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Neonatal
Thermoregulation
Lucille Little
ANS 526: Perinatology
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Early life is difficult for the piglet
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“Please imagine, gentle reader, that you suddenly find yourself beside a
recumbent elephant in a small, locked room. The elephant seems
agitated; she periodically jumps to her feet and then crashes to the
floor, and may even whirl about and attack you without warning.
Unfortunately, you entered the room by being squeezed through a
narrow tube and perhaps partly suffocated, so that you are none too
steady on your feet. You ought to keep far from the elephant as the
limited space permits, but you cannot afford this luxury because you are
cold, wet, unclothed, and desperately short of food; and the only source
of food is the elephant’s milk. Competing for this resource, however, are
10 or more individuals like yourself, some of them twice your body
weight, and murderously aggressive and armed with sharp teeth.”
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Introduction statement in “Behavioural perspectives on piglet survival”
by D. Fraser 1990.
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No Need In Utero
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A developing fetus has
little need to produce
its own
thermoregulation
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Transfer of heat from
placenta and mother’s
uterus
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Differences Among Species
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Humans and ruminants are known to primarily use nonshivering thermogenesis via the use of brown adipose tissue.
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Conversely, pigs completely lack brown adipose tissue:
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rely almost exclusively on shivering mechanisms to regulate
temperature (Berthon et al. 19994)
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Thermoregulation
Thermoregulation: process by which the body is able to
maintain its core internal temperature
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Remaining within the thermo-neutral (TN) zone is paramount
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Two methods:
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Shivering thermogenesis
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Non-shivering thermogenesis
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Shivering Thermogenesis
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Physiological response to hypothermia
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Skeletal muscles begin to contract
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Creating warmth via energy expenditure
Dependent upon glycogen stores and cardiovascular fitness
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Shivering Thermogenesis Cont.
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Premature or relatively small neonates have an exceptionally
large skin surface area compared to body mass
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This results in proportionately more heat loss through skin
than adults (Knobel et al. 2010)
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Decrease in temp below
resting metabolic rate
results in increased
metabolism for
maintenance of homeostasis
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A Difficult Dichotomy
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A sow is most comfortable at ~70°F
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Ideal environment for a piglet is 90-95°F
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Lower critical temperature is ~84°F
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Thermoregulation of Piglets
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Due to the lack of BAT in piglets, rate of thermogenesis is
dictated by the amount of stored glycogen
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Ingestion of colostrum Increased metabolic rate
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There is a direct correlation between heat production and
colostrum intake
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Colostrum Intake & Thermoregulation
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Dividich et al. observed colostrum intake in two different
groups of pigs.
 18-20°C (CG=Cold Group) & 30-32°C (WG=Warm Group)
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CG pigs consumed 38.1% less colostrum (P<0.01)
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Positive correlation between birth weight and colostrum
intake
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Colostrum intake could be effectively measured from birth
weight (R2=.75)
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5 of 39 (12.8%) from CG group died within 3 days postpartum
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0 of 41 from WG died within 3 days post-partum
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Metabolic Affects of Sustained 48-hour
Shivering in Piglets
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Placed in either thermoneutral (TN) or cold (C) environment
between 6 and 54 hours of life
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C pigs had slightly lower rectal temps (-1.1°C)
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Sustained shivering was also associated with:
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Decrease in muscle glycogen (-47%)
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Decrease in total lipid content (-23%)
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Increase in muscle cytochrome oxidase activity (+20%)
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Suggests that cold exposure increases muscle oxidative
potential
+ Energy Metabolism During Perinatal Period
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Prenatal and Neonatal Glycogen Levels
in the Pig
+ Consideration of the Chinese Meishan Pig
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Meishan pigs farrow 3-5 more
piglets and have a decreased prewean mortality when compared to
common western breeds
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Meishan pigs have shown to have
greater glycogen levels in fetal
livers
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As neonatal pigs cannot use nonshivering thermogenesis, glycogen
stores play a key role
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There is a noted correlation between
gylcogenolysis and increased
survivability
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Conclusions from this Data
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Maternal insulin (MS > WC, Irrespective of day)
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Fetal liver glycogen (MS > WC at day 110)
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Fetal insulin & glucagon (MS > WC at day 110)
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Fetal glucose (MS>WC at day 110)
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Meishan piglets exhibit increased production of liver
glycogen at late gestation that is driven by increased
availability of glucose and insulin within the fetus
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Non-Shivering Thermoregulation:
BAT vs WAT
Brown Adipose Tissue
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Main method of regulating
core body temperature in most
infant mammalian species
White Adipose Tissue
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Present in adults
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Acts as a storage facility for
ATP production
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Present in neonates
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White in color
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Expels heat in times of cold
stress
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Some mitochondria
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Brown in color due to high
amount of UCP-1
(Thermogenin)
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High amounts of
mitochondria
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BAT
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Essential for non-shivering thermogenesis
 Composes 1-5% of BWT in human
neonates (Brondani et al. 2012)
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Major source of BAT in neonatal humans
and most mammals is located around the
central organs like the heart, kidneys
(Clark, 1997)
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Newborn must activate and utilize these
BAT storages shortly after birth
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UCP-1 Mechanism
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Increase in norepinephrine production as a result of cold
exposure
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Increased norepinephrine results in the increased
production of thyroxine (T4), which is then converted to
triiodothyronine (T3)
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T3 upregulates UCP-1 activity
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Protons can now enter the mitochondria and are “uncoupled”
to ATP synthesis
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This allows the mitochondria in BAT to produce heat without
storing energy as ATP (knobel et al.)
