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Interleukin-4 inhibits the hypothalamic appetite control by modulating the insulin-AKT and JAK-STAT signaling in

Shu-Mei Chen1, Chiao-Wan Hsiao2, Yen-Ju Chen3

  • 1Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.

Environmental Toxicology
|April 10, 2024
PubMed

Insights

Interleukin-4 (IL-4) reduces body weight and food intake by regulating appetite-controlling neuropeptides in the hypothalamus. This cytokine also enhances metabolic efficiency and promotes white adipose tissue browning, offering therapeutic potential for obesity.

Area of Science:

  • Immunology
  • Metabolic Research
  • Neuroendocrinology

Background:

  • Previous research identified Interleukin-4 (IL-4) as a key regulator of glucose/lipid metabolism, leptin levels, and insulin action.
  • IL-4's potential as a therapeutic target for obesity and related complications was suggested.
  • The role of IL-4 in regulating hypothalamic appetite-controlling neuropeptides remained to be elucidated.

Purpose of the Study:

  • To investigate the role of IL-4 in regulating hypothalamic appetite-controlling neuropeptides.
  • To utilize leptin dysfunctional Leptin145E/145E mice as an experimental model.
  • To further understand IL-4's functions in appetite control and metabolic regulation.

Main Methods:

  • Experimental model: Leptin dysfunctional Leptin145E/145E mice.
  • Administration of Interleukin-4 (IL-4).
  • Assessment of body weight, food intake, serum glucose, hypothalamic neuropeptide expression, leptin/insulin signaling, insulin resistance, and white adipose tissue (WAT) browning markers (uncoupling protein 1).

Main Results:

  • IL-4 significantly reduced body weight, food intake, and serum glucose levels.
  • IL-4 downregulated orexigenic neuropeptides (agouti-related peptide, neuropeptide Y) and upregulated anorexigenic proopiomelanocortin.
  • IL-4 alleviated hypothalamic inflammation, enhanced leptin/insulin signaling, attenuated insulin resistance, and promoted WAT browning.

Conclusions:

  • IL-4 exhibits multiple functions in regulating hypothalamic appetite control and metabolic efficiency.
  • IL-4 mediates food intake behaviors and promotes WAT browning.
  • Targeting hypothalamic inflammation and adiposity via IL-4 intervention holds therapeutic potential for obesity and metabolic disorders.
Keywords:
IL‐4appetitehypothalamusinsulinleptinleptin145E/145E obese miceobesityorexigenic and anorexigenic neuropeptides

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