Dataset Information

Stability in brain glucose metabolism following brown adipose tissue inactivation in chinese adults.

ABSTRACT:

Background and purpose

The thermogenesis of BAT is believed to be controlled through some pathways initiated in the brain, though the changes in brain activity among different states of BAT-positive subjects are still unclear. We hypothesized that some significant differences of regional cerebral metabolism between various groups were related to the BAT activities regardless of temperature changes.

Materials and methods

Relative regional cerebral glucose metabolism was compared between 15 healthy subjects with activated BAT and 30 healthy controls without activated BAT by using a brain FDG-PET scan. A follow-up PET scan was performed to assess metabolic changes of the brain when BAT activity was eliminated by heat exposure.

Results

Compared with controls, BAT-positive subjects exhibited lower activity in the inferior parietal lobule, limbic system, and frontal lobe and higher activity in the precuneus before heat exposure. Compared with the BAT elimination status, subjects with activated BAT showed a decreased metabolism in the parietal lobe, frontal lobe, culmen, cingulate gyrus, and sublobar region. Compared with controls, BAT-positive subjects after BAT inactivation had significant hypometabolic areas in the temporal lobe and limbic lobe and hypermetabolic areas in the parietal lobe.

Conclusions

Our findings illustrate that changes of regional cerebral metabolism are related to BAT activities regardless of temperature changes. This before-after controlled study supports the finding that the brain responses appear to be active in modulating the metabolic function of BAT activity.

SUBMITTER: Miao Q

PROVIDER: S-EPMC7966559 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionBrown adipose tissue (BAT) becomes the favorite target for preventing and treating metabolic diseases because the activated BAT can produce heat and consume energy. The brain, especially the hypothalamus, which secretes Neuropeptide Y (NPY), is speculated to regulate BAT activity. However, whether NPY is involved in BAT activity's central regulation in humans remains unclear. Thus, it's essential to explore the relationship between brain glucose metabolism and human BAT activity.MethodsA controlled study with a large sample of healthy adults used Positron emission tomography/computed tomography (PET/CT) to noninvasively investigate BAT's activity and brain glucose metabolism in vivo. Eighty healthy adults with activated BAT according to the PET/CT scan volunteered to be the BAT positive group, while 80 healthy adults without activated BAT but with the same gender, similar age, and BMI, scanning on the same day, were recruited as the control (BAT negative). We use Statistical parametric mapping (SPM) to analyze the brain image data, Picture Archiving & Communication System (PACS), and PET/CT Viewer software to calculate the semi-quantitative values of brain glucose metabolism and BAT activity. ELISA tested the levels of fasting plasma NPY. The multiple linear regression models were used to analyze the correlation between brain glucose metabolism, the level of NPY, and the BAT activity in the BAT positive group.Results(1) Compared with controls, BAT positive group showed significant metabolic decreases mainly in the right Insula (BA13a, BA13b) and the right claustrum (uncorrected P <0.01, adjusted BMI). (2) The three brain regions' semi-quantitative values in the BAT positive group were significantly lower than the negative group (all P values < 0.05). (3) After adjusting for age, gender, BMI, and outside temperature, there was a negative correlation between brain metabolic values and BAT activity (all P values < 0.05). However, after further adjusting for NPY level, there were no significant differences between the BA13b metabolic values and BAT activity (P>0.05), while the correlation between the BA13a metabolic values and BAT activity still was significant (P< 0.05).ConclusionsRegional brain glucose metabolism is closely related to healthy adults' BAT activity, which may be mediated by NPY.

Project description:ObjectiveBrown adipose tissue (BAT) thermogenesis is critical in maintaining body temperature. The dorsomedial hypothalamus (DMH) integrates cutaneous thermosensory signals and regulates adaptive thermogenesis. Here, we study the function and synaptic connectivity of input from DMH cholinergic neurons to sympathetic premotor neurons in the raphe pallidus (Rpa).MethodsIn order to selectively manipulate DMH cholinergic neuron activity, we generated transgenic mice expressing channelrhodopsin fused to yellow fluorescent protein (YFP) in cholinergic neurons (choline acetyltransferase (ChAT)-Cre::ChR2-YFP) with the Cre-LoxP technique. In addition, we used an adeno-associated virus carrying the Cre recombinase gene to delete the floxed Chat gene in the DMH. Physiological studies in response to optogenetic stimulation of DMH cholinergic neurons were combined with gene expression and immunocytochemical analyses.ResultsA subset of DMH neurons are ChAT-immunopositive neurons. The activity of these neurons is elevated by warm ambient temperature. A phenotype-specific neuronal tracing shows that DMH cholinergic neurons directly project to serotonergic neurons in the Rpa. Optical stimulation of DMH cholinergic neurons decreases BAT activity, which is associated with reduced body core temperature. Furthermore, elevated DMH cholinergic neuron activity decreases the expression of BAT uncoupling protein 1 (Ucp1) and peroxisome proliferator-activated receptor γ coactivator 1 α (Pgc1α) mRNAs, markers of BAT activity. Injection of M2-selective muscarinic receptor antagonists into the 4th ventricle abolishes the effect of optical stimulation. Single cell qRT-PCR analysis of retrogradely identified BAT-projecting neurons in the Rpa shows that all M2 receptor-expressing neurons contain tryptophan hydroxylase 2. In animals lacking the Chat gene in the DMH, exposure to warm temperature reduces neither BAT Ucp1 nor Pgc1α mRNA expression.ConclusionDMH cholinergic neurons directly send efferent signals to sympathetic premotor neurons in the Rpa. Elevated cholinergic input to this area reduces BAT activity through activation of M2 mAChRs on serotonergic neurons. Therefore, the direct DMH(ACh)-Rpa(5-HT) pathway may mediate physiological heat-defense responses to elevated environmental temperature.