NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism

Seongjoon Park, Chika Fujishita, Toshimitsu Komatsu, Sang Eun Kim, Takuya Chiba, Ryoichi Mori, Isao Shimokawa

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

Original languageEnglish
Pages (from-to)5337-5348
Number of pages12
JournalFASEB Journal
Volume28
Issue number12
DOIs
Publication statusPublished - 2014 Dec 1

Fingerprint

Neuropeptide Y
Adiposity
Metabolism
Adipose Tissue
Tissue
White Adipose Tissue
Lipogenesis
Cyclic AMP Response Element-Binding Protein
Lipolysis
Lipid Metabolism
3T3-L1 Cells
Appetite Regulation
Adipogenesis
Peroxisome Proliferator-Activated Receptors
Groin
Thermogenesis
Metabolic Diseases
Gene expression
Knockout Mice
Proteins

Keywords

  • Adipocytes
  • Lipid metabolism
  • Sirtuins

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Park, S., Fujishita, C., Komatsu, T., Kim, S. E., Chiba, T., Mori, R., & Shimokawa, I. (2014). NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism. FASEB Journal, 28(12), 5337-5348. https://doi.org/10.1096/fj.14-258384

NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism. / Park, Seongjoon; Fujishita, Chika; Komatsu, Toshimitsu; Kim, Sang Eun; Chiba, Takuya; Mori, Ryoichi; Shimokawa, Isao.

In: FASEB Journal, Vol. 28, No. 12, 01.12.2014, p. 5337-5348.

Research output: Contribution to journalArticle

Park, S, Fujishita, C, Komatsu, T, Kim, SE, Chiba, T, Mori, R & Shimokawa, I 2014, 'NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism', FASEB Journal, vol. 28, no. 12, pp. 5337-5348. https://doi.org/10.1096/fj.14-258384
Park, Seongjoon ; Fujishita, Chika ; Komatsu, Toshimitsu ; Kim, Sang Eun ; Chiba, Takuya ; Mori, Ryoichi ; Shimokawa, Isao. / NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism. In: FASEB Journal. 2014 ; Vol. 28, No. 12. pp. 5337-5348.
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