Dataset Information

Regulation of Brown Adipose Tissue Activity by Interoceptive CNS Pathways: The interaction between Brain and Periphery.

ABSTRACT: To maintain thermal homeostasis, specific thermogenic tissues are under the control of central thermoregulatory networks that regulate the body's response to thermal challenges. One of these mechanisms involves non-shivering thermogenesis in brown adipose tissue (BAT), which is activated in cold environments in order to defend the body against physical damage as a result of hypothermia. The objective of our study was to assess the interaction between CNS thermoregulatory pathways and sympathetic innervation in BAT during a cold exposure paradigm. Our results show that an innocuous whole-body cooling paradigm induces significant differences in fMRI BOLD signal at the location of the right anterior insula and the red nucleus/substantia nigra region, between lean subjects with high levels of sympathetic innervation in supraclavicular BAT (BAT+ group), and subjects with low levels of sympathetic innervation (BAT- group). Specifically, results indicate significantly larger fMRI BOLD signal changes between periods of cooling and warming of the skin in the BAT+ (as compared to BAT-) group at the location of the right anterior insula. In contrast, the BAT+ group showed significantly smaller fMRI BOLD signal changes in the midbrain between periods of skin cooling and warming. Our findings are consistent with a hierarchical thermoregulatory control system that involves the initiation of inhibitory signals from the right anterior insula toward midbrain areas that normally exert tonic inhibition on the medullary raphe, from where BAT is directly innervated. Our data suggests that exposure to cold elicits differential neuronal activity in interoceptive regulatory centers of subjects with high and low level of sympathetic innervation. As a result, the variability of cold-activated BAT mass observed in humans might be, in part, yoked to different sensitivities of interoceptive cortical brain areas to skin temperature changes.

SUBMITTER: Muzik O

PROVIDER: S-EPMC5696740 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Regulation of Brown Adipose Tissue Activity by Interoceptive CNS Pathways: The interaction between Brain and Periphery.

Muzik Otto O Diwadkar Vaibhav A VA

Frontiers in neuroscience 20171116

To maintain thermal homeostasis, specific thermogenic tissues are under the control of central thermoregulatory networks that regulate the body's response to thermal challenges. One of these mechanisms involves non-shivering thermogenesis in brown adipose tissue (BAT), which is activated in cold environments in order to defend the body against physical damage as a result of hypothermia. The objective of our study was to assess the interaction between CNS thermoregulatory pathways and sympathetic ...[more]

PMID: 29200996

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Project description:BACKGROUND: Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. The mouse Fat-Specific protein 27 (FSP27), a member of the cell death-inducing DFF45-like effector (CIDE) family, is expressed in both BAT and WAT and is associated with lipid droplets. Over-expression of FSP27 promotes lipid storage, whereas FSP27 deficient mice have improved insulin sensitivity and are resistant to diet-induced obesity. In addition, FSP27-deficient white adipocytes have reduced lipid storage, smaller lipid droplets, increased mitochondrial activity and a higher expression of several BAT-selective genes. To elucidate the molecular mechanism by which FSP27 controls lipid storage and gene expression in WAT and BAT, we systematically analyzed the gene expression profile of FSP27-deficient WAT by microarray analysis and compared the expression levels of a specific set of genes in WAT and BAT by semi-quantitative real-time PCR analysis. RESULTS: BAT-selective genes were significantly up-regulated, whereas WAT-selective genes were down-regulated in the WAT of FSP27-deficient mice. The expression of the BAT-selective genes was also dramatically up-regulated in the WAT of leptin/FSP27 double deficient mice. In addition, the expression levels of genes involved in multiple metabolic pathways, including oxidative phosphorylation, the TCA cycle, fatty acid synthesis and fatty acid oxidation, were increased in the FSP27-deficient WAT. In contrast, the expression levels for genes involved in extracellular matrix remodeling, the classic complement pathway and TGF-beta signaling were down-regulated in the FSP27-deficient WAT. Most importantly, the expression levels of regulatory factors that determine BAT identity, such as CEBP alpha/beta, PRDM16 and major components of the cAMP pathway, were markedly up-regulated in the WAT of FSP27-deficient mice. The expression levels of these regulatory factors were also up-regulated in leptin/FSP27 double deficient mice. Interestingly, distinct gene expression profiles were observed in the BAT of FSP27-deficient mice. Taken together, these data suggest that the WAT of FSP27-deficient mice have a gene expression profile similar to that of BAT. CONCLUSIONS: FSP27 acts as a molecular determinant that controls gene expression for a diversity of metabolic and signaling pathways and, in particular, the expression of regulatory factors, including CEBP alpha/beta, PRDM16 and components of the cAMP signaling pathway, that control the identity of WAT and BAT.

Dataset Information

Regulation of Brown Adipose Tissue Activity by Interoceptive CNS Pathways: The interaction between Brain and Periphery.

Publications

Regulation of Brown Adipose Tissue Activity by Interoceptive CNS Pathways: The interaction between Brain and Periphery.

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