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
-
- Zebrafish
- Homeostasis/genetics
- Homeostasis/physiology*
- Adiposity/genetics*
- Adiposity/physiology
- Kidney Glomerulus/pathology
- Blood Glucose
- CRISPR-Cas Systems
- Animals
- Body Weight
- Gene Deletion
- Hypertrophy/etiology
- Leptin/deficiency*
- Leptin/genetics*
- Leptin/metabolism
- Glucose/metabolism*
- PubMed
- 33705349 Full text @ J. Endocrinol.
Citation
He, J., Ding, Y., Nowik, N., Jager, C., H Eeza, M.N., Alia, A., Baelde, H.J., Spaink, H.P. (2021) Leptin deficiency affects glucose homeostasis and results in adiposity in zebrafish. The Journal of endocrinology. 249(2):125-134.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping