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Updated: Jul 12, 2025

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy
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Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2

Ho Gyun Lee1, Il Hyeon Jung1, Byong Seo Park1

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

Diabetes & Metabolism Journal
|November 2, 2023
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors alter metabolism. This study reveals the hypothalamus plays a key role in these compensatory metabolic changes, influencing appetite regulation in mice treated with SGLT-2 inhibitors.

Area of Science:

  • Metabolic Phenotyping
  • Neuroendocrinology
  • Pharmacology

Background:

  • Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are established diabetes treatments.
  • SGLT-2 inhibitor therapy is linked to altered metabolic phenotypes.
  • The role of the hypothalamus in these adaptive metabolic changes remains unexplored.

Purpose of the Study:

  • To investigate the involvement of the hypothalamic circuit in compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.
  • To elucidate the neural mechanisms underlying metabolic adaptations to SGLT-2 inhibition.

Main Methods:

  • Mice were administered dapagliflozin, an SGLT-2 inhibitor, under standard or high-fat diet conditions.
  • Indirect calorimetry assessed food intake and energy expenditure.
  • Immunohistochemistry and quantitative real-time PCR analyzed hypothalamic neuronal activity and gene expression.

Main Results:

  • Dapagliflozin treatment led to increased food intake and decreased energy expenditure in mice.
  • Neuronal activity in appetite-regulating hypothalamic nuclei was altered.
  • Elevated agouti-related peptide neuron activity was observed in the paraventricular nucleus.

Conclusions:

  • The hypothalamus is functionally involved in the development of metabolic phenotypes associated with SGLT-2 inhibitor therapy.
  • These findings highlight the central role of the hypothalamus in mediating adaptive metabolic responses to SGLT-2 inhibition.
Keywords:
AppetiteDapagliflozinEnergy metabolismHypothalamusObesity

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