title: Functional evolution of leptin of Ochotona curzoniae in adaptive thermogenesis driven by cold environmental stress.
abstract: BACKGROUND
  Environmental stress can accelerate the directional selection and evolutionary rate of specific stress-response proteins to bring about new or altered functions, enhancing an organism's fitness to challenging environments. Plateau pika (Ochotona curzoniae), an endemic and keystone species on Qinghai-Tibetan Plateau, is a high hypoxia and low temperature tolerant mammal with high resting metabolic rate and non-shivering thermogenesis to cope in this harsh plateau environment. Leptin is a key hormone related to how these animals regulate energy homeostasis. Previous molecular evolutionary analysis helped to generate the hypothesis that adaptive evolution of plateau pika leptin may be driven by cold stress.
  
  
  RESULTS
  To test the hypothesis, recombinant pika leptin was first purified. The thermogenic characteristics of C57BL/6J mice injected with pika leptin under warm (23±1°C) and cold (5±1°C) acclimation is investigated. Expression levels of genes regulating adaptive thermogenesis in brown adipose tissue and the hypothalamus are compared between pika leptin and human leptin treatment, suggesting that pika leptin has adaptively and functionally evolved. Our results show that pika leptin regulates energy homeostasis via reduced food intake and increased energy expenditure under both warm and cold conditions. Compared with human leptin, pika leptin demonstrates a superior induced capacity for adaptive thermogenesis, which is reflected in a more enhanced β-oxidation, mitochondrial biogenesis and heat production. Moreover, leptin treatment combined with cold stimulation has a significant synergistic effect on adaptive thermogenesis, more so than is observed with a single cold exposure or single leptin treatment.
  
  
  CONCLUSIONS
  These findings support the hypothesis that cold stress has driven the functional evolution of plateau pika leptin as an ecological adaptation to the Qinghai-Tibetan Plateau.
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Bromage
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Bao Hong
authors.initials: BH
authors.lastname: Xu
authors.forename: Wei Li
authors.initials: WL
authors.lastname: Gao
authors.forename: Hui Fang
authors.initials: HF
authors.lastname: Tian
authors.forename: Hui Jun
authors.initials: HJ
authors.lastname: Tang
authors.forename: Dian Wu
authors.initials: DW
authors.lastname: Liu
authors.forename: Xin Quan
authors.initials: XQ
authors.lastname: Zhao
mesh_terms: D000222:Adaptation, Physiological; D002001:Adipose Tissue, Brown / Q000502:physiology; D000818:Animals; D001833:Body Temperature Regulation; D003080:Cold Temperature; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D007793:Lagomorpha / Q000502:physiology*; D020738:Leptin / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D020738:Leptin