Neuropeptide Y Plays an Important Role in the Relationship Between Brain Glucose Metabolism and Brown Adipose Tissue Activity in Healthy Adults: A PET/CT Study

Abstract

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.

Mechanism of action of the bile acid receptor TGR5 in obesity

“…Notably, studies have shown that as the centre of food intake, thermoregulation and metabolism, there is a negative correlation in the hypothalamus between NPY and BAT activity. Knockout of NPY effectively promoted the expression of BAT in inguinal and interscapular fat, increased energy consumption, improved glucose homeostasis and enhanced insulin sensitivity 195 , 196 . By linking these data, we speculate that an as-yet undefined gut-brain-fat axis may be involved in the anti-obesity mechanism.…”

Effects of multi-organ crosstalk on the physiology and pathology of adipose tissue

“…And glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but significantly decreased isoprenaline-stimulated respiration and UCP-1 in murine primary brown and beige adipocytes ( 95 ). A study using positron emission tomography/computed tomography (PET/CT) to noninvasively study BAT activity and brain glucose metabolism in vivo found that neuropeptide Y (NPY) secreted by the hypothalamus mediates brain glucose metabolism consistent with BAT activity in healthy adults ( 96 ) ( Figure 2 ).…”