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

Abstract

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...

Neuropeptide Y Promotes Human M2 Macrophage Polarization and Enhances p62/SQSTM1-Dependent Autophagy and NRF2 Activation

“…The NPY is reported to possess bimodal features. Accordingly, its biological action has been described not only in a concentration-dependent fashion [ 51 ], but also associated to the relative affinity with its receptors in the microenvironment [ 52 , 53 ]. The NPY-enhanced endocytosis result is in line with the increased expression of the endocytic receptor CD206 observed in NPY-stimulated macrophages, thus indicating the activation toward an M2-like phenotype.…”

Platelet Lysate-Derived Neuropeptide y Influences Migration and Angiogenesis of Human Adipose Tissue-Derived Stromal Cells

“…The NPY is reported to possess bimodal features. Accordingly, its biological action has been described not only in a concentration-dependent fashion 51 but also associated to the relative affinity with its receptors in the microenvironment 17 , 34 . Higher concentrations of NPY have been reported to neither increase cell proliferation, nor adipocytes differentiation and migration in wound scratch in vitro assays 52 , 53 .…”

Regulation of neuropeptide Y in body microenvironments and its potential application in therapies: a review

“…Alternatively, there are few studies on NPY and adipose-derived stem cells (ADSCs), but it has still been shown that Y2R and Y5R are expressed in human ADSCs, and NPY may play a role in human ADSC proliferation and adipogenic differentiation by interacting with these two receptors [ 138 ]. Liu et al established a model of human ADSCs from human adipose tissue and differentiated them into adipocytes at different concentrations of NPY to determine the effects of different NPY doses on proliferation and adipogenic differentiation [ 138 ]. In their study, low-dose NPY treatment promoted the proliferation of human ADSCs, while high-dose treatment inhibited it.…”

“…In their study, low-dose NPY treatment promoted the proliferation of human ADSCs, while high-dose treatment inhibited it. NPY significantly promoted lipid accumulation, increased the size of lipid droplets, and increased the levels of adipocyte markers PPAR-γ and C/EBPα [ 138 ]. In conclusion, the prospective applications of NPY treatment of stem cells are promising.…”