Effects of Exogenous Glucocorticoid Infusion on Appetitic Center Development in Postnatal Dairy Bull Calves

Simple Summary The profitability of production systems for livestock is directly impacted by body weight, which is influenced by an individual animal’s hypothalamic regulation of food intake. The objective of this study was to determine the effects of exogenous cortisol administration on circulating leptin concentrations, protein expression in various fat depots, and the hypothalamic expression of genes associated with appetite regulation in Holstein bull calves. Within 4 h of parturition, Holstein bull calves (9/treatment) were intravenously infused with either a low (3.5 µg/kg of body weight (BW)) or high (7.0 µg/kg of BW) dose of cortisol or a sham infusion control (with a similar volume of saline). At five days of age, blood, cerebrospinal fluid from the third ventricle of the brain, and adipose (omental, perirenal, and mesenteric) and hypothalamic tissue were collected for the analysis of proteins and genes associated with appetite regulation. Exogenous cortisol administered to perinatal dairy bull calves reduced leptin concentrations in serum and cerebrospinal fluid, decreased the protein expression of leptin in perirenal and omental adipose tissue, and altered gene expression in hypothalamic tissue. Further investigation is necessary to determine if glucocorticoid administration can be utilized as a tool to improve feed intake in cattle later on in life due to hypothalamic programming at birth. Abstract The objective of this study was to determine the effects of exogenous glucocorticoid administration on leptin concentrations and brain development markers, such as protein and hypothalamic gene expression, in dairy bull calves. Within 4 h of parturition, Holstein bulls were intravenously infused with either a low cortisol dose (LC; n = 9, 3.5 µg/kg of body weight (BW)), high cortisol dose (HC; n = 9, 7.0 µg/kg BW), or control (CON; n = 9, saline) dose, with a 2nd infusion 24 h postpartum. Jugular blood was collected prior to infusion and daily until the calves were euthanized (day 5). Cerebrospinal fluid (CSF) from the third ventricle and adipose (omental, perirenal, and mesenteric) and hypothalamic tissue were collected. The blood and CSF samples were analyzed for leptin concentrations. The data were analyzed using SAS. Serum (p = 0.013) and CSF (p = 0.005) leptin concentrations in HC- and LC-treated calves were decreased compared with CON-treated calves. Leptin protein expression was decreased (p < 0.044) in perirenal and omental adipose tissue of LC-treated calves compared with CON-treated calves. Gene abundance of brain-derived neurotrophic factor and fibroblast growth factors 1 and 2 were decreased (p < 0.006) in HC- and LC-treated calves compared with CON-treated calves. In summary, cortisol administered to dairy bull calves reduced leptin concentrations, decreased leptin protein expression in perirenal and omental adipose tissue, and altered gene expression in hypothalamic tissue.

[1]  D. Mota-Rojas,et al.  Parturition in Mammals: Animal Models, Pain and Distress , 2021, Animals : an open access journal from MDPI.

[2]  D. Thivel,et al.  Leptin as a Biomarker of Stress: A Systematic Review and Meta-Analysis , 2021, Nutrients.

[3]  N. Long,et al.  Short communication: Manipulation of neonatal leptin profile via exogenous glucocorticoids in beef calves. , 2019, Animal : an international journal of animal bioscience.

[4]  M. A. Abd El-Hack,et al.  Stress biomarkers and proteomics alteration to thermal stress in ruminants: A review. , 2019, Journal of thermal biology.

[5]  N. Long,et al.  The effects of late gestation nutrient restriction of dams on beef heifer intake, metabolites and hormones during an ad libitum feeding trial , 2018, Journal of animal physiology and animal nutrition.

[6]  D. Zieba,et al.  Phenomenon of leptin resistance in seasonal animals: the failure of leptin action in the brain. , 2015, Domestic animal endocrinology.

[7]  P. Nathanielsz,et al.  Maternal Obesity in Sheep Increases Fatty Acid Synthesis, Upregulates Nutrient Transporters, and Increases Adiposity in Adult Male Offspring after a Feeding Challenge , 2015, PloS one.

[8]  P. Nathanielsz,et al.  Multi-generational Impact of Maternal Overnutrition/Obesity in the Sheep on the Neonatal Leptin Surge in Granddaughters , 2014, International Journal of Obesity.

[9]  S. Blackshaw,et al.  Feed your head: neurodevelopmental control of feeding and metabolism. , 2014, Annual review of physiology.

[10]  N. Long,et al.  Sex effects on plasma leptin concentrations in newborn and postnatal beef calves , 2013 .

