Loss of transketolase promotes the anti-diabetic role of brown adipose tissues

in Journal of Endocrinology
Authors:
Yingning Ji Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Wei Liu Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China

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Yemin Zhu Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Yakui Li Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Ying Lu Department of Biochemistry and Molecular Biology of School of Basic Medical College of Fudan University, Shanghai, China

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Qi Liu Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Lingfeng Tong Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Lei Hu Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Nannan Xu Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Zhangbing Chen Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Na Tian Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China

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Lifang Wu Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Lian Zhu Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Shuang Tang Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China

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Ping Zhang Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Xuemei Tong Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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https://orcid.org/0000-0002-2127-2019

Correspondence should be addressed to X Tong or P Zhang: xuemeitong@shsmu.edu.cn or ssmuzp@139.com
DOI:
https://doi.org/10.1530/JOE-22-0047
Volume/Issue:
Volume 256: Issue 3
Article Type:
Research Article
Article ID:
e220047
Online Publication Date:
24 Jan 2023
Copyright:
© Society for Endocrinology 2023
Restricted access
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Transketolase (TKT), an enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP), bi-directionally regulates the carbon flux between the PPP and glycolysis. Loss of TKT in adipose tissues decreased glycolysis and increased lipolysis and uncoupling protein-1 (UCP1) expression, protecting mice from high-fat diet-induced obesity. However, the role of TKT in brown adipose tissue (BAT)-dependent glucose homeostasis under normal chow diet remains to be elucidated. We found that TKT ablation increased levels of glucose transporter 4 (GLUT4), promoting glucose uptake and glycogen accumulation in BAT. Using the streptozotocin (STZ)-induced diabetic mouse model, we discovered that enhanced glucose uptake due to TKT deficiency in BAT contributed to decreasing blood glucose and weight loss, protecting mice from STZ-induced diabetes. Mechanistically, TKT deficiency decreased the level of thioredoxin-interacting protein, a known inhibitor for GLUT4, by decreasing NADPH and glutathione levels and inducing oxidative stress in BAT. Therefore, our data reveal a new role of TKT in regulating the anti-diabetic function of BAT as well as glucose homeostasis.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2023
Article ID:
e220047
Article Type:
Research Article
Received Date:
16 Nov 2022
Accepted Date:
30 Nov 2022
Print Publication Date:
01 Mar 2023
Online Publication Date:
24 Jan 2023
Keywords:
TKT; BAT; glucose uptake; TXNIP; NADPH

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