Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism

Abstract

Objective: Food intake is regulated by factors that modulate caloric requirements as well as food's reinforcing properties. In this study, we measured brain glucose utilization to an olfactory stimulus (bacon scent), and we examined the role of food restriction and genetic predisposition to obesity on such brain metabolic activity. Methods: Zucker obese (Ob) and lean (Le) rats were divided into four groups: (1) Ob ad-libitum fed, (2) Ob food restricted (70% of ad libitum), (3) Le ad-libitum fed and (4) Le food restricted. Rats were scanned using m-positron emission tomography and 2-[ 18 F]-fluoro-2-deoxy-D-glucose under two conditions: (1) baseline scan (no stimulation) and (2) challenge scan (food stimulation, FS). Results: FS resulted in deactivation of the right and left hippocampus. Ob rats showed greater changes with FS than Le rats (deactivation of hippocampus and activation of the medial thalamus) and Ob but not Le animals deactivated the frontal cortex and activated the superior colliculus. Access to food resulted in an opposite pattern of metabolic changes to the food stimuli in olfactory nucleus (deactivated in unrestricted and activated in restricted) and in right insular/parietal cortex (activated in unrestricted and deactivated in restricted). In addition, restricted but not unrestricted animals activated the medial thalamus. Conclusions: The greater changes in the Ob rats suggest that leptin modulates the regional brain responses to a familiar food stimulus. Similarly, the differences in the pattern of responses with food restriction suggest that FS is influenced by access to food conditions. The main changes with FS occurred in the hippocampus, a region involved in memory, the insular cortex, a region involved with interoception (perception of internal sensations), the medial thalamus (region involved in alertness) and in regions involved with sensory perception (olfactory bulb, olfactory nucleus, occipital cortex, superior colliculus and parietal cortex), which corroborates their relevance in the perception of food.

Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

“…Afterwards, mice were anesthetized with isoflurane (1.5%) and scanned for 20 minutes as above. All images were reconstructed using the maximum a posteriori (MAP) algorithm, as previously described (8). After reconstruction, images were spatially processed and normalized using the Pixel-Wise Modeling Software Suite (PMOD; PMOD Inc.) to a rat brain MRI template set to Paxinos and Watson stereotaxic coordinates (12).…”

“…Only clusters comprising with a P value of less than 0.05 were reported. Additionally, in an effort to limit false positives, we only reported significant clusters comprising of greater than 100 contiguous voxels as previously described (7,8). The maps surviving the P = 0.05 threshold were then analyzed using paired t tests (vehicle > CNO and vehicle < CNO for the groups: Pdyn-hM4Di, Penk-hM4Di, C57BL/6 mice) and (left hemisphere vs. right hemisphere for the rats used in the vibrissae stimulation experiment).…”

“…Importantly, a recent study showed that light delivery in the absence of optogenetic stimulation induced strong local fMRI responses in the stimulated site (3). To overcome these limitations, we combined designer receptor exclusively activated by designer drug (DREADD) technology (4), which allows remote in vivo control of cell-specific firing (5), together with behavioral imaging using μPET and [ 18 F]fluorodeoxyglucose (FDG) to measure regional brain glucose metabolism, which is a direct marker of brain function (6)(7)(8)(9). This approach, termed DREADD-assisted metabolic mapping (DREAMM), was used to map functional brain anatomy associated with inhibiting the activity of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) in the medial nucleus accumbens shell (NAcSh), highly implicated in neuropsychiatric disorders.…”

Dopamine-related frontostriatal abnormalities in obesity and binge-eating disorder: Emerging evidence for developmental psychopathology

“…Conversely, PET imaging in rodents has recapitulated some of the clinical observations made in obese and BED populations, and for certain radiotracers such as [ 18 F]FDG (used to measure brain glucose metabolism) and [ 11 C]raclopride (used to measure D2R binding potential) the measurements can be made in awake animals. One PET study done in genetically obese rats (leptin-receptor deficient) examined the brain metabolic responses to food stimuli in awake rats comparing metabolism in the absence and in the presence of a bacon scent (Thanos et al, 2008a). This study found that while bacon scent decreased glucose metabolism (marker of activity) in frontal cortex in both obese and lean rats, the decreases were significantly greater in the obese group.…”

“…Obesity-related deficits in striatal dopamine D2 receptors (D2R) are conserved across species: (A) representative positron emission tomography brain scans and (B) Bmax/Kd values of D2R binding in lean and obese humans (Wang et al, 2001) and rats (Thanos et al, 2008). …”