ANS 536 : PERINATOLOGY

Thermoregulation

Early Life is Difficult for the Piglet

“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.”

Introduction statement in “Behavioural perspectives on piglet survival” by D. Fraser 1990.

Introduction

Thermoregulation: Process by which the body is able to maintain its core internal temperature

Remaining within the thermo-neutral (TN) zone is paramount Increased rate of FA degradation, glycolysis, or

glycogenolysisHypothermia can be directly associated with

an increased pre-wean morbidity and mortality. ~70-80% of preweaning mortality occurs within the

first 3 days after farrowing (Tuchscherer et al. 2000)

Shivering Thermogenesis

Physiological response to hypothermiaSkeletal muscles begin to contract

Creating warmth via energy expenditureDependent upon glycogen stores and

cardiovascular fitness

Thermoregulation

Premature or relatively small neonates have an exceptionally large skin surface area compared to body mass

This results in proportionately more heat loss through skin than adults (Knobel et al. 2010)

Decrease in temp below resting metabolic rate results in increased metabolism for maintenance of homeostasis

US MARC Litter Statistics (Swine)

A Difficult Dichotomy

A sow is most comfortable at ~70°FIdeal environment for a piglet is 90-95°F

Lower critical temperature is ~84°F

Thermogenesis

Metabolic Processes Heat generated by oxidative metabolism of glucose

and fatsVoluntary Muscle Activity

Very limited use to newbornPeripheral Vasoconstriction

Reduce blood flow to skin Decrease heat loss from body

Nonshivering Thermogenesis Incorporation of brown adipose tissue (BAT)

Thermogenesis

Humans and ruminants are known to primarily use non-shivering thermogenesis via the use of brown adipose tissue.

Conversely, pigs completely lack brown adipose tissue and therefore rely almost exclusively on shivering mechanisms to regulate temperature (Berthon et al. 19994)

Brown Fat

In full term infants brown fat is 4 % -10% of adipose deposits.

In preterm infants, brown fat may not be found until 26-30 weeks gestation, and then only in small amounts.

Brown Adipose Tissue (BAT)

Essential for non-shivering thermogenesis Composes 1-5% of BWT in human neonates (Brondani et al.

2012)

What gives BAT its brown coloring?Contains high amount of UCP-1 or

ThermogeninUCP-1 allows the mitochondria to generate heat rather

than ATP

Signs/Symptoms of Neonatal Hypothermia

Vasoconstriction Central and peripheral cyanosis

Increased respiratory rate As a result of hypoxia and decreased surfactant

production

Lethargy

Mechanisms of Heat Loss

Conduction Direct heat loss from skin to an object

Convection Loss of heat via air flow

Evaporation Loss of heat from water evaporating from skin

UCP-1 Mechanism

Increase in norepinephrine production as a result of cold exposure

Increased norepinephrine results in the increased production of thyroxine (T4), which is then converted to triiodothyronine (T3)

T3 upregulates UCP-1 activityProtons can now enter the mitochondria and

are “uncoupled” to ATP synthesisThis allows the mitochondria in BAT to

produce heat without storing energy as ATP (knobel et al.)

Because, seriously, is ATPeven that important?!

What do UCP-1 and this supplement have in common?

2,4-Dinitrophenol

First used in French munitions factories during WWIWorkers felt fatigue, sweat excessively, lost weight, and

experienced elevated body temperatures

This led two Stanford scientists to research the compound in 1933 Reported a 50% metabolic increase in subjects

UCP-1 Mechanism

https://www.youtube.com/watch?v=BHZhUbeI8FQ

UCP-1

Brondani et al. 2012

Cannon et al. 2004

Cannon et al. 2004

Beige (Brite) Adipose Tissue

Inducible “brown-like” adipocytes that develop in white fat as a response to certain activators

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) 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

Origin of Beige Adipose Tissue

Wang et al. labeled mature adipocytes in WAT using LacZ

Mice were then exposed to cold or treated with β-adrenergic agonists to elicit formation of beige adipocytes

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

Thermoregulation in Piglets

Due to the lack of BAT in piglets, rate of thermogenesis is dictated by the amount of stored glycogen

Ingestion of colostrum Increased metabolic rate

There is a direct correlation between heat production and colostrum intake

Colostrum intake & Thermoregulation

Dividich et al. observed colostrum intake in two different groups of pigs. 18-20°C (CG=Cold Group) & 30-32°C (WG=Warm

Group)CG pigs consumed 38.1% less colostrum (P<0.01)Positive correlation between birth weight in colostrum

intakeColostrum intake could be effectively measured from

birth weight (R2=.75)5 of 39 (12.8%) from CG group died within 3 days

post-partum0 of 41 from WG died within 3 days post-partum

Metabolic Affects of sustained 48-Hr shivering in piglets

Placed in either thermoneutral (TN) or cold (C) environment between 6 and 54 hours of life

C pigs had slightly lower rectal temps (-1.1°C)

Sustained shivering was also associated with: Decrease in muscle glycogen (-47%) Decrease in total lipid content (-23%) Increase in muscle cytochrome oxidase activity

(+20%) Suggests that cold exposure increases muscle oxidative

potential

Energy Metabolism During Perinatal Period

Mellor & Cockburn 1986

Prenatal and Neonatal Glycogen Levels in the Pig

Consideration of the Chinese Meishan Pig

Meishan pigs farrow 3-5 more piglets and have a decreased pre-wean mortality when compared to common western breeds

Meishan pigs have shown to have greater glycogen levels in fetal livers

As neonatal pigs cannot use non-shivering thermogenesis, glycogen stores play a key role There is a noted correlation between gylcogenolysis

and increased survivability

Miles 2014

Miles 2014

Serum Nutrients

Miles 2014

Serum Regulatory Components

Miles 2014

Conclusions From This Data

Maternal insulin (MS > WC, Irrespective of day)

Fetal liver glycogen (MS > WC at day 110)Fetal insulin & glucagon (MS > WC at day

110)Fetal glucose (MS>WC at day 110)

Meishan piglets exhibit increased production of liver glycogen at late gestation that is driven by increased availability of glucose and insulin within the fetus

Kangaroo Mother Care

Low birthweight babies are nursed nakedData implies that KMC may result in:

Lower infection rates Reduce apneic episodes Similar or enhanced blood oxygenation

Bergman et al. 2004

Other Prevention Methods

Plastic wrapStocking hats

Questions?Questions?