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. 2019 Oct 11;294(41):15014-15024.
doi: 10.1074/jbc.RA119.009936. Epub 2019 Aug 19.

Taurine-mediated browning of white adipose tissue is involved in its anti-obesity effect in mice

Ying-Ying Guo  1 , Bai-Yu Li  1 , Wan-Qiu Peng  1 , Liang Guo  2 , Qi-Qun Tang  3
Affiliations

Taurine-mediated browning of white adipose tissue is involved in its anti-obesity effect in mice

Ying-Ying Guo et al. J Biol Chem. .

Abstract

Taurine, a nonprotein amino acid, is widely distributed in almost all animal tissues. Ingestion of taurine helps to improve obesity and its related metabolic disorders. However, the molecular mechanism underlying the protective role of taurine against obesity is not completely understood. In this study, it was found that intraperitoneal treatment of mice with taurine alleviated high-fat diet (HFD)-induced obesity, improved insulin sensitivity, and increased energy expenditure and adaptive thermogenesis of the mice. Meanwhile, administration of the mice with taurine markedly induced the browning of inguinal white adipose tissue (iWAT) with significantly elevated expression of PGC1α, UCP1, and other thermogenic genes in iWAT. In vitro studies indicated that taurine also induced the development of brown-like adipocytes in C3H10T1/2 white adipocytes. Knockdown of PGC1α blunted the role of taurine in promoting the brown-like adipocyte phenotypes in C3H10T1/2 cells. Moreover, taurine treatment enhanced AMPK phosphorylation in vitro and in vivo, and knockdown of AMPKα1 prevented taurine-mediated induction of PGC1α in C3H10T1/2 cells. Consistently, specific knockdown of PGC1α in iWAT of the HFD-fed mice inhibited taurine-induced browning of iWAT, with the role of taurine in the enhancement of adaptive thermogenesis, the prevention of obesity, and the improvement of insulin sensitivity being partially impaired. These results reveal a functional role of taurine in facilitating the browning of white adipose tissue, which depends on the induction of PGC1α. Our studies also suggest a potential mechanism for the protective role of taurine against obesity, which involves taurine-mediated browning of white adipose tissue.

Keywords: AMP-activated kinase (AMPK); UCP1; adaptive thermogenesis; adipose tissue; browning of adipose tissue; energy metabolism; insulin resistance; metabolic regulation; obesity; peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) (PPARGC1A); taurine.

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Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article

