Lipocalin 2 Does Not Play A Role in Celastrol-Mediated Reduction in Food Intake and Body Weight

Area of Science:

• Metabolism and Endocrinology
• Obesity Research
• Pharmacology

Background:

• Celastrol demonstrates significant anti-obesity effects by enhancing leptin sensitivity.
• The specific genes and molecular pathways involved in celastrol's action remain incompletely elucidated.
• Lipocalin-2 (LCN2) has been implicated as a potential anorexigenic and anti-obesity factor.

Purpose of the Study:

• To identify genes and pathways mediating celastrol's leptin-sensitizing and anti-obesity effects.
• To investigate the role of lipocalin-2 (LCN2) in diet-induced obesity and celastrol's therapeutic efficacy.

Main Methods:

• Comparative analysis of hypothalamic transcriptomes in diet-induced obese (DIO) mice treated with celastrol versus vehicle.
• Measurement of LCN2 protein levels across various tissues and plasma following celastrol administration.
• Assessment of obesity development and metabolic parameters in LCN2-deficient DIO mice with and without celastrol treatment.

Main Results:

• Lipocalin-2 (LCN2) was identified as the most significantly upregulated gene in the hypothalamus by celastrol in DIO mice.
• Celastrol treatment led to increased LCN2 protein levels in the hypothalamus, liver, adipose tissue, muscle, bone marrow, and plasma.
• Genetic deficiency of LCN2 did not impede the development of diet-induced obesity or affect celastrol's efficacy in promoting weight loss and improving metabolic dyshomeostasis.

Conclusions:

• Lipocalin-2 (LCN2) is upregulated by celastrol but is dispensable for celastrol's anti-obesity effects in diet-induced obese mice.
• The mechanism of celastrol's therapeutic action in obesity does not rely on LCN2.
• Further research is needed to fully understand the molecular underpinnings of celastrol-induced leptin sensitization and weight management.