PUBLICATION

Development of an Assay for High-Throughput Energy Expenditure Monitoring in the Zebrafish

Authors
Renquist, B.J., Zhang, C., Williams, S.Y., and Cone, R.D.
ID
ZDB-PUB-130703-28
Date
2013
Source
Zebrafish   10(3): 343-52 (Journal)
Registered Authors
Cone, Roger, Williams, Savannah
Keywords
none
MeSH Terms
  • Animals
  • Energy Metabolism*
  • Female
  • HEK293 Cells
  • Humans
  • Indicators and Reagents
  • Male
  • Oxazines*
  • Xanthenes*
  • Zebrafish/metabolism*
PubMed
23705823 Full text @ Zebrafish
Abstract

Energy homeostasis is maintained by balancing energy intake and expenditure. Many signals regulating energy intake are conserved between the human and teleost. However, before this work, there was no sensitive high-throughput system to monitor energy expenditure in the teleost. We exploit the nonfluorescent and fluorescent properties of resazurin and its reduced form resorufin (alamarBlue®) to monitor energy expenditure responses to drug application and genetic manipulation. We show that leptin, insulin, and alpha-melanocyte-stimulating hormone (α-MSH) increase energy expenditure dose dependently in the larval zebrafish. As previously established in the mouse, etomoxir, a carnitine palmitoyl transferase I inhibitor, blocks leptin-induced energy expenditure in the zebrafish. Metformin, the most commonly prescribed insulin sensitizer, increases the insulin-induced metabolic rate. Using genetic knockdown, we observed that α-MSH treatment increases the metabolic rate, as does knockdown of the melanocortin antagonist, agouti-related protein. The agouti-related protein and multiple melanocortin receptors are shown to be involved in these effects. These studies confirm that aspects of hormonal regulation of energy expenditure are conserved in the teleost, and suggest that this assay may provide a unique tool to perform in vivo screens for drugs or genes that affect the metabolic rate, including insulin or leptin sensitizers.

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