Brain Insulin's Appetite-Suppressing Effects Show Inconsistent Results in Mice

Insulin, a hormone primarily known for regulating blood glucose, also plays a crucial role in the central nervous system, particularly in appetite control and energy homeostasis. When administered directly into the brain via intracerebroventricular (ICV) injection, insulin is often observed to reduce food intake, a phenomenon known as hypophagia. However, the consistency and reliability of this central effect have been debated across studies, and the precise factors contributing to variability in insulin's hypophagic action in the brain remain poorly understood.

Across multiple independent experimental cohorts, the study revealed significant variability in the hypophagic response to ICV insulin, even under seemingly identical conditions. While some groups demonstrated a robust and statistically significant reduction in food intake, others showed no significant effect, or only a transient, non-sustained decrease. In cohorts where ICV insulin was effective, a 10.0 mU dose of insulin consistently reduced 24-hour food intake by an average of 25-30% compared to saline-treated controls (p<0.01). However, in other identically treated cohorts, the same 10.0 mU dose resulted in only a 5-10% reduction (p>0.05), or no statistically significant difference in food consumption. This inconsistency was observed despite stringent control over factors such as time of day, housing conditions, and mouse strain, suggesting complex, uncharacterized modulators of central insulin sensitivity.