Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)

Ho Gyun Lee; Il Hyeon Jung; Byong Seo Park; Hye Rim Yang; Kwang Kon Kim; Thai Hien Tu; Jung-Yong Yeh; Sewon Lee; Sunggu Yang; Byung Ju Lee; Jae Geun Kim; Il Seong Nam-Goong

doi:10.4093/dmj.2022.0458

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Response Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95): Ho Gyun Lee¹, Il Hyeon Jung¹, Byong Seo Park¹, Hye Rim Yang¹, Kwang Kon Kim², Thai Hien Tu¹, Jung-Yong Yeh¹, Sewon Lee³, Sunggu Yang⁴, Byung Ju Lee², Jae Geun Kim^1,5, Il Seong Nam-Goong⁶; Diabetes & Metabolism Journal 2024;48(1):159-160.
DOI: https://doi.org/10.4093/dmj.2022.0458
Published online: January 29, 2024

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¹Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, Korea

²Department of Biological Science, University of Ulsan, Ulsan, Korea

³Division of Sport Science, College of Arts & Physical Education, Incheon National University, Incheon, Korea

⁴Department of Nano-Bioengineering, College of Life Science and Technology, Incheon National University, Incheon, Korea

⁵Research Center of Brain-Machine Interface, Incheon National University, Incheon, Korea

⁶Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

Corresponding authors: Jae Geun Kim

Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Korea E-mail: jgkim@inu.ac.kr

Il Seong Nam-Goong

Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan 44033, Korea E-mail: paul@uuh.ulsan.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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See the letter "Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)" on page 157.

We greatly appreciated the insightful comments on our recently published paper, “Altered metabolic phenotypes and hypothalamic neuronal activity triggered by sodium-glucose cotransporter 2 inhibition [1].”

First, we would like to address the concerns raised. Specifically, we acknowledge the absence of comprehensive metabolic characterization, especially in mice subjected to a high-fat diet. You correctly pointed out the importance of metabolic traits such as glycemic status and insulin resistance when studying the effects of drugs like sodium-glucose cotransporter 2 (SGLT2) inhibitors [2]. We agree that providing a more detailed metabolic profile of the mice, including parameters like glucose metabolism and insulin sensitivity, would add valuable context to our findings. While these specific results were not included in the manuscript, we did confirm a reduction in plasma glucose level in mice treated with dapagliflozin.

In our future research, we will consider incorporating these variables to gain a more comprehensive understanding of the metabolic effects of SGLT2 inhibitors under various dietary conditions.

Second, we understand the concerns raised about whether the impact of dapagliflozin on appetite, energy expenditure, and body weight is a direct result or an indirect effect. We acknowledge the complexity of drug interactions, including both direct and indirect influences, which can affect outcomes in clinical and preclinical studies. While investigating the precise mechanisms by which dapagliflozin affects the central nervous system may not be the primary clinical objective, such research can contribute to our understanding of the drug’s actions and its potential optimization in combination with other therapies. For instance, the hyperphagic effect of SGLT-2 inhibitor treatment may be beneficial in conjunction with glucagon-like peptide-1 receptor agonist administration, which leads to a reduction in appetite, for the treatment of obesity [3,4]. In our future studies, we intend to thoroughly examine these mechanisms, as you suggested, to better inform treatment strategies for individual patients.

In conclusion, we sincerely appreciate the constructive feedback. We recognize the importance of ongoing research in the field of precision medicine. Understanding how antidiabetic medications like SGLT2 inhibitors impact various aspects of metabolism and how they can be optimized for different patient populations is critical. We will certainly take these valuable comments into consideration as we continue our research on this topic.

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CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

REFERENCES

1. Lee HG, Jung IH, Park BS, Yang HR, Kim KK, Tu TH, et al. Altered metabolic phenotypes and hypothalamic neuronal activity triggered by sodium-glucose cotransporter 2 inhibition. Diabetes Metab J 2023;47:784-95.Article PubMed PMC PDF
2. Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab 2016;18:783-94.Article PubMed
3. Brown E, Wilding JPH, Barber TM, Alam U, Cuthbertson DJ. Weight loss variability with SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes mellitus and obesity: mechanistic possibilities. Obes Rev 2019;20:816-28.Article PubMed PDF
4. Lu K, Chen X, Yan J, Li X, Huang C, Wan Q, et al. The effect of feeding behavior on hypothalamus in obese type 2 diabetic rats with glucagon-like peptide-1 receptor agonist intervention. Obes Facts 2018;11:181-94.Article PubMed PMC PDF

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Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)

Diabetes Metab J. 2024;48(1):159-160. Published online January 29, 2024

DOI: https://doi.org/10.4093/dmj.2022.0458

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Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)

About this article

Lee HG, Jung IH, Park BS, Yang HR, Kim KK, Tu TH, Yeh JY, Lee S, Yang S, Lee BJ, Kim JG, Nam-Goong IS. Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95). Diabetes Metab J. 2024;48(1):159-160.

DOI: https://doi.org/10.4093/dmj.2022.0458.

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