Dataset Information

Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet.

ABSTRACT: This study aims to investigate the effect of feeding low-fat diet (LFD) to diet-induced obesity (DIO) mice lacking TLR5 (TLR5(-/-)), which have a tendency to develop glucose intolerance with increased adiposity, compared to that in C57BL/6 mice.TLR5(-/-) and C57BL/6 male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal%) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal% high-fat diet (HFD) for 12 weeks; and (3) diet, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal% LFD for 4 weeks. The glucose intolerance in DIO TLR5(-/-) mice was more significant than that in DIO C57BL/6 mice and was not attenuated by a switch to the LFD. Weight-reduction with LFD had significantly decreased the epididymal fat mass in C57BL/6 mice but not in TLR5(-/-) mice. In addition, the LFD-fed TLR5(-/-) mice showed significantly higher expression of ghrelin in the serum and resistin in the epididymal fat than that in C57BL/6 mice.This study demonstrated that TLR5 gene knockout impairs some effects of weight-reduction in DIO.

SUBMITTER: Wu SC

PROVIDER: S-EPMC4670872 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet.

Wu Shao-Chun SC Rau Cheng-Shyuan CS Lu Tsu-Hsiang TH Tzeng Siou-Ling SL Wu Yi-Chan YC Wu Chia-Jung CJ Lin Chia-Wei CW Hsieh Ching-Hua CH

Mediators of inflammation 20151123

<h4>Background</h4>This study aims to investigate the effect of feeding low-fat diet (LFD) to diet-induced obesity (DIO) mice lacking TLR5 (TLR5(-/-)), which have a tendency to develop glucose intolerance with increased adiposity, compared to that in C57BL/6 mice.<h4>Results</h4>TLR5(-/-) and C57BL/6 male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal%) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal% high-fat diet (HFD) for 12 weeks; an ...[more]

PMID: 26681840

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Project description:Background: This study aimed at assessing the effect of a low-fat diet (LFD) in obese mice lacking toll?like receptors (Tlr) and understanding the expression and regulation of microRNAs during weight reduction. Methods: C57BL/6, Tlr5-/-, Tlr2-/- and Tlr4-/- mice were used in this study. A group of mice were fed with a high-fat diet (HFD) (58% kcal) for 12 weeks to induce obesity (diet-induced obesity, DIO). Another group that had been fed with HFD for eight weeks (obese mice) were switched to a low-fat diet (LFD) (10.5% kcal) for the next four weeks to reduce their body weight. The control mice were fed with a standard AIN-76A diet for the entire 12 weeks. The body weight of the mice was measured weekly. At the end of the experiment, epididymal fat weight and adipocyte size were measured. The differentially expressed miRNAs in the fat tissue was determined by next-generation sequencing with real-time quantitative reverse transcription polymerase chain reaction (RT?qPCR). Target prediction and functional annotation of miRNAs were performed using miRSystem database. Results: Switching to LFD significantly reduced the body weight and epididymal fat mass in the HFD-fed C57BL/6 and Tlr5-/- mice but not in Tlr2-/- and Tlr4-/- mice. Weight reduction significantly decreased the size of adipocytes in C57BL/6 but not in the Tlr knockout mice. In Tlr2-/- and Tlr4-/- mice, feeding with HFD and the subsequent weight reduction resulted in an aberrant miRNA expression in the epididymal fat tissue unlike in C57BL/6 and Tlr5-/-. However, target prediction and functional annotation by miRSystem database revealed that all the top 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways of the dysregulated miRNAs during weight reduction in the C57BL/6 mice were also found in the regulated pathways of Tlr5-/-, Tlr2-/-, and Tlr4-/- strains. However, among these pathways, gene sets involved in arginine and proline metabolism and glutathione metabolism were mainly involved in the Tlr knockout mice but not in the C57BL/6 mice. Conclusions: In this study, we demonstrated that feeding of LFD leads to significant body weight reduction in C57BL/6 and Tlr5-/- mice, but not in Tlr2-/- and Tlr4-/- mice. Significant reduction in the size of adipocytes of epididymal fat was only found in C57BL/6, but not in Tlr5-/-, Tlr2-/-, and Tlr4-/- mice. The dysregulated miRNAs in Tlr2-/- and Tlr4-/- mice were different from those in C57BL/6 and Tlr5-/- strains. Among those miRNA-regulated pathways, arginine and proline metabolism as well as glutathione metabolism may have important roles in the Tlr knockout mice rather than in C57BL/6 mice.

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.

Dataset Information

Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet.

Publications

Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet.

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