Structural and functional studies of leptins from hibernating and non-hibernating bats

He, Lin; Pan, Yi-Hsuan; He, Guimei; Lin, Benfu; Liao, Chen Chung; Zuo, Xueguo; Yuan, Lihong

doi:10.1016/j.ygcen.2010.04.001

Cited by 7 publications

(11 citation statements)

References 52 publications

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“…We were able to validate that amino acid substitutions affect the function of heterothermic bat Leptin, by expressing two Leptin proteins of Miniopterus fuliginosus (hibernator) and Rousettus leschenaultii (homeothermy) in E. coli cells and measuring the lipolytic activity assay in vitro . The results of the MTT and LDH assays are consistent and also identical with that of our previous study on Leptin of Rhinolophus ferrumequinum and R. leschenaultii [54]. Our data show that Leptin in heterothermic bats ( M. fuliginosus and R. ferrumequinum ) is more lipolytic than in homeothermic bats, and there is no significant difference between two heterothermic bats.…”

Section: Discussionsupporting

confidence: 91%

Adaptive Evolution of Leptin in Heterothermic Bats

Yuan

Zhao

Lin³

et al. 2011

PLoS ONE

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Heterothermy (hibernation and daily torpor) is a key strategy that animals use to survive in harsh conditions and is widely employed by bats, which are found in diverse habitats and climates. Bats comprise more than 20% of all mammals and although heterothermy occurs in divergent lineages of bats, suggesting it might be an ancestral condition, its evolutionary history is complicated by complex phylogeographic patterns. Here, we use Leptin, which regulates lipid metabolism and is crucial for thermogenesis of hibernators, as molecular marker and combine physiological, molecular and biochemical analyses to explore the possible evolutionary history of heterothermy in bat. The two tropical fruit bats examined here were homeothermic; in contrast, the two tropical insectivorous bats were clearly heterothermic. Molecular evolutionary analyses of the Leptin gene revealed positive selection in the ancestors of all bats, which was maintained or further enhanced the lineages comprising mostly heterothermic species. In contrast, we found evidence of relaxed selection in homeothermic species. Biochemical assays of bat Leptin on the activity on adipocyte degradation revealed that Leptin in heterothermic bats was more lipolytic than in homeothermic bats. This shows that evolutionary sequence changes in this protein are indeed functional and support the interpretation of our physiological results and the molecular evolutionary analyses. Our combined data strongly support the hypothesis that heterothermy is the ancestral state of bats and that this involved adaptive changes in Leptin. Subsequent loss of heterothermy in some tropical lineages of bats likely was associated with range and dietary shifts.

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Section: Discussionsupporting

confidence: 91%

Adaptive Evolution of Leptin in Heterothermic Bats

Yuan

Zhao

Lin³

et al. 2011

PLoS ONE

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“…In order to determine the potential structural and biochemical differences of leptin between hibernating and non-hibernating bats, He et al [100] sequenced the leptin gene of Rhinolophus ferrumequinum (hibernating bat) and Rousettus leschenaultii (non-hibernating bat), and moreover, expressed the leptin proteins from these two bats species in Escherichia coli. Their results demonstrated that there were more amino acid substitutions in hibernating bats leptin than in non-hibernation bats [100].…”

Section: Leptin Evolution and Hibernation Adaptationmentioning

confidence: 99%

“…Their results demonstrated that there were more amino acid substitutions in hibernating bats leptin than in non-hibernation bats [100]. In addition, the structural modeling analysis showed that the receptor binding site III of leptin, which is critical for signal transduction, from hibernating bats, has a helical structure, whereas the same region from non-hibernating bats and human leptin was predicted to be a random loop [26,100].…”

Section: Leptin Evolution and Hibernation Adaptationmentioning

confidence: 99%

“…In addition, the structural modeling analysis showed that the receptor binding site III of leptin, which is critical for signal transduction, from hibernating bats, has a helical structure, whereas the same region from non-hibernating bats and human leptin was predicted to be a random loop [26,100]. The expression assay suggested that hibernating bats leptin reveals a superior inhibitory capacity for growth of 3T3-L1 cells (adipose-like cells) than that of non-hibernating bats [100]. In summary, based on the observation of the differences in amino acid sequence, protein structure, and activity between the leptins of the non-hibernating and hibernating bats, He et al [100] proposed a hypothesis that the hibernating bats leptin may have evolved from the non-hibernating bats leptin and assumed that leptin is likely to play an important role in adipose tissue metabolism of hibernating bats in terms of satisfying the need of special energy supply during the period of torpor [100].…”

Section: Leptin Evolution and Hibernation Adaptationmentioning

confidence: 99%

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Natural selection and adaptive evolution of leptin

Guo

Zhang

2013

Chin. Sci. Bull.

