Thermogenic activity of UCP1 in human white fat-derived beige adipocytes

Mol Endocrinol. 2015 Jan;29(1):130-9. doi: 10.1210/me.2014-1295.

Abstract

Heat-producing beige/brite (brown-in-white) adipocytes in white adipose tissue have the potential to suppress metabolic disease in mice and hold great promise for the treatment of obesity and type 2 diabetes in humans. Here, we demonstrate that human adipose-derived stromal/progenitor cells (hASCs) from subcutaneous white adipose tissue can be efficiently converted into beige adipocytes. Upon pharmacological activation of peroxisome proliferator-activated receptor-γ, hASC-derived adipocytes activated beige fat-selective genes and a brown/beige fat-selective electron transport chain gene program. Importantly, hASC-derived beige fat cells displayed the bioenergetic characteristics of genuine brown fat cells, including a capacity for increased respiratory uncoupling in response to β-adrenergic agonists. Furthermore, knock-down experiments reveal that the thermogenic capacity of human beige fat cells was entirely dependent on the presence of Uncoupling protein 1. In summary, this study reveals that hASCs can be readily differentiated into beige adipocytes that, upon activation, undergo uncoupling protein 1-dependent thermogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / cytology*
  • Adipocytes, White / metabolism*
  • Adipose Tissue, White / cytology
  • Cell Differentiation
  • Cells, Cultured
  • Electron Transport / genetics
  • Electron Transport / physiology
  • Electron Transport Chain Complex Proteins / genetics
  • Energy Metabolism / physiology*
  • Enzyme Activation
  • Humans
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Mesenchymal Stem Cells / cytology
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Oxygen / metabolism
  • Oxygen Consumption / physiology
  • PPAR gamma / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Thermogenesis / physiology*
  • Uncoupling Protein 1

Substances

  • Electron Transport Chain Complex Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • PPAR gamma
  • RNA, Small Interfering
  • UCP1 protein, human
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Oxygen

Grant support

This work was supported by the AstraZeneca postdoc program (S.B.).