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Glucose enhances catecholamine-stimulated lipolysis via increased glycerol-3-phosphate synthesis in 3T3-L1 adipocytes and rat adipose tissue

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Abstract

Background

During lipolysis, triglyceride (TG) are hydrolyzed into a glycerol and fatty acids in adipocyte. A significant portion of the fatty acids are re-esterificated into TG, and this is a critical step in promoting lipolysis. Although glycerol-3-phosphate (G3P) is required for triglyceride synthesis in mammalian cell, the substrate for G3P synthesis during active lipolysis is not known. A recent study showed that the inhibition of glucose uptake reduces catecholamine-stimulated lipolysis, suggesting that glucose availability is important in lipolysis in adipocytes. We hypothesized that glucose might play an essential role in generating G3P and thereby promoting catecholamine-stimulated lipolysis in adipocytes. Therefore, we determined the effect of glucose availability on catecholamine-stimulated lipolysis in 3T3-L1 adipocytes and rat adipose tissue.

Methods and Results

3T3-L1 adipocytes and rat epididymal fat pads were cultured in a medium with/without glucose during stimulation by isoproterenol. Glycerol release was higher when adipocytes were cultured in a glucose-containing medium than that in a medium without glucose. Measurement of glucose uptake during catecholamine-stimulated lipolysis showed a slight, but significant increase in glucose uptake. We also compared glucose metabolism-related protein, such as glucose transporter 4, hexokinase, glycerol-3-phosphate dehydrogenase and lipase contents between fat tissues that play a critical role in active lipolysis. Epididymal fat exhibited higher lipolytic activity than inguinal fat because of higher lipase and glucose metabolism-related protein contents.

Conclusion

We demonstrated that catecholamine-stimulated lipolysis is enhanced in the presence of glucose, and suggests that glucose is one of the primary substrates for G3P in adipocytes during active lipolysis.

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Acknowledgements

This work was supported by Grant-in-Aid for Scientific Research (C) (20K11364 to HK, 19K11553 to NN) from the Japan Society for the Promotion of Science (JSPS). We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by Grant-in-Aid for Scientific Research (C) (20K11364 to HK, 19K11553 to NN) from the Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Laboratory of Exercise Nutrition, Department of Nutrition, University of Shiga Prefecture, 2500 Hassaka-cho, Hikone, Shiga, 522-8533, Japan

    Nodoka Takeuchi, Kazuhiko Higashida & Naoya Nakai

  2. Exercise Biology Research Center, China Institute of Sport Science, Beijing, China

    Xi Li

Authors
  1. Nodoka Takeuchi
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  2. Kazuhiko Higashida
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  3. Xi Li
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  4. Naoya Nakai
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Contributions

NT, KH, XL, and NN conceived and designed research; NT, KH, XL, and NN performed experiments; NT, KH, XL, and NN analyzed data; NT, KH, XL, and NN interpreted results of experiments; NT and KH prepared figures; NT and KH drafted manuscript; NT, KH, XL, and NN edited and revised manuscript; NT, KH, XL, and NN approved final version of manuscript.

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Correspondence to Kazuhiko Higashida.

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Animal Experimental Committee of University of Shiga Prefecture approved this experimental protocol (Ref #30-10).

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11033_2021_6617_MOESM1_ESM.tif

Supplementary file1—Supplementary Figure 1 Effect of glucose on lipolysis in basal and catecholamine-stimulated state. 3T3-L1 adipocytes (A) were cultured in DMEM with 1 μM of isoproterenol (Iso) with/without 5.5 mM glucose for 4 h. Rat fat pads were cultured in DMEM (B) or KRBH (C) with 1 μM of Iso with/without 5.5 mM glucose for 2 h. The concentration of FFA in medium during basal and Iso-stimulated lipolysis were measured. All data are presented as means ± SEM. n = 3-5. Two-way ANOVA was performed. *p <0.05 vs. same treatment in basal group. #p <0.05 vs. Man group. Man, Mannitol; Glu, Glucose; FFA, free fatty acids. (TIF 11315 kb)

11033_2021_6617_MOESM2_ESM.tif

Supplementary file2—Supplementary Figure 2 Effect of glucose concentration on glycerol release during catecholamine-stimulated lipolysis. 3T3-L1 adipocytes were stimulated by 1 μM of isoproterenol in the DMEM containing 0, 2.3, 5.5 or 11 mM glucose for 4 h. All data are presented as means ± SEM. n = 4. One-way ANOVA was performed. * p <0.05, ** P<0.01 vs. 0 mM glucose, respectively. (TIF 14422 kb)

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Takeuchi, N., Higashida, K., Li, X. et al. Glucose enhances catecholamine-stimulated lipolysis via increased glycerol-3-phosphate synthesis in 3T3-L1 adipocytes and rat adipose tissue. Mol Biol Rep 48, 6269–6276 (2021). https://doi.org/10.1007/s11033-021-06617-1

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