Abstract
Objective:House musk shrew (Suncus murinus), a small experimental animal with low body fat, may be a possible model for human lipodystrophy. Leptin is an adipocyte-derived hormone thought to have an important role in the pathophysiology of lipodystrophy. The objectives of this study were to clarify the structure and distribution of suncus leptin.Materials and methods:To determine the primary structure of suncus leptin, we cloned the suncus Lep cDNA using the rapid amplification of cDNA ends method. The obtained amino acid (aa) sequence was compared with other mammals and the protein structure prediction was performed.Results:The suncus Lep cDNA encodes 170 aa. The putative suncus leptin precursor has a predicted signal peptide of 21 aa, and the mature leptin comprises 149 aa. The mature leptin is 75%–82% homologous to that of other species. Insertion of the three aa, VPQ, not seen in other mammals was found. This VPQ insertion is thought to be due to a nucleotide insertion of nine bases by slippage-like microindels. The predicted 3D structure of suncus leptin exhibited a typical four a-helix structure, however, the VPQ region protruded compared with human leptin. Lep mRNA expression was observed only in white and brown adipose tissues.Conclusion:This study revealed the structure and distribution of suncus leptin. Because the addition of VPQ, which is not found in other mammals, was observed, suncus leptin attracts attention to its physiological action, and to the possibility of being a model of human lipodystrophy.
Highlights
Lipodystrophy syndromes in humans are genetic or acquired disorders in which full or partial deficiency of adipose tissues is seen
Because leptin replacement therapy ameliorates insulin resistance in lipodystrophy [1], the pathophysiological role of leptin associated with insulin resistance development is very interesting
The suncus Lep cDNA sequence was deposited in the DNA Data Bank of Japan (DDBJ) under the accession number LC432494
Summary
Lipodystrophy syndromes in humans are genetic or acquired disorders in which full or partial deficiency of adipose tissues is seen. The adipose tissue deficiency in lipodystrophy is associated with diabetes, insulin resistance, and lipid metabolism disorders including ectopic fat deposition and non-alcoholic fatty liver disease [1]. Shimomura et al [2] have proved that the leptin deficiency caused insulin resistance in transgenic lipodystrophic mice and that leptin replacement remarkably improved insulin sensitivity. Metreleptin, a human recombinant methionyl leptin, has been reported to be effective for leptin replacement therapy for the complications associated with lipodystrophy, and is the only drug approved in the United States and Japan [1]. Leptin replacement remarkably improved the accompanying symptoms seen
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