ENERGY, FOOD,

HEAT AND
TEMPERATURE
BALANCE

1 Five Lectures by Andrew Murray

Part 1A Physiology of Organisms

Lecture 3

ajm267@cam.ac.uk
 BODY HEAT AND
TEMPERATURE
2
ENERGY BALANCE

Food Intake = Energy used + Weight gain

(Work done)

Food intake = Heat production + Weight gain

3
We inevitably make heat as a by-product of our
everyday biochemistry and exercise.

We have to be careful not to overheat.

However, ……..

We often have to use energy resources just to make

4
heat, otherwise we will get too cold
 Many physical processes increase in speed in
direct proportion to absolute temperature

RT  outside
E log e  
zF  inside 
The Nernst Equation:-
note that T is degrees absolute, degrees Kelvin

5
 Physical processes increase in speed only
slowly with temperature (at room/body temp)
Speed of reaction

Physical process
Q10 = 1.03

Absolute zero
20-30 deg Celsius
6
Enzymatically-catalysed processes increase in speed in much
faster with temperature

Enzymatic process
Q10 = 2 - 3
Speed of reaction

Physical process
Q10 = 1.03

Absolute zero
20-30 deg Celsius
7
So:

The higher our temperature, the quicker will be our

“chemistry”

But
At high temperatures, proteins denature!!

We compromise and fix body temperature at

about 37C
8
Hot vents

Life at 100°C plus !!!

9
Some contrasts:

warm-blooded vs cold-blooded

Birds, mammals Fish, reptiles, slugs, etc

10
Some contrasts:

warm-blooded vs cold-blooded

homeotherms vs poikilotherms

Birds, mammals Fish, reptiles, slugs, etc

11
 Some contrasts:-
Poikilotherm
Body temperature “cold-blooded”

Homeotherm
“warm-blooded”
generate extra heat promote heat loss
endotherm

Environmental temperature
12
Some contrasts:

warm-blooded vs cold-blooded

homeotherms vs poikilotherms

does that mean ???

mammals/birds vs everything else

sort of, apart from all the exceptions

13
A homeothermic mammal?????

day

night

14

See Appendix E
 A poikilothermic fish?????

e rm
th
il o
tuna po
i k

Its muscular work keeps it

warmer than the sea. 15
It is an endotherm.
Beware: adders in Spring!!

Reptiles can control their body temperature by

moving in and out of the sun.

They use the sun’s heat -- ectotherms

16
Beware: adders in Spring!!

It’s warm enough to wake them up.

But, it’s not hot enough to get them working fast:

They cannot get out of your way quickly enough;

you startle them -- they bite. 17
Some contrasts:

warm-blooded vs cold-blooded

homeotherms vs poikilotherms

endotherms vs ectotherms

does that mean ???

mammals/birds vs everything else,

including plants??

sort of, apart from all the exceptions

18
Endotherms vs ectotherms

Good thing:
Endotherms can still operate when the weather gets cold

Bad thing:
But, endotherms must eat extra food to keep their bodies
warm; in cold weather, it might not be easy to find that
food.

Small endotherms spend all their time trying to find food;

ectotherms can just go into torpor when food is a problem.

19
Do people keep their temperature
absolutely constant??

Are we utterly homeothermic?

20
 Rectum  “core”

That’s whatTemperature
you’d expectoffrom a homeotherm
skin in different
body parts

21
environmental
 Rectum  “core”

Temperature of
skin in different
body parts
Tympanic temperature
(ear drum)
is a measure of brain
temperature

22
environmental
 Rectum  “core”

Temperature of
skin in different
body parts

23
environmental
 Cold Warm
environment environment

Keep heat in
brain and
essential organs

24
DO SOME PEOPLE “FEEL THE COLD”
MORE THAN OTHERS?

25

http://www.timesonline.co.uk/tol/life_and_style/health/article5106854.ece
 Fahrenheit!!!!!

menses

26
 Liver glycogen
running out

Noon midnight Noon

27
 RETENTION OF
BODY HEAT
28
 Cold Warm
environment environment

Thermogram of a face
shows nose and ears
are colder than the rest

green = “cold”

29
In the “Himalayan” rabbit &
the Siamese cat,

Melanin is only made properly

in cold tissue.

The “pointy” bits are cold:-

The “pointy” bits are black

30
 Heat loss from long-thin thing

Warm core Cold outside

Heat Heat lost to cold outside

A leg!

31
 Counter-current exchange

Warm core Cold outside

heat

A leg!!