Figures

Figure 1.
Figure 1.
Taurine reduces obesity and improves insulin sensitivity in HFD-fed mice. The 6-week-old C57BL6 male mice were fed a HFD for 14 weeks before being sacrificed for analyses. During the last 5 weeks of HFD feeding, mice were administered taurine intraperitoneally (150 mg/kg per mouse, once a day) or PBS as a control. A, body weights (BW) of the mice before taurine treatment and 5 weeks after taurine treatment. B, body composition of the mice after 5 weeks of taurine treatment. C, representative H&E staining images of iWAT of the mice. Scale bar, 50 μm. D, percentage of iWAT weight relative to the whole-body weight of the mice. E, representative H&E staining images of eWAT of the mice. Scale bar, 50 μm. F, percentage of eWAT weight relative to the whole-body weight of the mice. G, plasma FFA levels of the mice after overnight fasting. H and I, glucose concentrations during an i.p. glucose tolerance test (H) or an insulin tolerance test (I). For statistical analysis, two-way analysis of variance and Bonferroni's post hoc tests were performed in A, B, H, and I, and unpaired two-tailed Student's t tests were performed in D, F, and G. For statistical analysis in D, F–I, data were compared between the PBS group and the taurine group. All values are represented as means with error bars representing S.D. *, p < 0.05; **, p < 0.01. n = 6 for each group.
Figure 2.
Figure 2.
Taurine increases energy expenditure and adaptive thermogenesis. Mice were treated as indicated in Fig. 1. A and B, whole-body oxygen consumption rate (VO2) of the mice during a 12-h light/12-h dark cycle measured in a metabolic cage (A) and the average values for 12-h light/12-h dark periods were shown in B. C and D, heat production of the mice during a 12-h light/12-h dark cycle was calculated and shown in C, and the average values for 12-h light/12-h dark periods are shown in D. E, average values of RER in the mice for a 24-h cycle were calculated from the metabolic cage data. F, rectal temperature of the mice was recorded at the indicated time points after cold exposure (4 °C). For statistical analysis, two-way analysis of variance and Bonferroni's post hoc tests were performed in B, D, and F, and unpaired two-tailed Student's t tests were performed in E. All values are represented as means with error bars representing S.D. *, p < 0.05; **, p < 0.01. n = 6 for each group.
Figure 3.
Figure 3.
Browning of iWAT and activation of a thermogenic program by taurine. Mice were treated as indicated in Fig. 1. A–C, mRNA levels of the indicated genes were determined by RT-qPCR in BAT, eWAT, and iWAT, respectively. D, Western blot analysis of the protein levels in iWAT by using the indicated antibodies. β-Actin serves as an internal control. E, IHC for UCP1 protein (brown stain) in iWAT sections of the mice. Scale bar, 50 μm. F, mtDNA copy number of iWAT. Data were normalized to the PBS-treated group. For statistical analysis, two-way analysis of variance and Bonferroni's post hoc tests were performed in A–C, and unpaired two-tailed Student's t tests were performed in F. All groups were compared with the PBS group. All values are represented as means with error bars representing S.D. *, p < 0.05; **, p < 0.01; and ***, p < 0.001. n = 6 for each group.
Figure 4.
Figure 4.
Taurine induces a brown adipocyte-like phenotype in C3H10T1/2 white adipocytes in vitro. C3H10T1/2 white adipocytes were treated with taurine at the indicated dose or with PBS as a control. After 24 h of treatment, cells were harvested for analyses. A, mRNA levels of the indicated genes were determined by using RT-qPCR. Data were normalized to the PBS group. B, cell lysates were then subjected to Western blotting by using the indicated antibodies. β-Actin serves as an internal control. C, cells were stained with MitoTracker Green (MTG) and 4′,6-diamidino-2-phenylindole (DAPI), and representative images are shown. Scale bar, 100 μm. Staining was performed after 24 h of treatment with PBS or 1 mm taurine. D, basal OCR was measured and shown. For statistical analysis, two-way analysis of variance and Bonferroni's post hoc tests were performed in A, and unpaired two-tailed Student's t tests were performed in D. All groups were compared with the PBS group. All values are represented as means with error bars representing S.D. *, p < 0.05; **, p < 0.01; ***, p < 0.001. n = 5 for each group.
Figure 5.
Figure 5.
Knockdown of PGC1α blunts the role of taurine in promoting the brown adipocyte-like features in C3H10T1/2 adipocytes. C3H10T1/2 white adipocytes were infected with adenovirus harboring the shRNA against LacZ (shLacZ) or shRNA against PGC1α (shPGC1α). After 48 h of adenovirus infection, cells were treated with taurine at a final concentration of 1 mm or with PBS as a control. After 24 h of treatment, cells were harvested for analyses. A, mRNA levels of the indicated genes were determined by using RT-qPCR. Data were normalized to PBS + shLacZ group. B, cell lysates were then subjected to Western blotting by using the indicated antibodies. β-Actin serves as an internal control. C, cells were stained with MTG and DAPI, and representative images are shown. Scale bar, 100 μm. D, basal OCR was measured and shown. For statistical analysis, two-way analysis of variance and Bonferroni's post hoc tests were performed in A, and one-way analysis of variance plus Bonferroni's post hoc tests were carried out in D. All values are represented as means with error bars representing S.D. *, p < 0.05; **, p < 0.01; and ***, p < 0.001. n = 5 for each group.
