Dataset Information

Circulating glucose levels modulate neural control of desire for high-calorie foods in humans.

ABSTRACT: Obesity is a worldwide epidemic resulting in part from the ubiquity of high-calorie foods and food images. Whether obese and nonobese individuals regulate their desire to consume high-calorie foods differently is not clear. We set out to investigate the hypothesis that circulating levels of glucose, the primary fuel source for the brain, influence brain regions that regulate the motivation to consume high-calorie foods. Using functional MRI (fMRI) combined with a stepped hyperinsulinemic euglycemic-hypoglycemic clamp and behavioral measures of interest in food, we have shown here that mild hypoglycemia preferentially activates limbic-striatal brain regions in response to food cues to produce a greater desire for high-calorie foods. In contrast, euglycemia preferentially activated the medial prefrontal cortex and resulted in less interest in food stimuli. Indeed, higher circulating glucose levels predicted greater medial prefrontal cortex activation, and this response was absent in obese subjects. These findings demonstrate that circulating glucose modulates neural stimulatory and inhibitory control over food motivation and suggest that this glucose-linked restraining influence is lost in obesity. Strategies that temper postprandial reductions in glucose levels might reduce the risk of overeating, particularly in environments inundated with visual cues of high-calorie foods.

SUBMITTER: Page KA

PROVIDER: S-EPMC3195474 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Circulating glucose levels modulate neural control of desire for high-calorie foods in humans.

Page Kathleen A KA Seo Dongju D Belfort-DeAguiar Renata R Lacadie Cheryl C Dzuira James J Naik Sarita S Amarnath Suma S Constable R Todd RT Sherwin Robert S RS Sinha Rajita R

The Journal of clinical investigation 20110919 10

Obesity is a worldwide epidemic resulting in part from the ubiquity of high-calorie foods and food images. Whether obese and nonobese individuals regulate their desire to consume high-calorie foods differently is not clear. We set out to investigate the hypothesis that circulating levels of glucose, the primary fuel source for the brain, influence brain regions that regulate the motivation to consume high-calorie foods. Using functional MRI (fMRI) combined with a stepped hyperinsulinemic euglyce ...[more]

PMID: 21926468

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Project description:Several public health departments throughout North America have responded to the obesity epidemic by mandating that restaurants publish calories at the point of purchase-with the intention of encouraging healthier food decisions. To help determine whether accompanying calorie information successfully changes a food's appetitive value, this study investigated the influence of calorie information on brain responses to food images. During functional magnetic resonance imaging (fMRI) scanning, dieting (N = 22) and non-dieting (N = 20) participants viewed pictures of food with and without calorie information and rated their desire to eat the food. When food images were paired with calorie information, not only did self-reported desire to eat the food decrease, but reward system activation (Neurosynth-defined from the term "food") decreased and control system activation (the fronto-parietal [FP] control system) increased. Additionally, a parametric modulation of reward activation by food preferences was attenuated in the context of calorie information. Finally, whole brain multivariate pattern analysis (MVPA) revealed patterns of activation in a region of the reward system-the orbitofrontal cortex (OFC)-that were more similar for food images presented with and without calorie information in dieting than non-dieting participants, suggesting that dieters may spontaneously consider calorie information when viewing food. Taken together, these results suggest that calorie information may alter brain responses to food cues by simultaneously reducing reward system activation and increasing control system activation. Moreover, individuals with greater experience or stronger motivations to consider calorie information (i.e., dieters) may more naturally do so, as evidenced by a greater degree of representational similarity between food images with and without calorie information. Combining an awareness of calories with the motivation to control them may more effectively elicit diet-related behavior change.

Project description:Skeletal metastases of breast cancer and subsequent osteolysis connote a dramatic change in the prognosis for the patient and significantly increase the morbidity associated with disease. The cytokine interleukin 8 (IL-8/CXCL8) is able to directly stimulate osteoclastogenesis and bone resorption in mouse models of breast cancer bone metastasis. In this study, we determined whether circulating levels of IL-8 were associated with increased bone resorption and breast cancer bone metastasis in patients and investigated IL-8 action in vitro and in vivo in mice. Using breast cancer patient plasma (36 patients), we identified significantly elevated IL-8 levels in bone metastasis patients compared with patients lacking bone metastasis (p<0.05), as well as a correlation between plasma IL-8 and increased bone resorption (p<0.05), as measured by NTx levels. In a total of 22 ER+ and 15 ER- primary invasive ductal carcinomas, all cases examined stained positive for IL-8 expression. In vitro, human MDA-MB-231 and MDA-MET breast cancer cell lines secrete two distinct IL-8 isoforms, both of which were found to stimulate osteoclastogenesis. However, the more osteolytic MDA-MET-derived full length IL-8(1-77) had significantly higher potency than the non-osteolytic MDA-MB-231-derived IL-8(6-77), via the CXCR1 receptor. MDA-MET breast cancer cells were injected into the tibia of nude mice and 7days later treated daily with a neutralizing IL-8 monoclonal antibody. All tumor-injected mice receiving no antibody developed large osteolytic bone tumors, whereas 83% of the IL-8 antibody-treated mice had no evidence of tumor at the end of 28days and had significantly increased survival. The pro-osteoclastogenic activity of IL-8 in vivo was confirmed when transgenic mice expressing human IL-8 were examined and found to have a profound osteopenic phenotype, with elevated bone resorption and inherently low bone mass. Collectively, these data suggest that IL-8 plays an important role in breast cancer osteolysis and that anti-IL-8 therapy may be useful in the treatment of the skeletal related events associated with breast cancer.

Dataset Information

Circulating glucose levels modulate neural control of desire for high-calorie foods in humans.

Publications

Circulating glucose levels modulate neural control of desire for high-calorie foods in humans.

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