Diet-induced obese mice retain endogenous leptin action

Area of Science:

• Physiology
• Endocrinology
• Obesity Research

Background:

• Obesity is linked to high leptin levels (hyperleptinemia) and reduced sensitivity to leptin.
• Leptin resistance is a proposed mechanism contributing to obesity development and maintenance.
• Understanding endogenous leptin activity in obesity is crucial for therapeutic strategies.

Purpose of the Study:

• To directly assess the activity of endogenous leptin in obese mice.
• To investigate whether leptin resistance impacts diet-induced obesity (DIO) persistence.

Main Methods:

• Administration of a leptin receptor antagonist to lean and obese mice.
• Assessment of feeding behavior and body weight (BW) changes.
• Measurement of hypothalamic suppressor of cytokine signaling 3 (Socs3) expression.

Main Results:

• Leptin receptor antagonist increased feeding and BW in lean mice.
• Antagonist had no effect on feeding or BW in genetically obese mouse models.
• Antagonist increased feeding and BW in diet-induced obese (DIO) mice, similar to lean mice.
• DIO mice showed decreased hypothalamic Socs3 expression after antagonist treatment.

Conclusions:

• Diet-induced obese mice maintain functional leptin signaling for feeding suppression.
• Resistance to endogenous leptin does not appear to drive the persistence of diet-induced obesity in mice.
• These findings challenge the prevailing view of leptin resistance as a primary driver of DIO persistence.