Control of Energy Expenditure by AgRP Neurons of the Arcuate Nucleus: Neurocircuitry, Signaling Pathways, and Angiotensin

Morselli, Lisa L.; Claflin, Kristin E.; Cui, Huxing; Grobe, Justin L

doi:10.1007/s11906-018-0824-8

Cited by 26 publications

(23 citation statements)

References 74 publications

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“…Among them, hypothalamic ARC, attached to the bottom of the third ventricle, is of crucial importance to integration of peripheral metabolic signals on energy status [ 10 ]. Recent research shows that distinct neuronal populations in hypothalamic ARC, such as proopiomelanocortin (POMC) neurons and agouti-related protein (AgRP) neurons, regulate BAT thermogenesis via activation of sympathetic nervous system [ 11 ]. These neurons project mainly to second-order neurons in the hypothalamic DMN and PVN, leading to an integrated response on BAT thermogenesis and energy expenditure [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of (−)-Epigallocatechin Gallate (EGCG) on Energy Expenditure and Microglia-Mediated Hypothalamic Inflammation in Mice Fed a High-Fat Diet

Zhou

Mao

et al. 2018

Nutrients

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Obesity is an escalating global epidemic caused by an imbalance between energy intake and expenditure. (−)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been reported to be conducive to preventing obesity and alleviating obesity-related chronic diseases. However, the role of EGCG in energy metabolism disorders and central nervous system dysfunction induced by a high-fat diet (HFD) remains to be elucidated. The aim of this study was to evaluate the effects of EGCG on brown adipose tissue (BAT) thermogenesis and neuroinflammation in HFD-induced obese C57BL/6J mice. Mice were randomly divided into four groups with different diets: normal chow diet (NCD), normal chow diet supplemented with 1% EGCG (NCD + EGCG), high-fat diet (HFD), and high-fat diet supplemented with 1% EGCG (HFD + EGCG). Investigations based on a four-week experiment were carried out including the BAT activity, energy consumption, mRNA expression of major inflammatory cytokines in the hypothalamus, nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and immunofluorescence staining of microglial marker Iba1 in hypothalamic arcuate nucleus (ARC). Experimental results demonstrated that dietary supplementation of EGCG significantly inhibited HFD-induced obesity by enhancing BAT thermogenesis, and attenuated the hypothalamic inflammation and microglia overactivation by regulating the NF-κB and STAT3 signaling pathways.

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Section: Introductionmentioning

confidence: 99%

Effects of (−)-Epigallocatechin Gallate (EGCG) on Energy Expenditure and Microglia-Mediated Hypothalamic Inflammation in Mice Fed a High-Fat Diet

Zhou

Mao

et al. 2018

Nutrients

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show abstract

“…It has also been reported that asip can affect melanocyte differentiation and maturation in mice [ 49 ]. Meanwhile, mammalian agrp is mainly expressed in the hypothalamus where it has predominantly been explored in the context of regulating energy balance [ 50 , 51 ]. In contrast to tetrapods, teleosts have four endogenous antagonists: asip1, asip2, agrp1 and agrp2 due to genome duplication [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic deciphering of the antagonistic activities of the melanin-concentrating hormone and melanocortin pathways in skin pigmentation

et al. 2020

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The genetic origin of human skin pigmentation remains an open question in biology. Several skin disorders and diseases originate from mutations in conserved pigmentation genes, including albinism, vitiligo, and melanoma. Teleosts possess the capacity to modify their pigmentation to adapt to their environmental background to avoid predators. This background adaptation occurs through melanosome aggregation (white background) or dispersion (black background) in melanocytes. These mechanisms are largely regulated by melanin-concentrating hormone (MCH) and α-melanocyte–stimulating hormone (α-MSH), two hypothalamic neuropeptides also involved in mammalian skin pigmentation. Despite evidence that the exogenous application of MCH peptides induces melanosome aggregation, it is not known if the MCH system is physiologically responsible for background adaptation. In zebrafish, we identify that MCH neurons target the pituitary gland-blood vessel portal and that endogenous MCH peptide expression regulates melanin concentration for background adaptation. We demonstrate that this effect is mediated by MCH receptor 2 (Mchr2) but not Mchr1a/b. mchr2 knock-out fish cannot adapt to a white background, providing the first genetic demonstration that MCH signaling is physiologically required to control skin pigmentation. mchr2 phenotype can be rescued in adult fish by knocking-out pomc, the gene coding for the precursor of α-MSH, demonstrating the relevance of the antagonistic activity between MCH and α-MSH in the control of melanosome organization. Interestingly, MCH receptor is also expressed in human melanocytes, thus a similar antagonistic activity regulating skin pigmentation may be conserved during evolution, and the dysregulation of these pathways is significant to our understanding of human skin disorders and cancers.

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“…Previous studies provided evidence that AgRP was only synthesized in NPYcontaining cell bodies that were located in the ventromedial part of the arcuate nucleus in the hypothalamus. 25 The AgRP is an effective peptide that promotes appetite, and the appetite-stimulating effect of AgRP was activated by the hormone ghrelin, which further increased food intake when AgRP was overexpressed. 26 Similarly, Zhang et al 27 also showed that AgRP was closely associated with glucose homeostasis and insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Altered features of neurotransmitters: NPY, α-MSH, and AgRP in type 2 diabetic patients with hypertension

Guo

et al. 2020

J Int Med Res

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Objective To investigate the features of neuropeptide Y (NPY), α-melanocyte stimulating hormone (α-MSH), and agouti-related protein (AgRP) in type 2 diabetes mellitus (T2DM) patients with hypertension. Methods Patients with T2DM (n = 384) and healthy volunteers (n = 80) were enrolled into this study. Serum NPY, α-MSH, and AgRP levels were detected using ELISA. Results Significantly higher NPY and lower α-MSH and AgRP levels were observed in patients with diabetes compared with those without diabetes, and the mean NPY levels increased, while α-MSH and AgRP levels decreased, with the development of hypertension compared with diabetic patients without hypertension. α-MSH and AgRP levels decreased with an increase in blood pressure in hypertension compared with the non-hypertension patients. Multiple stepwise linear regression analysis showed that NPY, α-MSH, and AgRP levels were closely associated with blood pressure and glucose control. Receiver operating characteristic (ROC) curve analyses indicated that α-MSH may be a better marker compared with NPY and AgRP for regulating glucose and blood pressure and to distinguish between T2DM patients with and without hypertension. Conclusion NPY, α-MSH, and AgRP might play different roles and be closely related to the occurrence and development of diabetes and hypertension.

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Control of Energy Expenditure by AgRP Neurons of the Arcuate Nucleus: Neurocircuitry, Signaling Pathways, and Angiotensin

Cited by 26 publications

References 74 publications

Effects of (−)-Epigallocatechin Gallate (EGCG) on Energy Expenditure and Microglia-Mediated Hypothalamic Inflammation in Mice Fed a High-Fat Diet

Effects of (−)-Epigallocatechin Gallate (EGCG) on Energy Expenditure and Microglia-Mediated Hypothalamic Inflammation in Mice Fed a High-Fat Diet

Genetic deciphering of the antagonistic activities of the melanin-concentrating hormone and melanocortin pathways in skin pigmentation

Altered features of neurotransmitters: NPY, α-MSH, and AgRP in type 2 diabetic patients with hypertension

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