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Leptin is an adiposity-secreted hormone that is pivotal in regulating feeding behavior, energy metabolism and body mass. The study of leptin has been of crucial importance for public health and pharmaceutical intervention given its role in obesity. Generally, leptin is highly conserved due to its functional importance. However, episodes of rapid sequence evolution and positive selection have been observed in some mammalian species, indicating that the leptin functions in these animals may have undergone adaptive modification to their environments. In this article, we review the adaptive evolution of leptin and its potential functional consequences. This review is expected to guide future research of molecular evolution and functional assays of this gene, and also to provide a theoretical foundation for the use of leptin in therapeutic applications. natural selection, adaptive evolution, leptin, leptin receptor Citation:Zou G, Zhang Y P, Yu L. Natural selection and adaptive evolution of leptin. Chin Sci Bull, 2013Bull, , 58: 21042112, doi: 10.1007 The relationship between the adaptations of an organism to different ecological niches with genetic changes (e.g. the change of genes) has been one of the essential subjects in the study of life sciences. Accordingly, the mechanism underlying how organisms adapt to different living environments at molecular level has fascinated evolutionary biologists [1][2][3][4][5][6][7][8][9]. Metabolism is a series of biochemical reactions, allowing organisms to exchange materials and energy with the environment. These processes control growth, reproduction and behavior of organisms. Although the mechanisms of increased energy utilization are likely to be complex, one important component involves the activation of adipose tissue [10].Leptin, encoded by the obese gene, is a hormone that mainly secreted by adipose tissue. It is important in regulating feeding behavior, energy metabolism and body mass [11][12][13][14][15][16]. The level of plasma leptin is generally regarded as a signal to direct the central nervous system (CNS) to regulate food intake and energy expenditure, which is an important pathway of metabolism to maintain constancy of the adipose mass [12,14,17,18]. The mutation of ob gene results in a myriad of disturbance of metabolism [12,19]. Mice that are homozygous (ob/ob mouse) for mutations in this gene exhibit a profound obesity resulting from defects in energy expenditure, food intake and nutrient partitioning [12,20,21]. In humans, mutation of this gene results in a profound obesity and type II diabetes [12,[20][21][22][23]. Therefore, due to its critical role in obesity, the study of leptin will shed insight into molecular mechanism of energy homeostasis, future pharmaceutical intervention and public health [9,10,24].The leptin gene, spanning over 4.5-kb, consists of three exons and two introns [9,25]. The coding exons (exons 2 and 3) are 501 bp in length in total. Leptin contains an amino-terminal signal peptide (21 residues) and a mature peptide (146 residues),...

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“…Exon 3 of lep may be particularly important because it contains 29 amino acid variants with functional significance (Yuan et al, ). Some hibernating bats show structural alterations in exon 3 of lep that may cause leptin to become more physiologically active (He et al, ). Outside of the relationship leptin has with food intake and temperature regulation, leptin has a mechanistically independent function in initiating torpor bouts in some species (Stehling, Doring, & Ertl, ; Swoap, ).…”

Section: Introductionmentioning

confidence: 99%

Hibernation in bats (Mammalia: Chiroptera) did not evolve through positive selection of leptin

Lazzeroni

Burbrink

Simmons

2018

Ecology and Evolution

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Temperature regulation is an indispensable physiological activity critical for animal survival. However, relatively little is known about the origin of thermoregulatory regimes in a phylogenetic context, or the genetic mechanisms driving the evolution of these regimes. Using bats as a study system, we examined the evolution of three thermoregulatory regimes (hibernation, daily heterothermy, and homeothermy) in relation to the evolution of leptin, a protein implicated in regulation of torpor bouts in mammals, including bats. A threshold model was used to test for a correlation between lineages with positively selected lep, the gene encoding leptin, and the thermoregulatory regimes of those lineages. Although evidence for episodic positive selection of lep was found, positive selection was not correlated with lineages of heterothermic bats, a finding that contradicts results from previous studies. Evidence from our ancestral state reconstructions suggests that the most recent common ancestor of bats used daily heterothermy and that the presence of hibernation is highly unlikely at this node. Hibernation likely evolved independently at least four times in bats—once in the common ancestor of Vespertilionidae and Molossidae, once in the clade containing Rhinolophidae and Rhinopomatidae, and again independently in the lineages leading to Taphozous melanopogon and Mystacina tuberculata. Our reconstructions revealed that thermoregulatory regimes never transitioned directly from hibernation to homeothermy, or the reverse, in the evolutionary history of bats. This, in addition to recent evidence that heterothermy is best described along a continuum, suggests that thermoregulatory regimes in mammals are best represented as an ordered continuous trait (homeothermy ← → daily torpor ← → hibernation) rather than as the three discrete regimes that evolve in an unordered fashion. These results have important implications for methodological approaches in future physiological and evolutionary research.

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Structural and functional studies of leptins from hibernating and non-hibernating bats

Cited by 7 publications

References 52 publications

Adaptive Evolution of Leptin in Heterothermic Bats

Adaptive Evolution of Leptin in Heterothermic Bats

Natural selection and adaptive evolution of leptin

Hibernation in bats (Mammalia: Chiroptera) did not evolve through positive selection of leptin

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