PUBLICATION

Leptin deficiency affects glucose homeostasis and results in adiposity in zebrafish

Authors
He, J., Ding, Y., Nowik, N., Jager, C., H Eeza, M.N., Alia, A., Baelde, H.J., Spaink, H.P.
ID
ZDB-PUB-210312-12
Date
2021
Source
The Journal of endocrinology   249(2): 125-134 (Journal)
Registered Authors
Nowik, Natalia, Spaink, Herman P.
Keywords
none
MeSH Terms
  • Adiposity/genetics*
  • Adiposity/physiology
  • Animals
  • Blood Glucose
  • Body Weight
  • CRISPR-Cas Systems
  • Gene Deletion
  • Glucose/metabolism*
  • Homeostasis/genetics
  • Homeostasis/physiology*
  • Hypertrophy/etiology
  • Kidney Glomerulus/pathology
  • Leptin/deficiency*
  • Leptin/genetics*
  • Leptin/metabolism
  • Zebrafish
PubMed
33705349 Full text @ J. Endocrinol.
Abstract
Leptin is a hormone which functions in the regulation of energy homeostasis via suppression of appetite. In zebrafish, there are two paralogues genes encoding leptin, called lepa and lepb. In a gene expression study, we found that the lepb gene, not the lepa gene, was significantly downregulated under the state of insulin-resistant in zebrafish larvae, suggesting that the lepb plays a role in insulin homeostasis. In the current study, we characterised lepb-deficient (lepb-/-) adult zebrafish generated via a CRISPR-CAS9 gene editing approach by investigating whether the deletion of lepb gene would result in the development of type 2 diabetes mellitus (T2DM) and diabetic complications. We observed that lepb-/- adult zebrafish had an increase in body weight, length and visceral fat accumulation, compared to age-matched control zebrafish. In addition, lepb-/- zebrafish had significantly higher blood glucose levels compared to control zebrafish. These data collectively indicate that lepb-/- adult zebrafish display the features of T2DM. Furthermore, we showed that lepb-/- adult zebrafish had glomerular hypertrophy and thickening of glomerular basement membrane, compared to control zebrafish, suggesting that lepb-/- adult zebrafish develop early signs of diabetic nephropathy. In conclusion, our results demonstrate that lepb regulates glucose homeostasis and adiposity in zebrafish, and suggest that lepb-/- mutant zebrafish are a promising model to investigate the role of leptin in the development of T2DM and an attractive model to perform mechanistic and therapeutic research in T2DM and its complications.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping