Distinct Modulatory Effects of Satiety and Sibutramine on Brain Responses to Food Images in Humans: A Double Dissociation across Hypothalamus, Amygdala, and Ventral Striatum

Fletcher, Paul C.; Napolitano, A; Skeggs, Andrew; Miller, Stephan; Delafont, Bruno; Cambridge, Victoria C.; Wit, Sanne de; Nathan, Pradeep J.; Brooke, Allison C.; O’Rahilly, Stephen; Farooqi, I. Sadaf; Bullmore, Edward T.

doi:10.1523/jneurosci.3323-10.2010

Cited by 69 publications

(65 citation statements)

References 47 publications

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“…Saliva samples were obtained from the subjects using Oragene Discover collection kits and DNA extraction was performed as directed by the manufacturer (DNA Genotek). TaqIA A1 allele status was determined by amplifying a 304 bp region with PCR using forward (5Ј-CCCTTCCTGAGTGTCATCA-3Ј) and reverse (5Ј-CGGCTGGCCAA GTTGTCT-3Ј) primers as described by Epstein et al (2007). The products of the amplification were digested overnight with the restriction enzyme Taq␣I.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, these responses are heightened in obesity (Holsen et al, 2006;Stoeckel et al, 2008), predict subsequent high-fat food consumption (Mehta et al, 2012), and are inhibited by the appetite suppressants sibutramine and GSK1521498, a -opioid receptor antagonist (Fletcher et al, 2010;Rabiner et al, 2011). These findings suggest that individual differences in amygdala response to food cues might be associated with a vulnerability to overeating in an environment laden with food cues.…”

Section: Introductionmentioning

confidence: 93%

“…The TaqIA polymorphism lies on the ANKK1 gene downstream of the dopamine receptor D2 (DRD2) gene (Fossella et al, 2006). A1ϩ individuals have reduced central DRD2 availability (Thompson et al, 1997;Pohjalainen et al, 1998) and an increased incidence of addictive behaviors such as substance use, overeating, and obesity (Comings et al, 1993;Noble et al, 1994;Blum et al, 1996;Jenkinson et al, 2000;Klein et al, 2007;Esposito-Smythers et al, 2009). TaqIA also moderates the relationship between the reinforcing value of food and energy intake (Epstein et al, 2004(Epstein et al, , 2007, and A1ϩ individuals show abnormal reward processing and formation of stimulus-cue associations during learning (Cohen et al, 2005;Klein et al, 2007;Jocham et al, 2009;Felsted et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…Additionally, satiety after a meal attenuated the NAc response to high-calorie food images, which also correlated with eating behavior. 20 Thus, change in the activity of these regions is linked to change in behavior, making them a promising target for intervention.…”

Section: Radiological Evidencementioning

confidence: 99%

Deep brain stimulation for obesity: rationale and approach to trial design

Ho¹,

Sussman²,

Pendharkar³

et al. 2015

FOC

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Obesity is one of the most serious public health concerns in the US. While bariatric surgery has been shown to be successful for treatment of morbid obesity for those who have undergone unsuccessful behavioral modification, its associated risks and rates of relapse are not insignificant. There exists a neurological basis for the binge-like feeding behavior observed in morbid obesity that is believed to be due to dysregulation of the reward circuitry. The authors present a review of the evidence of the neuroanatomical basis for obesity, the potential neural targets for deep brain stimulation (DBS), as well as a rationale for DBS and future trial design. Identification of an appropriate patient population that would most likely benefit from this type of therapy is essential. There are also significant cost and ethical considerations for such a neuromodulatory intervention designed to alter maladaptive behavior. Finally, the authors present a consolidated set of inclusion criteria and study end points that should serve as the basis for any trial of DBS for obesity.

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“…This study adds to a growing body of work where fMRI has been used to study the brain response to physiological stimuli such as fasting/refeeding (4); to specific hormones such as leptin (5), ghrelin (6), peptide tyrosine tyrosine (7), and GLP-1 (8); to therapeutic interventions such as caloric restriction (9), weight loss maintenance (10), sibutramine (11), and Roux-en-Y bypass surgery (12,13); and to the effects of common (14) and rare obesityassociated genetic variants (15,16).…”

mentioning

confidence: 99%