAL SOURCE 2: Strain: Oregon-R Orr-Weaver(genotype : TBA outcross : TBA description : Wild-type Oregon-R population maintained by Terry Orr-Weaver. made_by : wt population ); Tissue: Fatbody; Developmental Stage: cleavage stage; Genotype: TBA; Sex: Unknown; NUMBER OF REPLICATES: 1; EXPERIMENTAL FACTORS: Tissue Fatbody
2012-06-03 | E-GEOD-38440 | biostudies-arrayexpress
Project description:modENCODE_submission_5522 This submission comes from a modENCODE project of David MacAlpine. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: Most terminally differentiated Drosophila tissues are either polyploid or polytene. Unlike normal chromosomes, where the entire chromosome must be replicated exactly once, polytene chromosomes are often differentially replicated with many regions underreplicated and some overreplicated. We will characterize five different polytene tissues using comparative genomic hybridization (CGH) to identify differentially replicated regions of each chromosome. These studies will also identify tissue specific amplicons, where the replication mediated amplification of specific loci is essential for up-regulation of mRNA levels encoding proteins critical for development. The differential replication of polytene chromosomes in Drosophila will provide a unique opportunity to understand how developmental cues and chromosomal domains influence replication initiation. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
2012-06-04 | GSE38440 | GEO