Fibroblast Growth Factor 21 as a Potential Biomarker for Improved Locomotion and Olfaction Detection Ability after Weight Reduction in Obese Mice.
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ABSTRACT:
SUBMITTER: Power Guerra N
PROVIDER: S-EPMC8470262 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Obesity is a significant cause of functional limitations in older adults; yet, concerns that weight reduction could diminish muscle along with fat mass have impeded progress toward an intervention. Meal-based enhancement of protein intake could protect function and/or lean mass but has not been studied during geriatric obesity reduction.In this 6-month randomized controlled trial, 67 obese (body mass index ?30kg/m(2)) older (?60 years) adults with a Short Physical Performance Battery score of 4-10 were randomly assigned to a traditional (Control) weight loss regimen or one with higher protein intake (>30g) at each meal (Protein). All participants were prescribed a hypo-caloric diet, and weighed and provided dietary guidance weekly. Physical function (Short Physical Performance Battery) and lean mass (BOD POD), along with secondary measures, were assessed at 0, 3, and 6 months.At the 6-month endpoint, there was significant (p < .001) weight loss in both the Control (-7.5±6.2kg) and Protein (-8.7±7.4kg) groups. Both groups also improved function but the increase in the Protein (+2.4±1.7 units; p < .001) was greater than in the Control (+0.9±1.7 units; p < .01) group (p = .02).Obese, functionally limited older adults undergoing a 6-month weight loss intervention with a meal-based enhancement of protein quantity and quality lost similar amounts of weight but had greater functional improvements relative to the Control group. If confirmed, this dietary approach could have important implications for improving the functional status of this vulnerable population (ClinicalTrials.gov identifier: NCT01715753).
| S-EPMC5018561 | biostudies-literature
Project description:Fibroblast growth factor 21 (FGF21) ameliorates steatohepatitis but is increased in humans with fatty liver, potentially due to compensatory mechanisms and/or FGF21 resistance. Further, animal models suggest that GH increases serum FGF21. Tesamorelin, a growth hormone releasing hormone agonist, reduces liver fat in HIV-infected individuals. The objectives of this study were to investigate changes in FGF21 during tesamorelin treatment, to elucide the interplay between FGF21, GH augmentation, and liver fat reduction in humans.50 HIV-infected men and women with increased abdominal adiposity participated in this randomized, placebo-controlled trial of tesamorelin, 2mg vs. identical placebo daily for six months. Fasting laboratory measures, liver fat by 1H-magnetic resonance spectroscopy, and visceral adipose tissue (VAT) by computed tomography were obtained. Euglycemic hyperinsulinemic clamp was performed in a randomly selected subset.At baseline, serum log10 FGF21 was significantly associated with log10 liver fat (r=0.32, p=0.03). Log10 FGF21 tended to decrease in the tesamorelin group compared to placebo (p=0.06). Among the entire cohort, reductions in FGF21 were significantly associated with reductions in liver fat (?=0.41, p=0.01), log10 gamma glutamyl tran speptidase (GGT, r=0.40, p=0.009), and FIB4 index (r=0.37, p=0.02).In HIV-infected individuals, FGF21 is significantly positively associated with liver fat. FGF21 decreases in association with reductions in liver fat, GGT, and FIB4, suggesting that FGF21 is upregulated in the context of steatosis and steatohepatitis and is reduced when these conditions improve. Moreover, these data suggest that tesamorelin improves liver fat via pathways other than increasing serum FGF21.clinicaltrials.govNCT01263717.
