Leptin system loss of function in the absence of obesity in zebrafish

Abstract

The leptin system plays a crucial role in the regulation of appetite and energy homeostasis in vertebrates. While the phenotype of morbid obesity due to leptin or leptin receptor (lepr) loss of function is well established in mammals, evidence in fish is controversial, questioning the role of leptin as the vertebrate adipostat. Here we report on 3 lepr loss of function (lof) and one leptin loss of function allele in zebrafish. In order to demonstrate that the lepr lof alleles cannot transduce a leptin signal, we measured socs3a transcription after intraperitoneal leptin which is abolished by lepr lof. None of the lepr/lepa lof alleles lead to obesity / a body growth phenotype. We explore possible reasons leading to the difference in published results and find that even slight changes in background genetics such as inbreeding siblings and cousins can lead to significant variance in growth.

Probing microstructural changes in muscles of leptin-deficient zebrafish by non-invasive ex-vivo magnetic resonance microimaging

“…With regard to leptin, zebrafish have two major leptin genes: lepa and lepb, and one leptin receptor gene lepr [19,20]. Previously, the obesity phenotype has been observed in a lepa-deficient adult zebrafish [21], however in another study, the obesity phenotype was not consistently observed in lepa or lepr deficient zebrafish [22]. Recently, Kamstra et al have shown that overfeeding elicits elevated body weight in both lepr and lepa deficient zebrafish as compared to control [23].…”