Basolateral Amygdala Response to Food Cues in the Absence of Hunger Is Associated with Weight Gain Susceptibility

Abstract

In rodents, food-predictive cues elicit eating in the absence of hunger (Weingarten, 1983). This behavior is disrupted by the disconnection of amygdala pathways to the lateral hypothalamus (Petrovich et al., 2002). Whether this circuit contributes to long-term weight gain is unknown. Using fMRI in 32 healthy individuals, we demonstrate here that the amygdala response to the taste of a milkshake when sated but not hungry positively predicts weight change. This effect is independent of sex, initial BMI, and total circulating ghrelin levels, but it is only present in individuals who do not carry a copy of the A1 allele of the Taq1A polymorphism. In contrast, A1 allele carriers, who have decreased D2 receptor density (Blum et al., 1996), show a positive association between caudate response and weight change. Regardless of genotype, however, dynamic causal modeling supports unidirectional gustatory input from basolateral amygdala (BLA) to hypothalamus in sated subjects. This finding suggests that, as in rodents, external cues gain access to the homeostatic control circuits of the human hypothalamus via the amygdala. In contrast, during hunger, gustatory inputs enter the hypothalamus and drive bidirectional connectivity with the amygdala. These findings implicate the BLA-hypothalamic circuit in long-term weight change related to nonhomeostatic eating and provide compelling evidence that distinct brain mechanisms confer susceptibility to weight gain depending upon individual differences in dopamine signaling.

DRD2: Bridging the Genome and Ingestive Behavior

“…Data from longitudinal studies examining the impact of the Taq1A A1 RFLP on weight gain are consistent with the pharmacological data, revealing opposing associations between response to food in DA source or target regions and weight gain as a function of genotype [93, 95, 98] (Figure 1). More specifically, caudate response to anticipated milkshake receipt is negatively associated with weight gain in carriers, but positively associated in non-carriers [93, 95], whereas the opposite is true amygdala response to milkshake in a sated state [98].…”

“…First, dorsal striatal response to milkshake is associated with measures of impulsivity but not of food reward/reinforcement [97]. Second, a positive association between weight gain and dorsal striatal milkshake response in A1 carriers but not non-carriers was recently reported [98]. Critically, milkshake delivery in this study was unpredicted.…”

“…More specifically, caudate response to anticipated milkshake receipt is negatively associated with weight gain in carriers, but positively associated in non-carriers [93, 95], whereas the opposite is true amygdala response to milkshake in a sated state [98]. Whether these effects reflect cause or consequence of obesity is an open question.…”

The anterior medial temporal lobes: Their role in food intake and body weight regulation

“…Thus, the amygdala responds to food cues (e.g., [32,166]). Additionally, it has been shown that the amygdala's response to food cues are modulated by hunger [47,88,169] and its response in the absence of hunger could predict weight gain susceptibility [159].…”

Contextual factors associated with eating in the absence of hunger among adults with obesity

“…(1) While multiple genetic and environmental factors contribute to obesity, (2) modifiable lifestyle factors such as eating behaviors have been subject to considerable research given their relevance to prevention and treatment. (3) Disinhibited eating, characterized by a lack of healthy restraint over eating including eating in the absence of hunger (EAH), (4) may promote excess energy intake, (5) unhealthy weight gain, (6–8) and obesity. (9–11) Contrary to pediatric samples, (12) EAH in adults is underexplored, (5, 13–17) particularly in the natural environment.…”