| S-EPMC5705434 | biostudies-literature
Project description:Behavioral therapies aimed at reducing excess body fat result in limited fat loss after dieting. To understand the causes for maintenance of adiposity, high-fat (HF) diet-induced obese (DIO) mice were switched to a low-fat chow diet, and the effects of chow on histological and molecular alterations of adipose tissue and metabolic parameters were examined. DIO mice reduced and stabilized their body weights after being switched to chow (HF-chow), but retained a greater amount of adiposity than chow-fed mice. Reduction in adipocyte volume, not number, caused a decrease in fat mass. HF-chow mice showed normalized circulating insulin and leptin levels, improved glucose tolerance, and reduced inflammatory status in white adipose tissue (WAT). Circulating leptin levels corrected for fat mass were lower in HF-chow mice. Leptin administration was used to test whether reduced leptin level of HF-chow mice inhibited further fat loss. Leptin treatment led to an additional reduction in adiposity. Finally, HF-HF mice had lower mRNA levels of beta(3) adrenergic receptor (beta(3)-AR) in epididymal WAT (EWAT) compared to chow-fed mice, and diet change led to an increase in the WAT beta(3)-AR mRNA levels that were similar to the levels of chow-fed mice, suggesting an elevation in sympathetic activation of WAT during diet switch relative to HF-HF mice leading to the reduced leptin level and proinflammatory cytokine content. In summary, HF-chow mice were resistant to further fat loss due to leptin insufficiency. Diet alteration from HF to low fat improved metabolic state of DIO mice, although their adiposity was defended at a higher level.
| S-EPMC4864426 | biostudies-literature
Project description:BackgroundDespite evidence that inflammation and metabolism play a crucial role in colorectal carcinogenesis, there have been few studies on the association of inflammatory and metabolic protein biomarkers in various stages of colorectal carcinogenesis.MethodsNinety-two inflammatory and metabolic biomarkers were measured in plasma samples of participants of screening colonoscopy. Markers identified to be significantly associated with the presence of advanced colorectal neoplasia (ACN) in a discovery set (n = 204) were validated in an independent replication set (n = 422). Adjusted associations with the presence of non-advanced adenomas (NAA), advanced precancerous lesions (APL) and colorectal cancer (CRC) were quantified by multiple logistic regression.ResultsOut of the 92 inflammatory proteins, 72 markers were evaluable and 8 showed statistically significant associations with the odds of ACN after full adjustment for potential risk factors for CRC in the discovery set. One of these, fibroblast growth factor 21 (FGF-21), could be validated in the replication set. The multivariable-adjusted odds ratio (OR) reached 2.65 (95% CI, 1.50-4.81) for individuals with FGF-21 levels within the highest tertile, compared to those within the lowest tertile (Ptrend across tertiles = 0.001). Separate models revealed fully adjusted ORs for NAA, APL and CRC of 2.99 (95% CI, 1.45-6.58, Ptrend = 0.005), 2.24 (95% CI, 1.18-4.44, Ptrend = 0.021) and 3.92 (95% CI, 1.51-12.18, Ptrend = 0.003), respectively.ConclusionsCirculating FGF-21 level is associated with increased risk of early and late stages of colorectal carcinogenesis, supporting a role of inflammation and metabolism at all stages of colorectal carcinogenesis, and suggesting potential use of this biomarker for risk stratification in CRC screening.
| S-EPMC6265243 | biostudies-literature
Project description:BackgroundThere is increasing evidence that long-term complications in organic acidemias are caused by impaired mitochondrial metabolism. Currently, there is no specific biomarker to monitor mitochondrial dysfunction in organic acidemias. Serum fibroblast growth factor 21 (FGF-21) is a biomarker for mitochondrial disease and could be a candidate to monitor mitochondrial function in the deleterious course of disease.MethodsData of 17 patients with classical organic acidemias (11 propionic acidemia (PA), four methylmalonic acidemia (MMA) and two isovaleric acidemia (IVA) patients) were included. The clinical course was evaluated; metabolic decompensations and long-term complications were correlated with plasma FGF-21 levels. Cardiomyopathy, prolonged QT interval, renal failure, and optic neuropathy were defined as long-term complications.ResultsPatients ages ranged from 16 months up to 32 years. Serious long-term complications occurred in eight patients (five PA and three MMA patients). In MMA and PA patients plasma FGF-21 levels during stable metabolic periods were significantly higher in patients with long-term complications (Mdn = 2556.0 pg/ml) compared to patients without (Mdn = 287.0 pg/ml). A median plasma FGF-21 level above 1500 pg/ml during a stable metabolic period, measured before the occurrence of long-term complications, had a positive predictive value of 0.83 and a negative predictive value of 1.00 on long-term complications in MMA and PA patients.ConclusionThis study demonstrates the potential role of FGF-21 as a biomarker for long-term complications in classical organic acidemias, attributed to mitochondrial dysfunction.
