Interleukin-4 inhibits the hypothalamic appetite control by modulating the insulin-AKT and JAK-STAT signaling in leptin mutant mice.
Environ Toxicol
; 39(7): 3980-3990, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38597583
ABSTRACT
Our previous research identified interleukin-4 (IL-4) as a key regulator of glucose/lipid metabolism, circulatory leptin levels, and insulin action, suggesting its potential as a therapeutic target for obesity and related complications. This study aimed to further elucidate the role of IL-4 in regulating hypothalamic appetite-controlling neuropeptides using leptin dysfunctional Leptin145E/145E mice as the experimental model. IL-4 significantly reduces body weight, food intake, and serum glucose levels. Our data demonstrated that IL-4 exhibits multiple functions in regulating hypothalamic appetite control, including downregulating orexigenic agouti-related peptide and neuropeptide Y levels, promoting expression of anorexigenic proopiomelanocortin, alleviating microenvironmental hypothalamic inflammation, enhancing leptin and insulin pathway, and attenuating insulin resistance. Furthermore, IL-4 promotes uncoupling protein 1 expression of white adipose tissue (WAT), suggesting its role in triggering WAT-beige switch. In summary, this study uncovers novel function of IL-4 in mediating food-intake behaviors and metabolic efficiency by regulating hypothalamic appetite-control and WAT browning activities. These findings support the therapeutic potential of targeting hypothalamic inflammation and reducing adiposity through IL-4 intervention for tackling the pandemic increasing prevalence of obesity and associated metabolic disorders.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Transducción de Señal
/
Interleucina-4
/
Leptina
/
Hipotálamo
/
Insulina
Límite:
Animals
Idioma:
En
Revista:
Environ Toxicol
/
Environ. toxicol
/
Environmental toxicology
Asunto de la revista:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Taiwán