In vivo Protein Interference: Oral Administration of Recombinant Yeast-Mediated Partial Leptin Reduction for Obesity...

Area of Science:

• Metabolic diseases
• Obesity research
• Immunology

Background:

• Obesity and related diseases are significant global health concerns.
• Leptin, encoded by the obesity gene (ob), plays a crucial role in obesity development.
• The "Less Is More" model suggests partial leptin reduction enhances leptin sensitization for obesity control.

Purpose of the Study:

• To introduce and validate a novel protein knockdown strategy, in vivo protein interference (iPRTi), for partial leptin reduction.
• To assess the efficacy of iPRTi using oral administration of ob recombinant yeast in managing obesity and leptin resistance.

Main Methods:

• Induction of specific immune responses against leptin via oral administration of ob recombinant yeast.
• Observation of leptin resistance in diet-induced obese mice.
• Administration of ob recombinant yeast to obese mice to evaluate its effects on circulating leptin, body weight, and metabolic parameters.

Main Results:

• Oral administration of ob recombinant yeast successfully induced an immune response against leptin.
• Leptin resistance was observed in diet-induced obese mice.
• Treatment with ob recombinant yeast led to decreased circulating leptin, reduced body weight gain, and improved triglyceride and total cholesterol levels.

Conclusions:

• The in vivo protein interference (iPRTi) strategy demonstrates potential for partial leptin reduction.
• Oral administration of ob recombinant yeast is effective in controlling obesity and leptin resistance in a mouse model.
• This study presents a novel therapeutic strategy using recombinant yeast for individuals with obesity and leptin resistance.