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

Endocr J. 2018 Jan 30;65(1):43-52. doi: 10.1507/endocrj.EJ17-0017. Epub 2017 Sep 28.

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.

Keywords: Adipocyte differentiation; Human adipose-derived stem cells; Neuropeptide Y; White adipose tissue.

MeSH terms

  • Abdominal Fat / metabolism*
  • Abdominal Fat / pathology
  • Abdominal Fat / surgery
  • Adaptor Proteins, Signal Transducing / agonists
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adipogenesis*
  • Adult
  • Adult Stem Cells / metabolism*
  • Adult Stem Cells / pathology
  • Apoptosis Regulatory Proteins
  • Biomarkers / metabolism
  • CCAAT-Enhancer-Binding Proteins / agonists*
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Elective Surgical Procedures
  • Female
  • Gene Expression Regulation, Developmental*
  • Humans
  • Lipid Droplets / metabolism
  • Lipid Metabolism
  • Neuropeptide Y / metabolism*
  • Nuclear Proteins / agonists
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Interacting Protein 1
  • Osmolar Concentration
  • Overweight / metabolism
  • Overweight / pathology
  • PPAR gamma / agonists*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Proteins / agonists
  • Proteins / metabolism
  • Receptors, Neuropeptide Y / agonists
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Biomarkers
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • CIDEC protein, human
  • NRIP1 protein, human
  • Neuropeptide Y
  • Nuclear Proteins
  • Nuclear Receptor Interacting Protein 1
  • PPAR gamma
  • Proteins
  • Receptors, Neuropeptide Y
  • neuropeptide Y2 receptor
  • neuropeptide Y5 receptor