Lipids

, Volume 50, Issue 2, pp 111–120 | Cite as

BMP7 Drives Human Adipogenic Stem Cells into Metabolically Active Beige Adipocytes

  • Meshail Okla
  • Jung-Heun Ha
  • Ryan E. Temel
  • Soonkyu Chung
Original Article

Abstract

Adult humans have a substantial amount of inducible-brown (or beige) fat, which is associated with increased energy expenditure and reduced weight gain via thermogenesis. Despite the identification of key regulators of beige adipogenesis, impacts of dietary factors on adaptive thermogenesis are largely unknown, partly due to a lack of validated human cell models. Bone morphogenetic protein 7 (BMP7) is known to promote brown adipogenesis in rodent and human progenitor cells. However, controversy still surrounds the cellular identity in BMP7-mediated transition of white to brown adipocytes. The aim of this study was to confirm BMP7-derived human adipocytes as a relevant in vitro model of human beige adipocyte by verifying the cellular lineage and metabolic activity. In this study, we hypothesized that pre-exposure of the stromal vascular (SV) fraction of primary human adipogenic precursor cells (hASC) to BMP7 would convert metabolically active brown adipocytes. Our results showed that exposure of hASC to human BMP7 was associated with significant escalation of (1) UCP1 gene expression, a signature gene of brown adipocytes, (2) beige specific marker gene expression (i.e., CD137 and TMEM26), (3) glucose and fatty acid uptake, and (4) basal and cAMP-stimulated oxygen consumption rate compared to white adipocyte control. Taken together, we demonstrated that BMP7 mediates conversion of hASC into metabolically active beige adipocytes. By confirming the cellular identity and metabolic activity, this BMP7-induced human beige adipocytes from hASC should aid in the discovery and assessment of bioactive molecules to promote adaptive thermogenesis.

Keywords

Brown adipose tissue Beige adipogenesis Bone morphogenetic protein 7 UCP1 Human adipose-derived stem cells 

Abbreviation

AA

Antimycin A

ADRB3

Β3-Adrenoceptor

ASC

Adipogenic stem cells

BAT

Brown adipose tissue

BDNF

Brain derived neurotrophic factor

BRL

Rosiglitazone

BMP7

Bone morphogenetic protein 7

Bt2-cAMP

8-Bromo cyclic AMP

CD137

Cluster of differentiation 137

CIDEA

Cell-death inducing DFF45-like effector A

FGF21

Fibroblast growth factor 21

FNDC5

Fibronectin type III domain containing 5 (precursor of Irisin)

GLUT4

Glucose transporter 4

OLA

Oleic acid

PPARγ

Peroxisome proliferator-activated receptor gamma

PRDM16

PR domain containing 16

SubQ

Subcutaneous fat

SV

Stromal vascular

TAG

Triacylglycerol

TMEM26

Transmembrane protein 26

UCP1

Uncoupling protein 1

WAT

White adipose tissue

Notes

Acknowledgments

This work was supported in part by grants from the NIH-NCRR to SC (1UL1RR029890), the NIH-1P20GM104320 (Project 5) to SC, and a NIH-NHLBI grant to RET (R00HL088528).

Conflict of interest

None.

Supplementary material

11745_2014_3981_MOESM1_ESM.docx (865 kb)
Supplementary material 1 (DOCX 864 kb)

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Copyright information

© AOCS 2014

Authors and Affiliations

  • Meshail Okla
    • 1
    • 2
  • Jung-Heun Ha
    • 2
  • Ryan E. Temel
    • 3
    • 4
  • Soonkyu Chung
    • 1
    • 2
  1. 1.Department of Nutrition and Health SciencesUniversity of NebraskaLincolnUSA
  2. 2.Department of Food Science and Human NutritionUniversity of FloridaGainesvilleUSA
  3. 3.Section on Lipid Sciences, Department of PathologyWake Forest University Health SciencesWinston-SalemUSA
  4. 4.Department of Pharmacology and Nutritional Sciences, Saha Cardiovascular Research CenterUniversity of KentuckyLexingtonUSA

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