| S-EPMC6327009 | biostudies-literature
Project description:We hypothesised that epigenetics may play an important role in mediating fibroblast growth factor 21 (FGF21) resistance in obesity. We aimed to evaluate DNA methylation changes and miRNA pattern in obese subjects associated with high serum FGF21 levels. The study included 136 participants with BMI 27-45 kg/m2. Fasting FGF21, glucose, insulin, GIP, lipids, adipokines, miokines and cytokines were measured and compared in high serum FGF21 (n = 68) group to low FGF21 (n = 68) group. Human DNA Methylation Microarrays were analysed in leukocytes from each group (n = 16). Expression of miRNAs was evaluated using quantitative PCR-TLDA. The study identified differentially methylated genes in pathways related to glucose transport, insulin secretion and signalling, lipid transport and cellular metabolism, response to nutrient levels, thermogenesis, browning of adipose tissue and bone mineralisation. Additionally, it detected transcription factor genes regulating FGF21 and fibroblast growth factor receptor and vascular endothelial growth factor receptor pathways regulation. Increased expression of hsa-miR-875-5p and decreased expression of hsa-miR-133a-3p, hsa-miR-185-5p and hsa-miR-200c-3p were found in the group with high serum FGF21. These changes were associated with high FGF21, VEGF and low adiponectin serum levels. Our results point to a significant role of the epigenetic regulation of genes involved in metabolic pathways related to FGF21 action.
| S-EPMC7926457 | biostudies-literature
Project description:BackgroundFibroblast growth factor 21 (FGF21) is deemed to play an important role in kidney outcomes, while the association between FGF21 and various kidney diseases remains largely unclear and inconsistent. Therefore, we conducted this meta-analysis to find out the role of FGF21 in various renal diseases.MethodsThe outcome indicator of our study was assessed by the pooled standard mean difference (SMD) with 95% confidence intervals (CIs) which were calculated by random-effect model analysis. The risk of bias was assessed by Non-Randomized Studies of Interventions (ROBINS-I) tool. Funnel plot combined with Egger's and Begg's tests was performed to estimate the publication bias that existed in the study.ResultsA total of 28 eligible studies with 19348 participants were included in our research. The agreement between authors reached a kappa-value of 0.88. Overall, the serum FGF21 level was strongly higher in CKD patients (SMD = 0.97 (ng/L); 95% CI, 0.70-1.24 (ng/L)) and the renal outcomes in T2DM patients (SMD = 0.54 (ng/L); 95% CI, 0.39-0.70 (ng/L)) compared with the control group. Consistent with this, the incidence of CKD (OR = 2.56; 95% CI, 1.72-3.81) and the incidence of renal outcomes (OR = 1.63; 95% CI, 1.31-2.01) in T2DM patients was significantly higher in the patients with high FGF21 concentration, indicating that high serum FGF21 level may predict the incidence of CKD and the renal outcomes in T2DM patients.ConclusionSerum FGF21 may be one of the strong predictors for various kidney diseases including the progression of CKD and the hard renal outcomes in type 2 diabetes patients, but more large-scale clinical research are needed to confirm this finding.