[11]  P. Nathanielsz,et al.  Elevated glucocorticoids during ovine pregnancy increase appetite and produce glucose dysregulation and adiposity in their granddaughters in response to ad libitum feeding at 1 year of age. , 2013, American journal of obstetrics and gynecology.

[12]  T. Numakawa,et al.  Brain-derived neurotrophic factor and glucocorticoids: Reciprocal influence on the central nervous system , 2013, Neuroscience.

[13]  T. Numakawa,et al.  Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex , 2012, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[14]  K. Blennow,et al.  Plasma BDNF Levels Vary in Relation to Body Weight in Females , 2012, PloS one.

[15]  Mei J. Zhu,et al.  Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots. , 2012, Journal of animal science.

[16]  T. Numakawa,et al.  Glucocorticoid suppresses BDNF‐stimulated MAPK/ERK pathway via inhibiting interaction of Shp2 with TrkB , 2011, FEBS letters.

[17]  P. Nathanielsz,et al.  Maternal obesity eliminates the neonatal lamb plasma leptin peak , 2011, The Journal of physiology.

[18]  J. Buitelaar,et al.  Determinants of serum brain-derived neurotrophic factor , 2011, Psychoneuroendocrinology.

[19]  A. B. Uthlaut,et al.  Maternal obesity and increased nutrient intake before and during gestation in the ewe results in altered growth, adiposity, and glucose tolerance in adult offspring. , 2010, Journal of animal science.

[20]  N. Karrow,et al.  Endotoxin exposure during late pregnancy alters ovine offspring febrile and hypothalamic–pituitary–adrenal axis responsiveness later in life , 2010, Stress.

[21]  C. Adam,et al.  Decreased blood–brain leptin transfer in an ovine model of obesity and weight loss: resolving the cause of leptin resistance , 2010, International Journal of Obesity.

[22]  P. Taylor,et al.  Maternal Obesity Induced by Diet in Rats Permanently Influences Central Processes Regulating Food Intake in Offspring , 2009, PloS one.

[23]  T. Numakawa,et al.  Glucocorticoid receptor interaction with TrkB promotes BDNF-triggered PLC-γ signaling for glutamate release via a glutamate transporter , 2009, Proceedings of the National Academy of Sciences.

[24]  D. Sloboda,et al.  Expression of glucocorticoid receptor, mineralocorticoid receptor, and 11beta-hydroxysteroid dehydrogenase 1 and 2 in the fetal and postnatal ovine hippocampus: ontogeny and effects of prenatal glucocorticoid exposure. , 2008, The Journal of endocrinology.

[25]  P. Gluckman,et al.  The effect of neonatal leptin treatment on postnatal weight gain in male rats is dependent on maternal nutritional status during pregnancy. , 2008, Endocrinology.

[26]  J. Lesage,et al.  Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of arcuate nucleus proopiomelanocortin neurons in neonatal male rat pups. , 2008, Endocrinology.

[27]  H. Münzberg,et al.  Differential accessibility of circulating leptin to individual hypothalamic sites. , 2007, Endocrinology.

[28]  R B Simerly,et al.  Developmental programming of hypothalamic feeding circuits , 2006, Clinical genetics.

[29]  S. Ozanne,et al.  Programming of appetite and type 2 diabetes. , 2005, Early human development.

[30]  A. Fowden,et al.  Endocrine and metabolic programming during intrauterine development. , 2005, Early human development.

[31]  K. Nakao,et al.  Role of premature leptin surge in obesity resulting from intrauterine undernutrition. , 2005, Cell metabolism.

[32]  Jeffrey S. Robinson,et al.  Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. , 2005, Physiological reviews.

[33]  H. Hammon,et al.  Plasma leptin status in young calves: effects of pre-term birth, age, glucocorticoid status, suckling, and feeding with an automatic feeder or by bucket. , 2005, Domestic animal endocrinology.

[34]  H. Scharfman,et al.  Brain-derived neurotrophic factor. , 2004, Growth factors.

[35]  K. Eguchi,et al.  Rapid Inhibition of Leptin Signaling by Glucocorticoids in Vitro and in Vivo* , 2004, Journal of Biological Chemistry.

[36]  M. Pfaffl,et al.  Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper – Excel-based tool using pair-wise correlations , 2004, Biotechnology Letters.

[37]  D. Keisler,et al.  Maternal endocrine adaptation throughout pregnancy to nutritional manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development. , 2003, Endocrinology.

