Nicotine Alters Food–Cue Reactivity via Networks Extending From the Hypothalamus

Abstract

Obesity and smoking constitute two of the main causes of preventable deaths in the developed countries today. Many smokers motivate consumption as a means to control their body weight because smoking cessation increases the risk to gain weight. Although it is well established that nicotine reduces feeding in animals and that smoking is associated with reduced body weight in quasi-experimental studies of humans, acute nicotine effects are mixed and little is known about the brain networks supporting these effects. Thus, we investigated 26 normal-weighted never-smokers who received either nicotine (2 mg) or placebo gums following a double-blinded randomized cross-over design. We used functional magnetic resonance imaging (fMRI) to investigate reactivity to palatable food cues after both overnight fasting and following a standardized caloric intake (75 g oral glucose tolerance test (OGTT)). Participants viewed food or low-level control pictures in a block design and rated their current appetite after each block. Nicotine had a small-to mediumsized effect on subjective appetite and significantly altered food-cue reactivity in a region sensitive to caloric intake that extended from the right hypothalamus to the basal ganglia. During placebo sessions, the OGTT reduced functional coupling of this region with a 'salience network' (ie, amygdala, ventromedial prefrontal cortex) in processing of food pictures. Furthermore, nicotine reduced coupling with the nucleus accumbens and the OGTT reduced coupling with an 'interoceptive network' (ie, insula, operculum) instead. We conclude that locally restricted acute effects of nicotine in the hypothalamic area have profound effects on food-processing networks.

Blunted striatal responses to favorite-food cues in smokers

“…Neural responses to food cues differ by body mass index (BMI; Martin et al, 2010, Stice et al, 2008, Stoeckel et al, 2008), with greater responsivity of brain-reward regions and subjective food craving associated with higher BMI (Pelchat et al, 2004, Simansky, 2005, Stice et al, 2008). Nicotine has been found to decrease appetite and neural differences between responses to food and control pictures in lean, never-smokers (Kroemer et al, 2013). …”

Nicotine enhances modulation of food‐cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex

“…In general, administration of nicotine had a small‐ to medium‐sized attenuating effect on subjective appetite ratings during fasting but not after caloric load (for details, see Kroemer et al . ). However, there were no significant differences in initial subjective appetite ratings (i.e.…”

“…In contrast, activation increased in the middle temporal gyrus (BA22; −50/−44/−4; t max = 3.98), middle frontal gyrus (BA6; 34/12/50; t max = 3.88) and the culmen (−38/−56/−36; t max = 3.88; for main effects of nicotine, see Kroemer et al . ).…”

“…We reassessed the psychophysiological interaction (PPI) statistics described in Kroemer et al . (; for details, see Supporting Information) that used a right hypothalamic cluster (10/0/−4) as seed region and extracted the PPI estimates of functional coupling to vmPFC. Regression analyses using ghrelin and leptin levels as predictors indicated that during placebo sessions, the functional coupling of hypothalamus and vmPFC was positively correlated with ghrelin (β Pla = .35) but negatively during nicotine sessions (β Nic = −.26), and this was significantly different as indicated by the interaction term Ghrelin × Nicotine Administration in a multi‐level regression analysis ( t = −2.68, P = .01; see Supporting Information).…”

“…Recently, we have shown that nicotine administration in humans affects hypothalamic signaling in response to food pictures by decoupling the hedonic‐hunger network from homeostatic hunger feedback (Kroemer et al . ). Taken together, these results suggest that endogenous acetylcholine or nicotine may mediate the effect of leptin in this circuit (Meister et al .…”