| S-EPMC10071947 | biostudies-literature
Project description:The formation and pollution of particulate matter (PM), a side effect of rapid industrialization and urbanization, is considered a global issue. However, various plant species are able to effectively capture and reduce atmospheric PM concentrations. We investigated the indoor growth and morphology of 21 indigenous Korean evergreen species at low light intensities to ascertain their ability to reduce PM of aerosol particles in a closed acrylic chamber. The decrease in PM mass concentration differed significantly across species, with a significant correlation (8 h; p < 0.001). The reduction in the mass concentration of PM differed with particle size and across species. The highest reduction of PM2.5 occurred after 8 h with Dryopteris lacera (86.8%), Ilex × wandoensis (84.9%), Machilus thunbergii (84.3%), and Rhododendron brachycarpum (84.0%). Reduction of PM10 after 8 h was highest with Cephalotaxus harringtonii (98.3%), I. × wandoensis (98.5%), M. thunbergii (98.5%), and R. brachycarpum (98.3%). Plant morphological characteristics (category, plant height, leaf shape, leaf area) and relative humidity were closely related to the decrease in PM mass concentration. In conclusion, our findings can be used to identify Korean plant species that can reduce PM concentration and are suitable for indoor use.
| S-EPMC8466017 | biostudies-literature
Project description:To profile the expression of circulating miRNAs in a mouse model of diet-induced obesity (DIO) with subsequent weight-reduction with low-fat diet (LFD), eighteen C57BL/6 male mice were grouped into three subgroups as: (1) Control: the mice fed with the standard AIN-76A (fat: 11.5 kcal%) diet for 12 wks; (2) DIO: the mice fed with 58 kcal% high-fat diet for 12 wks; (3) DIO+LFD: the mice fed with high-fat diet for 8 wks to induce obesity, then changed to 10.5 kcal% low-fat diet for subsequent 4 wks. C57BL/6 mice were purchased from BioLasco (Taipei, Taiwan). All housing conditions were maintained, and surgical procedures, including analgesia, were performed in an Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC)-accredited SPF facility according to national and institutional guidelines. In this experiment, eighteen C57BL/6 wild type male mice were randomly grouped into three subgroups (n=6 in each group): (1) Control: the control mice were fed ad libitum a standard AIN-76A (fat: 11.5 kcal%) diet for 12 wks; (2) DIO: the mice were fed ad libitum a 58 kcal% HFD (D12331; Research Diets Inc., New Brunswick, NJ) for 12 wks to induce obesity; (3) DIO+LFD: the mice fed ad libitum a 58 kcal% HFD (D12331) for 8 wks to induce obesity, then continued the feeding of 10.5 kcal% LFD (D 12329; Research Diets Inc.) for additional 4 wks. Weight measurements were performed on a weekly basis to for these three groups of mice. Evaluation of blood glucose levels was performed at the beginning and in the end of the experiment to confirm that the HFD-fed mice developed an obese and insulin resistant phenotype. After the end of experiment at 12w, all mice were killed. The abdominal WAT of each mice was removed and weighted. Paraffin-embedded abdominal WAT was sectioned at 5 M-NM-<m and stained with hematoxylin and eosin to measure mean adipocyte area. A volume of 1 mL of whole blood was collected into a plain tube and allowed to clot for 1 hour. The sera samples were aliquoted after centrifugation at 3,000 M-CM-^W g for 10 minutes and stored at M-bM-^HM-^R80M-BM-0C until further analysis.
2014-09-03 | E-GEOD-61005 | biostudies-arrayexpress
Project description:To profile the expression of circulating miRNAs in a mouse model of diet-induced obesity (DIO) with subsequent weight-reduction with low-fat diet (LFD), eighteen C57BL/6 male mice were grouped into three subgroups as: (1) Control: the mice fed with the standard AIN-76A (fat: 11.5 kcal%) diet for 12 wks; (2) DIO: the mice fed with 58 kcal% high-fat diet for 12 wks; (3) DIO+LFD: the mice fed with high-fat diet for 8 wks to induce obesity, then changed to 10.5 kcal% low-fat diet for subsequent 4 wks.
2014-09-03 | GSE61005 | GEO