The effect of intranasal insulin on appetite and mood in women with and without obesity: an experimental medicine study

Abstract

Background/Objectives Intranasal (IN) administration of insulin decreases appetite in humans, but the underlying mechanisms are unclear, and it is unknown whether IN insulin affects the food intake of women with obesity. Subjects/Methods In a double-blind, placebo-controlled, crossover design, participants (35 lean women and 17 women with obesity) were randomized to receive 160 IU/1.6 mL of IN insulin or placebo in a counterbalanced order in the post prandial state. The effects of IN insulin on cookie intake, appetite, mood, food reward, cognition and neural activity were assessed. Results IN insulin in the post prandial state reduced cookie intake, appetite and food reward relative to placebo and these effects were more pronounced for women with obesity compared with lean women. IN insulin also improved mood in women with obesity. In both BMI groups, IN insulin increased neural activity in the insula when viewing food pictures. IN insulin did not affect cognitive function. Conclusions These results suggest that IN insulin decreases palatable food intake when satiated by reducing food reward and that women with obesity may be more sensitive to this effect than lean women. Further investigation of the therapeutic potential of IN insulin for weight management in women with obesity is warranted.

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

“…Administration of INI to healthy individuals resulted in an increase in CBF velocity in the inferior frontal gyrus, dorsal striatum, and insular cortex [ 287 ], as well as a decrease in CBF velocity in the hypothalamus and around the middle frontal gyrus [ 267 , 288 ]. Since these brain areas are involved in the regulation of feeding behavior and the implementation of the reward and reinforcement program, in healthy subjects, INI affects appetite, motivation to food intake, and taste preferences, which is consistent with clinical observations [ 49 , 267 , 289 , 290 ]. At the same time, the effect of INI on hunger, perception of food stimuli, and reward behavior in women and men differs significantly, indicating a modulating effect of gender factor on INI-induced feeding behavior [ 290 ].…”

“…It has also been shown that INI can improve memory in healthy subjects [ 42 , 43 , 44 ], which can be used to restore their cognitive abilities in case of overwork, psycho-emotional exhaustion, sleep restriction, and other physiological conditions leading to transient, reversible cognitive decline, and mood deterioration. Since numerous studies indicate the safety of INI, including its use at relatively high doses [ 28 , 29 , 34 , 45 , 46 , 47 , 48 ], it can be used not only in the treatment of overt pathology but also in the prevention of mild cognitive impairment to improve mood and to increase learning ability, resistance to stress, and prolonged physical activity [ 45 , 47 , 48 , 49 ]. These data indicate a pronounced neuroprotective effect of INI, its ability to increase the viability of neurons and glial cells, and restore the functional interaction between brain signaling systems, providing integration between different brain structures and improving the central regulation of physiological functions.…”

Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese

“…Nevertheless, in this exploratory research, we were able to analyze and compare brain insulin action of participants who were overweight or obese from previous studies without an exercise intervention. Moreover, sex-specific findings have been identified on brain insulin responsivity ( 20 , 21 , 63 ), which could not be investigated in the current study based on the limited sample size. The correlative nature of the findings prohibits us to clarify mechanisms of actions.…”

“…2, 10). These diverse central insulin responses largely depend on its action in the hypothalamus, amygdala, hippocampus, striatum and parts of the insula and prefrontal cortex (PFC) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Specifically, central insulin action curbs food intake, improves mood and memory function (for review, see ref.…”

Consolidating evidence on the role of insulin resistance in major depressive disorder

“…Reportedly, further studies by these researchers assessing the effect of semaglutide and pioglitazone in TRBD are underway. What is more, it has been reported that intranasal insulin vs. placebo increased positive affect, food reward and reduced snacking in women and that this effect was more pronounced in obese but not lean participants [32] ] assessed the effectiveness of 12-week aerobicresistance training program on the metabolic parameters, BDNF and severity of depression in TMD2. Initial BDI indicated that both control and experimental groups showed severe levels of depression.…”