32
 Counter-current exchange

Warm core Cold outside

Heat is retained, short-circuited

and sent back to the core

33
 Counter-current
exchange
to retain heat

34
Heat from arteries
transferred to veins
Counter-current The nasal passages retain both
heat and expired moisture
exchange
to retain heat

Heat from warm exhaled air 35

transferred to cold veins
 Counter-current The nasal passages retain both
heat and expired moisture
exchange
to retain heat

36
Also a means of reducing
water loss – exhaled air would be both warm and moist
 Counter-current
cold
hot
exchange
to retain heat

dolphin
37
Heat from arteries
transferred to veins
 But,

Dolphin’s Testes
are internal

dolphin
38
 But,

Testes don’t like

to be warm!!!

A bull
39
Counter-current attempts to retain heat in body

Coolish blood
from fluke

warm blood
from heart

Gives coolish
blood to testes

40
Cold (!!) from veins Counter-current
transferred to arteries cools blood to testis
 Bit of a problem with the logic:
Testis!!

Elephants have
internal testes
but no cooling system

41
That was:
Counter-current exchange
from warm arteries to cold veins!!!

And now:
Counter-current exchange
from warm veins to cold arteries!!!
42
 Tuna

erm
h
ilot
oik
p

43
Heat from warm veins
transferred to cold arteries A cold-blooded poikilotherm????
 44

Top speed (through water!) of 90 kph!!

 heat
from metabolism

+ The equation for

temperature regulation
37C
core
temperature
_
We want to keep “core temperature”
constant or balanced
+

heat loss
to environment 45
 heat food
from metabolism

+ The equation for

temperature regulation
37C
core
temperature
_
We want to keep “core temperature”
constant or balanced
+

heat loss
to environment 46
 heat food
from metabolism

+ The equation for

temperature regulation
37C
core
temperature
_
We want to keep “core temperature”
constant or balanced
+

heat loss
to environment 47
 heat BMR

from metabolism 80 W

+
37C
core
temperature

+
_
heat loss Just balances heat loss to
to environment 30°C environment 48
 heat
from metabolism
To stay warm in a cooler
+ environment needs 2
strategies
37C
core
temperature 1. Generate more heat
_ 2. Minimise heat loss
+
X
heat loss
to environment 49
 HEAT
PRODUCTION
50
Today:

Mechanisms for deliberately

increasing heat production

51
GENERATING MORE HEAT

 Muscular work is particularly effective:

 Wegenerate 10x as much heat as at rest

during extreme exercise. (1 kW vs. 100 W)

 We could warm up 1°C in just 5 minutes

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GENERATING MORE HEAT
 Extra muscular work is very effective - shivering

53
Heat production:
Reticular formation, in
the brain stem

Shivering is controlled
by the hypothalamus
muscles

hypothalamus 54
GENERATING MORE HEAT
 Extra muscular work is very effective – shivering
increases heat production 3-5 fold
 But you can’t shiver all winter...

 So you need extra metabolic energy production

55
Acclimatisation in a person:
On moving to cold environment, the person’s heat
production increases immediately. Over 10 days,
the amount of shivering decreases. Some other
means of producing heat must have been recruited.

Heat production Amount of shivering

56
 Heat production:
Basal metabolic rate

The BMR is affected

by the hypothalamus

via the anterior pituitary

and the thyroid gland

hypothalamus 57
 hypothalamus
supra-optic
nucleus neurosecretory median
cells eminence

mammillary
body
optic chiasm

Anterior
pituitary posterior
front pituitary
anterior
pituitary

"tropes"

blood flow

The anterior pituitary secretes 6-7 protein hormones

from 6-7 specialised cell types (“tropes”) 58
 hypothalamus
supra-optic
neurosecretory median
environmental cold
nucleus
cells eminence

_
Brain
mammillary
body
optic chiasm
TRH
+ _ somatostatin
Anterior
pituitary posterior _
front
anterior pituitary thyrotropes
pituitary

"tropes"
TSH
blood flow
thyroid
TSH TSH gland

thyroxine T3

Thyroid increased BMR

in neck
59
Thyroxine/T3
 environmental cold
The thyroid secretes two hormones:-
_
Brain
Thyroxine (T4) has 4 iodine atoms
TRH _ somatostatin
Tri-iodothyronine (T3) has 3 iodine atoms
+
_ T3 is much more potent than T4
thyrotropes

TSH T3 is synthesised from T4

thyroid
gland

The strength of thyroid action depends on how

thyroxine T3 much T4 is converted to T3
and the rate of this conversion can be
changed to meet different heat needs
increased BMR

60
 environmental cold

_ In cold weather,
Brain

TRH
+ _ somatostatin

_
thyrotropes
In some animals, increased TSH release
TSH from pituitary causes increased
thyroid
thyroxine/T3 secretion.
gland

In some animals including people,

there is increased conversion of
thyroxine T3
thyroxine to T3

increased BMR

61
 from Berne & Levy

62

and UnCoupling Protein (thermogenin)

 40 - 60% of the Basal Metabolic
Rate
may be spent
in pumping ions across cell membranes.