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UCP-1 Mechanism:
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https://www.youtube.com/watch?v=BHZhUbeI8FQ
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What does UCP-1 and this
supplement have in common?
2,4-dinitrophenol
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2,4-dinitrophenol
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First used in French munitions factories during WWI
 Workers felt fatigue, sweat excessively, lost weight, and experienced
elevated body temperatures
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This led two Stanford scientists to research the compound in
1933
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Reported a 50% metabolic increase in subjects
Used as a dieting aid
 Acute toxicity
 Increased metabolic rate
 Nausea, vomiting, dizziness
 Chronic = cataracts, skin lesions
 Cause effects on the bone marrow, CNS and CVS
 Death has also occurred
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Brown Adipose Tissue (BAT)
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In full term infants brown fat is 4 % -10% of adipose deposits.
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In preterm infants, brown fat may not be found until 26-30
weeks gestation, and then only in small amounts.
Symonds, 2012
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Cannon et al. 2004
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Intrauterine growth restriction
(IUGR)
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IUGR is due to the pack of or impairment
in the delivery of nutrients to the fetus
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Satterfield et. al. 2013 focused on feeding
ewes different amounts of of feed (50% and
100% of total feed) starting on day 35 of
gestation
Intravenous injections of either saline
(control) or L-arginine 3x daily from day
100-125 gestation
 Fetal weight was restricted and decreased
in the feed restricted ewes compared to
the 100% feed group
 However, underfed ewes that received the
L-arginine injection had an increase in
peri-renal BAT mass by 48% when
compared to the saline ewes
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Neonatal Hypothermia
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Hypothermia can be directly associated with an increased
pre-wean morbidity and mortality
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Vasoconstriction
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Central and peripheral cyanosis
Increased respiratory rate
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70-80% of preweaning mortality occurs within the first 3 days
after farrowing (Tuchscherer et al. 2000)
relatively small and underdeveloped muscles
As a result of hypoxia and decreased surfactant production
Lethargy
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Hypothermia Prevention Methods:
Humans:
• Plastic bubble wrap
• Stocking hats
• blankets
Animals:
• Heat lamps
• Blankets
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Mechanisms of Heat Loss
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Conduction
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Convection
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Direct heat loss from skin to an object
Loss of heat via air flow
Evaporation
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Loss of heat from water evaporating from skin
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Beige (Brite) Adipose Tissue
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Inducible “brown-like” adipocytes that develop in white fat
as a response to certain activators
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Unlike BAT, which expresses high levels of UCP-1 even at
basal metabolism, Brite AT expresses these genes only in
response to certain activators (Harms et al. 2012)
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i.e., Cold or β-Agonist
Himms-Hagen et al. found that most beige adipocytes arise
from pre-existing cells that were presumed to be mature
adipocytes
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Origin of Beige Adipose Tissue
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Wang et al. labeled mature adipocytes in WAT using LacZ
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Mice were then exposed to cold or treated with β-adrenergic
agonists to elicit formation of beige adipocytes
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Results: A majority of newly-recruited UCP-1 adipocytes
were not marked by LacZ Rather than arising from mature
adipocytes, most, if not all, beige adipocytes arise from a
precursor population
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MORE RESEARCH!!!
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There is little knowledge known about what signals/genes
trigger the differentiation between BAT and WAT precursor
cells and (Satterfield, 2013) was the first research done on LArginine and its affects on fetal BAT development. Further
exploration in this field would be beneficial for increasing
survival mechanisms in our preterm human and livestock
species.
Questions?
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References
Asakura H. 2004. Fetal and neonatal thermoregulation. J Nippon
Med Sch 360-370.
Clarke L., Buss D.S., Juniper D.S., Lomax M.A., Symonds M.E. 1997.
Adipose tissue development during early postnatal life in ewereared lambs. Exp Phys 82:1015-1027
Cannon B., Nedergaard J. 2004. Brown adipose tissue: function and
physiological significance. Physiol Rev 84:277-359.
Symonds M., Pope M., Sharkey D., Budge H. 2012. Adipose tissue
and fetal programming. Diabetologia 55:1597-1606.
Satterfield M., Dunlap K., Keisler D., Bazer F., Wu G. 2013. Arginine
nutrition and fetal brown adipose tissue development in nutrient
restricted sheep. Amino Acids 45:489-499.