Knockdown of NPY Expression in the Dorsomedial Hypothalamus Promotes Development of Brown Adipocytes and Prevents Diet-Induced Obesity

Chao, Pei Ting; Yang, Liang; Aja, Susan; Moran, Timothy H.; Bi, Sheng

doi:10.1016/j.cmet.2011.02.019

Cited by 186 publications

(227 citation statements)

References 51 publications

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“…These phenomena are inconsistent with the previous findings that NPY has a suppressive role in the BAT thermogenesis when given intraperitoneally [30]. As central activation and suppression of NPY neuron decrease and promote BAT function, respectively [6,8,21], this inconsistency may be explained by the assumption that intraperitoneally administered NPY leads to activation of central NPY neurons. However, central action induced by peripheral NPY remains to be elucidated.…”

Section: Discussioncontrasting

confidence: 81%

Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

et al. 2012

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Section: Discussioncontrasting

confidence: 81%

Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

et al. 2012

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“…Its overexpression causes aggregation of lipid droplets, and decreased expression decreases lipid droplet size while increasing mitochondria quantity [37]. RIP140 and Cidec are almost undetectable in BAT [38,39]. Our results suggest that NPY induces hADSC differentiation into white adipocytes because it increases RIP140 and Cidec expression in a dosedependent manner.…”

Section: Discussionsupporting

confidence: 54%

Neuropeptide Y promotes adipogenic differentiation in primary cultured human adipose-derived stem cells

Liu

Fang

et al. 2018

Endocr J

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Abstract. Neuropeptide Y (NPY) is an important neurotransmitter in the control of energy metabolism. Several studies have shown that obesity is associated with increased levels of NPY in the hypothalamus. We hypothesized that the release of NPY has coordinated and integrated effects on energy metabolism in different tissues, such as adipocyte tissue, resulting in increased energy storage and decreased energy expenditure. Whether NPY has role in the molecular mechanism of human adipocyte tissue remains unclear. We established the model of human adipose derived stem cells (hADSCs) from human adipose tissue and differentiated it into adipocytes in the presence of NPY at different concentrations (10 -15 -10 -6 mmol/L). We then assessed hADSCs proliferation and differentiation by quantifying lipid accumulation and examining the expression levels of related adipocyte markers after differentiation. Furthermore, the specific markers of white adipocyte tissue (WAT) in hADSCs were also analyzed. The results showed that low doses of NPY stimulated hADSCs proliferation (p < 0.05), while high doses of NPY inhibited hADSCs proliferation (p < 0.05). NPY significantly promoted lipid accumulation and increased the size of lipid droplets during human adipogenic differentiation; the levels of adipocyte markers PPAR-γ and C/EBPα were also increased. At the same time, NPY also increased the levels of WAT markers Cidec and RIP140 after adipocyte differentiation. The results suggested high dose NPY inhibits the proliferation of hADSCs while promotes adipocyte differentiation and increases the expression of WAT markers. This may be the reason why increased levels of NPY can lead to a rise in body weight.Key words: Neuropeptide Y, Human adipose-derived stem cells, Adipocyte differentiation, White adipose tissue NEUROPEPTIDE Y (NPY) is a 36-amino acid neuropeptide, which is widely expressed in the central and peripheral nervous system. In the brain, NPY is found in many brain areas [1], including the hypothalamus, dentate gyrus, lateral thalamus and striatum, with the highest concentrations in the arcuate nucleus of the hypothalamus (Arc). NPY is implicated in the regulation of many physiological processes, including food intake and body energy balance. NPY also regulates cardiovascular, gastrointestinal, reproductive, endocrine and behavioural function [2][3][4]. Recently, studies have revealed that administration of NPY has profound metabolic effects throughout the body. One characteristic of obesity is the This overproduction of fat is associated with increased lipogenesis in different organs, such as liver and white adipose tissue (WAT). Several studies found that obesity is associated with elevated levels of NPY in the hypothalamus [5][6][7][8][9]. Adipose tissue is important for regulation of energy metabolism. A disturbance of metabolic processes, such as thermogenesis, lipogenesis and fatty acid oxidation, may contribute to the pathology of obesity. In order to increase our understanding of how NPY could be involved in the adipoc...

