title: Chronic Mild Cold Conditioning Modulates the Expression of Hypothalamic Neuropeptide and Intermediary Metabolic-Related Genes and Improves Growth Performances in Young Chicks.
abstract: BACKGROUND
  Low environmental temperatures are among the most challenging stressors in poultry industries. Although landmark studies using acute severe cold exposure have been conducted, still the molecular mechanisms underlying cold-stress responses in birds are not completely defined. In the present study we determine the effect of chronic mild cold conditioning (CMCC) on growth performances and on the expression of key metabolic-related genes in three metabolically important tissues: brain (main site for feed intake control), liver (main site for lipogenesis) and muscle (main site for thermogenesis).
  
  
  METHODS
  80 one-day old male broiler chicks were divided into two weight-matched groups and maintained in two different temperature floor pen rooms (40 birds/room). The temperature of control room was 32°C, while the cold room temperature started at 26.7°C and gradually reduced every day (1°C/day) to reach 19.7°C at the seventh day of the experiment. At day 7, growth performances were recorded (from all birds) and blood samples and tissues were collected (n = 10). The rest of birds were maintained at the same standard environmental condition for two more weeks and growth performances were measured.
  
  
  RESULTS
  Although feed intake remained unchanged, body weight gain was significantly increased in CMCC compared to the control chicks resulting in a significant low feed conversion ratio (FCR). Circulating cholesterol and creatine kinase levels were higher in CMCC chicks compared to the control group (P<0.05). CMCC significantly decreased the expression of both the hypothalamic orexigenic neuropeptide Y (NPY) and anorexigenic cocaine and amphetamine regulated transcript (CART) in chick brain which may explain the similar feed intake between the two groups. Compared to the control condition, CMCC increased the mRNA abundance of AMPKα1/α2 and decreased mTOR gene expression (P<0.05), the master energy and nutrient sensors, respectively. It also significantly decreased the expression of fatty acid synthase (FAS) gene in chick brain compared to the control. Although their roles are still unknown in avian species, adiponectin (Adpn) and its related receptors (AdipoR1 and 2) were down regulated in the brain of CMCC compared to control chicks (P<0.05). In the liver, CMCC significantly down regulated the expression of lipogenic genes namely FAS, acetyl-CoA carboxylase alpha (ACCα) and malic enzyme (ME) and their related transcription factors sterol regulatory element binding protein 1/2 (SREBP-1 and 2). Hepatic mTOR mRNA levels and phosphorylated mTOR at Ser2448 were down regulated (P<0.05), however phosphorylated ACCαSer79 (inactivation) was up regulated (P<0.05) in CMCC compared to control chicks, indicating that CMCC switch hepatic catabolism on and inhibits hepatic lipogenesis. In the muscle however, CMCC significantly up regulated the expression of carnitine palmitoyltransferase 1 (CPT-1) gene and the mRNA and phosphorylated protein levels of mTOR compared to the control chicks, indicating that CMCC enhanced muscle fatty acid β-oxidation.
  
  
  CONCLUSIONS
  In conclusion, this is the first report indicating that CMCC may regulate AMPK-mTOR expression in a tissue specific manner and identifying AMPK-mTOR as a potential molecular signature that controls cellular fatty acid utilization (inhibition of hepatic lipogenesis and induction of muscle fatty acid β-oxidation) to enhance growth performance during mild cold acclimation.
authors.affiliation: Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR, 72701, United States of America.
authors.forename: Phuong
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR, 72701, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Greene
authors.affiliation: Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR, 72701, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Ishola
authors.affiliation: USDA, Agricultural Research Service, Poultry Production and Product Safety Research Unit, Fayetteville, AR, 72701, United States of America.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Huff
authors.affiliation: USDA, Agricultural Research Service, Poultry Production and Product Safety Research Unit, Fayetteville, AR, 72701, United States of America.
authors.forename: Annie
authors.initials: A
authors.lastname: Donoghue
authors.affiliation: Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR, 72701, United States of America.
authors.forename: Walter
authors.initials: W
authors.lastname: Bottje
authors.affiliation: Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR, 72701, United States of America.
authors.forename: Sami
authors.initials: S
authors.lastname: Dridi
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D002645:Chickens / Q000235:genetics / Q000254:growth & development; D003080:Cold Temperature; D003124:Colorimetry; D005227:Fatty Acids / Q000737:chemistry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism* / Q000502:physiology; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D009479:Neuropeptides; D009841:Oligonucleotides; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase