Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men

Abstract

Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.

The role of oxytocin in regulation of appetitive behaviour, body weight and glucose homeostasis

“…The anorexigenic properties of OXT appear to be mediated by homeostatic and reward‐related neural pathways . Studies in humans support these mechanisms, and also indicate that OXT may act via modulating impulse control circuitry . Although studies in animal models show that acute or chronic administration of OXT increases energy expenditure, single dose i.n.…”

“…Importantly OXT reduces food intake in fasted and fed states with preferential effects in reducing sweet, fatty and salty foods, suggesting effects on both homeostatic and hedonic eating. Mechanistic studies using functional magnetic resonance imaging (fMRI) have confirmed that OXT modulates homeostatic (eg, hypothalamus) and hedonic (eg, ventral tegmental area, orbitofrontal cortex, insula) neurocircuitry in response to food images. In addition, fMRI studies have shown that OXT increases activation of brain regions responsible for self‐control (eg, anterior cingulate cortex, prefrontal cortex, supplementary motor area) .…”

“…Mechanistic studies using functional magnetic resonance imaging (fMRI) have confirmed that OXT modulates homeostatic (eg, hypothalamus) and hedonic (eg, ventral tegmental area, orbitofrontal cortex, insula) neurocircuitry in response to food images. In addition, fMRI studies have shown that OXT increases activation of brain regions responsible for self‐control (eg, anterior cingulate cortex, prefrontal cortex, supplementary motor area) . Therefore, OXT may reduce caloric intake in humans via effects on multiple neurobiological pathways, including homeostatic, hedonic and impulse control circuitry.…”

Oxytocin in metabolic homeostasis: implications for obesity and diabetes management

“…Whole-brain analysis by functional magnetic resonance imaging also showed reduced activation in reward-related food motivation brain regions in subjects treated with oxytocin. In addition, oxytocin administration was associated with reduced activity in the hypothalamus, a region central to homeostatic control of feeding, in male subjects across the weight spectrum (118,119). Oxytocin also increased functional magnetic resonance imaging activation in brain regions involved in cognitive control, a process that enables individuals to suppress behavioural impulses to achieve a desired outcome, e.g.…”

Unravelling the role and mechanism of adipokine and gastrointestinal signals in animal models in the nonhomeostatic control of energy homeostasis: Implications for binge eating disorder

“…In fact, intranasal oxytocin treatment in human has been widely studied (Sippel et al, 2017), mainly in the context of eating disorders (Kim, Eom, Leppanen, Leslie, & Treasure, 2018;Kim, Kim, Cardi, et al, 2014;Kim, Kim, Park, Pyo, & Treasure, 2014;Leppanen et al, 2017). This intranasal treatment suppresses hypothalamic activation in response to visual food cues (van der Klaauw et al, 2017) and causes bilateral VTA hypoactivation to high-calorie food stimuli and also in additional hedonic pathways (Plessow et al, 2018). Furthermore, intranasal oxytocin appears to limit food intake in humans by enhancing the activity of fronto-cortical brain areas that establish cognitive control processes, thereby overriding the hedonic drive to eat (Spetter et al, 2018).…”