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“…44 Importantly, DMH NPY knockdown decreased subcutaneous (IWAT and DWAT) fat mass and increased browning only in these fat pads, but not in EWAT, mesenteric WAT, retroperitoneal WAT or perirenal WAT. 44 The browning was strikingly apparent to the unaided eye and verified by UCP-1-ir, presence of brown adipocyte-like multilocular lipid droplets within these adipocytes, as well as reverse transcription-PCR and the western blot assay for UCP-1 gene expression and protein, respectively. 44 In addition, DMH NPY knockdown increased the gene expression of the 'thermogenic program' (that is, PPARγ and Pgc-1α mRNA) in IWAT 44 ; DWAT was not assayed.…”

Section: Methodsmentioning

confidence: 99%

“…More specifically, when neuropeptide Y (NPY) gene expression (and presumably translation into the NPY protein) within the DMH decreases (with assumed decreases in NPY release at its CNS targets), subcutaneous WAT depots brown. 44 This was demonstrated by injection of adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) into the DMH of laboratory rats and resulted in a specific and marked knockdown of DMH NPY, but not arcuate NPY, compared with DMH injection of the scrambled short hairpin RNA (shRNA) control. 44 Importantly, DMH NPY knockdown decreased subcutaneous (IWAT and DWAT) fat mass and increased browning only in these fat pads, but not in EWAT, mesenteric WAT, retroperitoneal WAT or perirenal WAT.…”

Section: Methodsmentioning

confidence: 99%

“…44 This was demonstrated by injection of adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) into the DMH of laboratory rats and resulted in a specific and marked knockdown of DMH NPY, but not arcuate NPY, compared with DMH injection of the scrambled short hairpin RNA (shRNA) control. 44 Importantly, DMH NPY knockdown decreased subcutaneous (IWAT and DWAT) fat mass and increased browning only in these fat pads, but not in EWAT, mesenteric WAT, retroperitoneal WAT or perirenal WAT. 44 The browning was strikingly apparent to the unaided eye and verified by UCP-1-ir, presence of brown adipocyte-like multilocular lipid droplets within these adipocytes, as well as reverse transcription-PCR and the western blot assay for UCP-1 gene expression and protein, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Neural control of white, beige and brown adipocytes

Bartness

Ryu

2015

Int J Obes Supp

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Reports of brown-like adipocytes in traditionally white adipose tissue (WAT) depots occurred~30 years ago, but interest in white adipocyte 'browning' only has gained attention more recently. We integrate some of what is known about the sympathetic nervous system (SNS) innervation of WAT and brown adipose tissue (BAT) with the few studies focusing on the sympathetic innervation of the so-called 'brite' or 'beige' adipocytes that appear when WAT sympathetic drive increases (for example, cold exposure and food deprivation). Only one brain site, the dorsomedial hypothalamic nucleus (DMH), selectively browns some (inguinal WAT (IWAT) and dorsomedial subcutaneous WAT), but not all WAT depots and only when DMH neuropeptide Y gene expression is knocked down, a browning effect is mediated by WAT SNS innervation. Other studies show that WAT sympathetic fiber density is correlated with the number of brown-like adipocytes (multilocular lipid droplets, uncoupling protein-1 immunoreactivity) at both warm and cold ambient temperatures. WAT and BAT have sensory innervation, the latter important for acute BAT cold-induced temperature increases, therefore suggesting the possible importance of sensory neural feedback from brite/beige cells for heat production. Only one report shows browned WAT capable of producing heat in vivo. Collectively, increases in WAT sympathetic drive and the phenotype of these stimulated adipocytes seems critical for the production of new and/or transdifferentiation of white to brite/ beige adipocytes. Selective harnessing of WAT SNS drive to produce browning or selective browning independent of the SNS to counter increases in adiposity by increasing expenditure appears to be extremely challenging.

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Knockdown of NPY Expression in the Dorsomedial Hypothalamus Promotes Development of Brown Adipocytes and Prevents Diet-Induced Obesity

Cited by 186 publications

References 51 publications

Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

Neuropeptide Y promotes adipogenic differentiation in primary cultured human adipose-derived stem cells

Neural control of white, beige and brown adipocytes

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