Identification of the Long-Sought Leptin in Chicken and Duck: Expression Pattern of the Highly GC-Rich Avian leptin Fits an Autocrine/Paracrine Rather Than Endocrine Function

Abstract

More than 20 years after characterization of the key regulator of mammalian energy balance, leptin, we identified the leptin (LEP) genes of chicken (Gallus gallus) and duck (Anas platyrhynchos). The extreme guanine-cytosine content (∼70%), the location in a genomic region with low-complexity repetitive and palindromic sequence elements, the relatively low sequence conservation, and low level of expression have hampered the identification of these genes until now. In vitro-expressed chicken and duck leptins specifically activated signaling through the chicken leptin receptor in cell culture. In situ hybridization demonstrated expression of LEP mRNA in granular and Purkinje cells of the cerebellum, anterior pituitary, and in embryonic limb buds, somites, and branchial arches, suggesting roles in adult brain control of energy balance and during embryonic development. The expression patterns of LEP and the leptin receptor (LEPR) were explored in chicken, duck, and quail (Coturnix japonica) using RNA-sequencing experiments available in the Short Read Archive and by quantitative RT-PCR. In adipose tissue, LEP and LEPR were scarcely transcribed, and the expression level was not correlated to adiposity. Our identification of the leptin genes in chicken and duck genomes resolves a long lasting controversy regarding the existence of leptin genes in these species. This identification was confirmed by sequence and structural similarity, conserved exon-intron boundaries, detection in numerous genomic, and transcriptomic datasets and characterization by PCR, quantitative RT-PCR, in situ hybridization, and bioassays. Our results point to an autocrine/paracrine mode of action for bird leptin instead of being a circulating hormone as in mammals.

Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster

“…The possibility remains that other such dark DNA regions could be widespread features of animal genomes, thus far largely overlooked in comparative animal genomics. Indeed, GC-rich genes are also missing from the chicken genome assembly (28,29). Hotspots of mutation could drive rapid evolutionary change at the molecular level, and it will be important to decipher to what extent such hotspots have constrained and influenced evolutionary adaptation across the animal kingdom.…”

Neuropeptide Control of Feeding Behavior in Birds and Its Difference with Mammals

“…Recently, the leptin gene has been isolated in several kinds of birds (Boswell and Dunn, 2015). The chicken leptin gene has also been newly identified (Seroussi et al, 2016). Avian leptin exhibits ~30% amino acid identity to its mouse and human counterparts (Boswell and Dunn, 2015).…”

Gut Hormones and Regulation of Food Intake in Birds

“…However, there is much debate on the physiological significance of leptin and insulin as adiposity hormones in birds. For example, the mRNA levels of leptin in adipose tissue were extremely low in chickens (Seroussi et al, 2016), zebra finches (Huang et al, 2014), and rock doves (Friedman-Einat et al, 2014) and relatively low in Japanese quail (Seroussi et al, 2016). Plasma insulin levels were not correlated with either abdominal fat mass or the mRNA levels of appetite-regulating neuropeptides in the hypothalamus in layer chickens (Honda et al, 2015a).…”