Olanzapine-depot administration induces time-dependent changes in adipose tissue endocrine function in rats

Area of Science:

• Endocrinology
• Metabolic Syndrome
• Pharmacology

Background:

• Metabolic adverse effects of atypical antipsychotics (AAP) increase cardiovascular risks in schizophrenia patients.
• Mechanisms of AAP-induced metabolic dysfunction are not fully understood.
• Adipose tissue metabolism and neurohormonal regulation are emerging areas of interest.

Purpose of the Study:

• To investigate the time-dependent effects of olanzapine depot on energy homeostasis and related hormones.
• To assess olanzapine's impact on glucose and lipid metabolism in female Sprague-Dawley rats.
• To evaluate changes in gastrointestinal and adipose tissue-derived hormones.

Main Methods:

• Olanzapine depot administered to female Sprague-Dawley rats for 8 weeks.
• Markers assayed at multiple time-points: day 8, 15, 29, 43, and 57.
• Evaluation of weight, adiposity, lipid profile, and serum hormone levels (leptin, ghrelin, FGF-21) and inflammatory markers.

Main Results:

• Olanzapine induced weight gain and increased adiposity without hyperphagia.
• Early alterations in lipid profile included increased triglycerides.
• A biphasic, time-dependent effect on leptin was observed; ghrelin, FGF-21, and inflammatory markers remained unchanged.

Conclusions:

• Early alterations in adipose tissue endocrine function are implicated in antipsychotic metabolic adverse effects.
• Olanzapine's chronic administration impacts energy balance regulation.
• Further research into adipose tissue's role is crucial for understanding and mitigating AAP side effects.