Obese men are resistant to the weight reducing effects of intranasal insulin

Objectives: Circulating insulin is considered a major adiposity signal since after crossing the blood-brain barrier, it acts in the central nervous system to reduce food intake and body weight. After intranasal administration, insulin enters the cerebrospinal fluid compartment and alters brain functions in the absence of substantial absorption into the blood stream. In a recent study in normal weight men, 8 weeks of intranasal insulin administration induced loss of body weight and body fat and improved declarative memory. The present experiments aimed to generalize these findings to obese patients.

Methods: Insulin and placebo, respectively, were intranasally administered 4 times a day (amounting to 160 IU/d) over a period of 8 weeks to two groups of 13 obese men each (body mass index, mean±SEM: insulin, 32.10±1.24; placebo, 31.85±0.89kg/m²).

Results: Contrasting with the catabolic effects found in normal weight men, in the obese subjects neither 4 nor 8 weeks of insulin treatment induced any significant reduction of body weight and body fat. However, in accordance with the cognitive effects observed in normal weight men, 8 weeks of insulin administration improved declarative memory performance in obese subjects.

Conclusion: Our results indicate that increasing the availability of central nervous insulin in obese men enhances cognitive brain functions but fails to affect the hypothalamic networks involved in the regulation of body weight. In line with findings in animals, this outcome suggests that obesity in humans is associated with decreased central nervous sensitivity to the adiposity signal insulin. In conjunction with impaired blood-to-brain transport of insulin, this effect may contribute to the persistence of obesity in spite of elevated levels of circulating insulin.