The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight1, 2. However, in the current ‘obesogenic’ human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions3. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans1, 4, 5. Here we show, using functional magnetic resonance imaging, that peptide YY3–36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.
"europeptide Y ( NPY ) neurons in the arcuate nucleus of the hypothalamus inhibiting food intake ( Batterham et al . , 2002 ) . In humans , functional magnetic resonance imaging could demonstrate activation of specific brain areas after exogenous administration of PYY 3 - 36 and GLP - 1 7 - 36 , similar to those observed after regular food intake ( Batterham et al . , 2007 ; De Silva et al . , 2011 ) . Recent research in mice suggested that PPY acts also on GLP - 1 secretion through activation of peripheral Y2R ( Chandarana et al . , 2013 ) ."
"Another important piece of evidence supporting a physiological role of PYY 3–36 in the control of food intake stems from recent functional neuroimaging studies demonstrating that physiological levels of PYY 3–36, besides activating homeostatic brain areas such as the hypothalamus, also activate numerous other cortical and subcortical brain areas, some of which play crucial roles in central reward processing (Batterham et al., 2007; De Silva et al., 2011; Weise et al., 2012). For example, Batterham et al. (2007) observed that exogenous PYY 3–36 infusion in humans, which resulted in circulating PYY 3–36 concentrations that were similar to those observed post-prandially, modulated neuronal activity within corticolimbic and higher cortical brain areas, including hypothalamus, striatum and orbitofrontal cortex. While highlighting extrahypothalamic effects of PYY 3–36 at physiologically relevant concentrations , the data also highlight the possibility that physiological concentrations of PYY 3–36 modulate behavioral functions beyond food intake. "
"The effects of two different insulin regimens on fMRI-measured BOLD signal have not been investigated before. Other fMRI studies using a parallel group or paired designs to compare two groups or post-pre intervention, respectively, required 6-26 individuals to show meaningful results , , . Based on these studies and our premise that the difference on brain activation between the two insulin regimens would be modest (15%, standard deviation 20%), and assuming a power of .8 and a two-sided .05 "
[Show abstract][Hide abstract] ABSTRACT: Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli.
PLoS ONE 04/2014; 9(4):e94483. DOI:10.1371/journal.pone.0094483 · 3.23 Impact Factor
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