Traveling from the hypothalamus to the adipose tissue: The thermogenic pathway

Contreras, Cristina; Nogueiras, Rubén; Diéguez, Carlos; Rahmouni, Kamal; López, Miguel

doi:10.1016/j.redox.2017.04.019

Cited by 81 publications

(80 citation statements)

References 190 publications

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“…First, RIP‐Cre neurons in ARC are heterogeneous and GABAergic (i.e., release the inhibitory neurotransmitter GABA) in nature , whereas the majority of VMH neurons are glutamatergic (i.e., release the excitatory neurotransmitter glutamine) . Second, RIP‐Cre neurons in ARC project to the PVH, while VMH is anatomically connected to different areas of brain stem such as RPa and inferior olive . Third, ARC contains heterogeneous neuronal population including POMC‐, NPY‐, AgRP‐expressing neurons , whereas VMH mainly contains SF1‐ and Nkx2.1‐expressing neurons .…”

Section: Discussionmentioning

confidence: 99%

Activation of hypothalamic RIP ‐Cre neurons promotes beiging of WAT via sympathetic nervous system

Wang

et al. 2018

EMBO Reports

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Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2-AMPK signaling axis is crucial for this defending mechanism to cold and obesity.

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Section: Discussionmentioning

confidence: 99%

Activation of hypothalamic RIP ‐Cre neurons promotes beiging of WAT via sympathetic nervous system

Wang

et al. 2018

EMBO Reports

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“…Researchers using PRV injected into WAT have described the origins of the central circuits in the hypothalamic paraventricular, suprachiasmatic, arcuate and dorsomedial nuclei, lateral hypothalamic areas, which ultimately terminate in WAT and are implicated in lipid mobilization (Adler, Hollis, Clarke, Grattan, & Oldfield, ; Bamshad, Aoki, Adkison, Warren, & Bartness, ; Nguyen et al, ). BAT is a thermogenic tissue involved in rewarming, nonshivering thermogenesis, diet‐induced thermogenesis, and febrile responses (Contreras, Nogueiras, Diéguez, Rahmouni, & López, ). SNS innervation provides the principal stimulus of BAT thermogenesis.…”

Section: Introductionmentioning

confidence: 99%

Convergent neuronal projections from paraventricular nucleus, parabrachial nucleus, and brainstem onto gastrocnemius muscle, white and brown adipose tissue in male rats

Doslikova

Tchir

McKinty

et al. 2019

J of Comparative Neurology

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When energy balance is altered by aerobic exercise, starvation, and cold exposure, for example, there appears to be coordination of the responses of skeletal muscle, white adipose (WAT), and brown adipose (BAT) tissues. We hypothesized that WAT, BAT, and skeletal muscle may share an integrated regulation by the central nervous system (CNS); specifically, that neurons in brain regions associated with energy balance would possess neuroanatomical connections to permit coordination of multiple, complementary responses in these downstream tissues. To study this, we used trans‐neuronal viral retrograde tract tracing, using isogenic strains of pseudorabies virus (PRV) with distinct fluorescent reporters (either eGFP or mRFP), injected pairwise into male rat gastrocnemius, subcutaneous WAT and interscapular BAT, coupled with neurochemical characterization of specific cell populations for cocaine‐ and amphetamine‐related transcript (CART), oxytocin (OX), corticotrophin releasing hormone (CRH) and calcitonin gene‐related peptide (CGRP). Cells in the paraventricular (PVN) and parabrachial (PBN) nuclei and brainstem showed dual projections to muscle + WAT, muscle + BAT, and WAT + BAT. Dual PRV‐labeled cells were found in parvocellular, magnocellular and descending/pre‐autonomic regions of the PVN, and multiple structural divisions of the PBN and brainstem. In most PBN subdivisions, more than 50% of CGRP cells dually projected to muscle + WAT and muscle + BAT. Similarly, 31–68% of CGRP cells projected both to WAT + BAT. However, dual PRV‐labeled cells in PVN only occasionally expressed OX or CRH but not CART. These studies reveal for the first time both separate and shared outflow circuitries among skeletal muscle and subcutaneous WAT and BAT.

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“…The PVN is a major integrating center for both cardiovascular and metabolic responses and AT1 receptors have been localized in the PVN. 30,31 As above, there was no increase in total renin mRNA in the arcuate nucleus, but again, the redistribution of Ren-a/Ren-b may provide a source of extracellular prorenin/renin needed for local Ang-II synthesis in this nucleus. This may be significant as AT1 receptor mRNA are localized on some leptin receptor-containing neurons in the arcuate nucleus which regulate RMR.…”

Section: Discussionmentioning

confidence: 63%

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism

et al. 2017

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The brain specific isoform of renin (Ren-b), has been proposed as a negative regulator of the brain renin-angiotensin system (RAS). We analyzed mice with a selective deletion of Ren-b which preserved expression of the classical renin (Ren-a) isoform. We reported that Ren-bNull mice exhibited central RAS activation and hypertension through increased expression of Ren-a, but the dipsogenic and metabolic effects in Ren-bNull mice are unknown. Fluid intake was similar in control and Ren-bNull mice at baseline and both exhibited an equivalent dipsogenic response to DOCA-salt. Dehydration promoted increased water intake in Ren-bNull mice, particularly after DOCA-salt. Ren-bNull and control mice exhibited similar body weight when fed a chow diet. However, when fed a high fat diet, male Ren-bNull mice gained significantly less weight than control mice, an effect blunted in females. This difference was not due to changes in food intake, energy absorption or physical activity. Ren-bNull mice exhibited increased resting metabolic rate concomitant with increased uncoupled protein 1 expression and sympathetic nerve activity to the interscapular brown adipose tissue (BAT), suggesting increased thermogenesis. Ren-bNull mice were modestly intolerant to glucose and had normal insulin sensitivity. Another mouse model with markedly enhanced brain RAS activity (sRA mice) exhibited pronounced insulin sensitivity concomitant with increased BAT glucose uptake. Altogether, these data support the hypothesis that the brain RAS regulates energy homeostasis by controlling resting metabolic rate, and that Ren-b deficiency increases brain RAS activity. Thus, the relative level of expression of Ren-b and Ren-a may control activity of the brain RAS.

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Traveling from the hypothalamus to the adipose tissue: The thermogenic pathway

Cited by 81 publications

References 190 publications

Activation of hypothalamic RIP ‐Cre neurons promotes beiging of WAT via sympathetic nervous system

Activation of hypothalamic RIP ‐Cre neurons promotes beiging of WAT via sympathetic nervous system

Convergent neuronal projections from paraventricular nucleus, parabrachial nucleus, and brainstem onto gastrocnemius muscle, white and brown adipose tissue in male rats

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism

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