Interleukin-4 improves metabolic abnormalities in leptin-deficient and high-fat diet mice

Shih Yi Lin, Ching Ping Yang, Ya Yu Wang, Chiao Wan Hsiao, Wen Ying Chen, Su Lan Liao, Yu Li Lo, Yih Hsin Chang, Chen Jee Hong, Chun Jung Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Obesity is a metabolic disorder that results from complex interactions between genetic predisposition and dietary factors. Interleukin-4 (IL-4), besides its role in immunity, has metabolic effects on insulin efficacy. We studied the effects of IL-4 on metabolic abnormalities in a mice model of obesity involving leptin deficiency and leptin resistance. Leptin-deficient 145E and leptin-resistant high-fat diet (HFD) mice showed lower levels of circulating IL-4. 145E and HFD mice showed a number of abnormalities: Obesity, hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, liver injury, and adiposity with concurrent inflammation, decreases in Akt, signal transducer and activator of transcription 3 (STAT3), and STAT6 phosphorylation in the hypothalamus, liver, and epididymal fat. Independent of leptin-deficient obesity and dietary obesity, a course of 8-week IL-4 supplementation improved obesity and impairment in Akt, STAT3, and STAT6 signaling. Amelioration of cytokine expression, despite variable extents, was closely linked with the actions of IL-4. Additionally, the browning of white adipocytes by IL-4 was found in epididymal white adipose tissues and 3T3-L1 preadipocytes. Chronic exercise, weight management, and probiotics are recommended to overweight patients and IL-4 signaling is associated with clinical improvement. Thus, IL-4 could be a metabolic regulator and antiobesity candidate for the treatment of obesity and its complications.

Original languageEnglish
Article number4451
Pages (from-to)1-19
Number of pages19
JournalInternational Journal Of Molecular Sciences
Issue number12
StatePublished - 2020


  • Adiposity
  • IL-4
  • Inflammation
  • Leptin
  • Obesity


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