Figure 6.
Figure 6.
Taurine-regulated PGC1α expression is AMPK signaling-dependent. A, C3H10T1/2 white adipocytes were treated with taurine at the indicated dose or with PBS as a control. After 24 h of treatment, cells were harvested for analyses. Cell lysates were subjected to Western blotting by using the indicated antibodies. B, fractionated and differentiated primary iWAT adipocytes were treated with taurine at a final concentration of 1 mm or with PBS as a control. After 24 h of treatment, cells were harvested for analyses. Cell lysates were subjected to Western blotting by using the indicated antibodies. C, mice were treated as indicated in Fig. 1. The tissue lysates of iWAT were subjected to Western blotting by using the indicated antibodies. D, C3H10T1/2 white adipocytes were transfected with the control siRNA (siNC) or two separate siRNAs (siAMPK1/2) against AMPKα1. 48 h post-transfection, cells were treated with taurine at a final concentration of 1 mm or with PBS as a control. After 24 h of treatment, cells were harvested for analyses. Cell lysates were subjected to Western blotting by using the indicated antibodies. E, cells were treated as in D, and OCR was measured. F, cells were treated as in D and then stained with MTG and DAPI. Representative images are shown. Scale bar, 100 μm. For statistical analysis, one-way analysis of variance plus Bonferroni's post hoc tests were carried out in E. All values are represented as means with error bars representing S.D. *, p < 0.05. n = 5 for each group.
Figure 7.
Figure 7.
Specific knockdown of PGC1α in iWAT blocks taurine-induced browning of iWAT. The 6-week-old C57BL6 male mice were fed a HFD for 14 weeks before being sacrificed for analyses. During the last 5 weeks of HFD feeding, mice were administered taurine intraperitoneally (150 mg/kg per mouse, once a day) or PBS as a control. During the last 4 weeks of HFD feeding, adenoviruses harboring the shRNA against LacZ (shLacZ) or shRNA against PGC1α (shPGC1α) were injected subcutaneously adjacent to iWAT on both sides of the mouse once a week. A, mRNA levels of the indicated genes in the indicated tissues were determined by using RT-qPCR. Data were normalized to PBS + shLacZ group. B, iWAT tissue lysates were then subjected to Western blotting by using the indicated antibodies. β-Actin serves as an internal control. C, IHC for UCP1 protein (brown stain) in iWAT sections of the mice. Scale bar, 50 μm. D, representative H&E staining images of iWAT of the mice. Scale bar, 20 μm. Arrows indicate the adipocytes with multilocular morphology. E, mtDNA copy number of iWAT. Data were normalized to the PBS + shLacZ group. F, OCR of the iWAT. For statistical analysis, one-way analysis of variance plus Bonferroni's post hoc tests were carried out in E and F, and two-way analysis of variance plus Bonferroni's post hoc tests were carried out in A. **, p < 0.01; ***, p < 0.001. All values are represented as means with error bars representing S.D. n = 5 for each group.
Figure 8.
Figure 8.
Anti-obesity effect of taurine was partially impaired upon the specific knockdown of PGC1α in iWAT. The 6-week-old C57BL6 male mice were fed a HFD for 14 weeks before being sacrificed for analyses. During the last 5 weeks of HFD feeding, mice were administered taurine intraperitoneally (150 mg/kg per mouse, once a day) or PBS as a control. During the last 4 weeks of HFD feeding, adenoviruses harboring the shRNA against LacZ (shLacZ) or shRNA against PGC1α (shPGC1α) were injected subcutaneously adjacent to iWAT on both sides of the mice once a week. A, rectal temperature of the mice was recorded at the indicated time points after cold exposure (4 °C). B, body weights (BW) of the mice before taurine treatment and 5 weeks after taurine treatment. C, fat mass levels of the mice after 5 weeks of taurine treatment. D, plasma FFA levels of the mice after overnight fasting. E and F, glucose concentrations during an i.p. glucose tolerance test (E) or an insulin tolerance test (F). For statistical analysis, one-way analysis of variance plus Bonferroni's post hoc tests were carried out in C and D, and two-way analysis of variance plus Bonferroni's post hoc tests were carried out in A, B, E, and F. For the statistical analysis in E and F, data were compared between taurine + shLacZ group and taurine + shPGC1α group. *, p < 0.05. All values are represented as means with error bars representing S.D. n = 5 for each group.
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References

    1. Smith K. B., and Smith M. S. (2016) Obesity statistics. Prim. Care 43, 121–135 10.1016/j.pop.2015.10.001 - DOI - PubMed
    1. Zobel E. H., Hansen T. W., Rossing P., and von Scholten B. J. (2016) Global changes in food supply and the obesity epidemic. Curr. Obes. Rep. 5, 449–455 10.1007/s13679-016-0233-8 - DOI - PubMed
    1. Bhupathiraju S. N., and Hu F. B. (2016) Epidemiology of obesity and diabetes and their cardiovascular complications. Circ. Res. 118, 1723–1735 10.1161/CIRCRESAHA.115.306825 - DOI - PMC - PubMed
    1. Grundy S. M. (2016) Overnutrition, ectopic lipid and the metabolic syndrome. J. Investig. Med. 64, 1082–1086 10.1136/jim-2016-000155 - DOI - PubMed
    1. Tseng Y. H., Cypess A. M., and Kahn C. R. (2010) Cellular bioenergetics as a target for obesity therapy. Nat. Rev. Drug Discov. 9, 465–482 10.1038/nrd3138 - DOI - PMC - PubMed

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