[38]  P. Chelikani,et al.  Short communication: Tissue distribution of leptin and leptin receptor mRNA in the bovine. , 2003, Journal of dairy science.

[39]  Paul Hawkins,et al.  A Periconceptional Nutritional Origin for Noninfectious Preterm Birth , 2003, Science.

[40]  G. Horgan,et al.  Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR , 2002 .

[41]  W. Banks,et al.  Characterizaton of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity. , 2002, Endocrinology.

[42]  A. Benraiss,et al.  Adenoviral Brain-Derived Neurotrophic Factor Induces Both Neostriatal and Olfactory Neuronal Recruitment from Endogenous Progenitor Cells in the Adult Forebrain , 2001, The Journal of Neuroscience.

[43]  G. Frühbeck.  A heliocentric view of leptin , 2001, Proceedings of the Nutrition Society.

[44]  R. Ahima,et al.  Adipose Tissue as an Endocrine Organ , 2006, Obesity.

[45]  Y. Uezono,et al.  Characterization and functional role of leptin receptor in bovine adrenal medullary cells. , 2000, Biochemical pharmacology.

[46]  S. Woods,et al.  Central nervous system control of food intake , 2000, Nature.

[47]  J. Halaas,et al.  Leptin and the regulation of body weight in mammals , 1998, Nature.

[48]  Stanley J. Wiegand,et al.  Intraventricular Administration of BDNF Increases the Number of Newly Generated Neurons in the Adult Olfactory Bulb , 1998, Molecular and Cellular Neuroscience.

[49]  L. Tartaglia,et al.  The Leptin Receptor* , 1997, The Journal of Biological Chemistry.

[50]  J. Seckl,et al.  Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. , 1996, Neuroendocrinology.

[51]  R. Considine,et al.  Serum immunoreactive-leptin concentrations in normal-weight and obese humans. , 1996, The New England journal of medicine.

[52]  B. Lowell,et al.  Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action , 1995, Nature Medicine.

[53]  E. Ravussin,et al.  Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects , 1995, Nature Medicine.

[54]  F. Lönnqvist,et al.  Overexpression of the obese (ob) gene in adipose tissue of human obese subjects , 1995, Nature Medicine.

[55]  M. Deitel,et al.  Increased obese mRNA expression in omental fat cells from massively obese humans , 1995, Nature Medicine.

[56]  G. Yancopoulos,et al.  A BDNF autocrine loop in adult sensory neurons prevents cell death , 1995, Nature.

[57]  Y. Barde,et al.  Brain-derived neurotrophic factor prevents neuronal death in vivo , 1988, Nature.

[58]  N. Ling,et al.  Isolation and partial characterization of an endothelial cell growth factor from the bovine kidney: homology with basic fibroblast growth factor , 1985, Regulatory Peptides.

[59]  R. Lobb,et al.  Purification of two distinct growth factors from bovine neural tissue by heparin affinity chromatography. , 1984, Biochemistry.

[60]  N. Ling,et al.  Isolation and partial molecular characterization of pituitary fibroblast growth factor. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[61]  J. Longenecker,et al.  Glucocorticoid influence on growth of vascular wall cells in culture , 1982, Journal of cellular physiology.

[62]  D. Gospodarowicz,et al.  Stimulation of division of Y1 adrenal cells by a growth factor isolated from bovine pituitary glands. , 1975, Endocrinology.

[63]  D. Gospodarowicz.  Purification of a fibroblast growth factor from bovine pituitary. , 1975, The Journal of biological chemistry.

[64]  D. Gospodarowicz.  Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth , 1974, Nature.

[65]  G. Liggins,et al.  Premature delivery of foetal lambs infused with glucocorticoids. , 1969, The Journal of endocrinology.

[66]  N. Long,et al.  The effects of late gestation maternal nutrient restriction with or without protein supplementation on endocrine regulation of newborn and postnatal beef calves. , 2017, Theriogenology.

[67]  E. Huang,et al.  Neurotrophins: roles in neuronal development and function. , 2001, Annual review of neuroscience.

[68]  K. Houseknecht,et al.  Growth hormone regulates leptin gene expression in bovine adipose tissue: correlation with adipose IGF-1 expression. , 2000, The Journal of endocrinology.

[69]  M. Spurlock,et al.  Partial cloning and expression of the bovine leptin gene. , 1998, Animal biotechnology.

[70]  K. Thomas,et al.  Purification and characterization of acidic fibroblast growth factor from bovine brain. , 1984, Proceedings of the National Academy of Sciences of the United States of America.