Write this in your notes

63

and UnCoupling Protein (thermogenin)

FUTILE CYCLES

heat ATP

Enzyme #2

Substrate-1 Substrate-2

Enzyme #1

ATP
heat
64
REGULAR (WHITE) ADIPOSE TISSUE IS...
 An efficient energy reserve (lecture 1)
 Quite good thermal insulation (lecture 4)

 Mechanical padding and protection (e.g. kidneys)

 Crucial to sex phenotype

 An endocrine gland (lecture 4)

 A source of “drinking” water for sea mammals

(Appendix D)

 BUT – a special kind, BROWN adipose tissue

is a source of raw heat! 65
 Brown fat – has lots of
mitochondria.

Lots of Copper-containing
cytochromes makes it brown

noradrenaline

TG = triglyceride = “fat”

oxygen

66
 CELL MEMBRANE
Proton Gradient

ENERGY TRANSFER CYTOSOL

H+ H+ H+ H+ H+
HEAT
RESPIRATORY CHAIN ATP UCP
synthase

Pi

ADP ADP
ATP ATP
WORK
Fuel O2 H2O
(& CO2 at an
O2 O2 earlier stage)

MITOCHONDRION

INNER MEMBRANE

 Fuel oxidation, and ADP phosphorylation are separate processes,

connected by the proton gradient, which can become uncoupled67–
leading to heat production
 no ATP

The H+ gradient is “short-circuited”

by thermogenin (UCP) 68

(Uncoupling Protein)
69
70
Heat production:

Brown fat is controlled

by the hypothalamus

via the
sympathetic nervous system
hypothalamus 71
Heat production:

Pituitary
thyroid
BMR
Skeletal muscle
Sympathetic NS
shivering
Brown fat 72
Acclimatisation in a person:
On moving to cold environment, the person’s heat
production increases immediately. Over 10 days,
the amount of shivering decreases. Some other
means of producing heat must have been recruited.

But, we’re not sure what “other means” is!!

Even though adult people may not have obvious

lumps of brown fat, they may have

UCP in the mitochondria of scattered fat cells and

of skeletal muscle.

73
Acclimatisation in a person:
On moving to cold environment, the person’s heat
production increases immediately. Over 10 days,
the amount of shivering decreases. Some other
means of producing heat must have been recruited.

But, we’re not sure what “other means” is!!

Even though adult people may not have obvious

lumps of brown fat, they do have UCP in the
mitochondria of scattered fat cells and
of skeletal muscle.

74
HOLD THE PRESS!!!!

75
Acclimatisation in a person:
On moving to cold environment, the person’s heat
production increases immediately. Over 10 days,
the amount of shivering decreases. Some other
means of producing heat must have been recruited.

But, we’re not sure what “other means” is!!

OK, well apparently adult people DO have obvious

lumps of brown fat, but they also have UCP in the
mitochondria of scattered fat cells and
of skeletal muscle.

76
UCP (Uncoupling Protein) in plants

When potatoes and winter wheat

are exposed to cold...

they generate more heat by expressing

UCP in their mitochondria (and maybe
other mechanisms)

77
 UCP (Uncoupling Protein) in plants

The “skunk cabbage” makes so much heat that it melts the 78

snow.
 UCP (Uncoupling Protein) in plants

The “sacred lotus” looks like an endothermic homeotherm! 79

UCP (Uncoupling Protein) in plants

80
FRENCH MUNITIONS FACTORIES – WWI

81
2,4-DINITROPHENOL

82
 CELL MEMBRANE
Proton Gradient

ENERGY TRANSFER CYTOSOL

H+ H+ H+ H+ H+
HEAT
RESPIRATORY CHAIN ATP
synthase

Pi

ADP ADP
ATP ATP
WORK
Fuel O2 H2O
(& CO2 at an
O2 O2 earlier stage)

MITOCHONDRION

INNER MEMBRANE

 Dinitrophenol is a potent uncoupler of oxidative 83

phosphorylation
2,4-DINITROPHENOL

 Increases metabolic rate – burns off fat

84
2,4-DNP – ANTI-OBESITY THERAPY?
 A few side effects…
 Extremely high body temperature
 Profuse sweating
 Intense thirst
 Loss of appetite
 Nausea and vomiting
 Diarrhoea Surprised?! You are
 Night sweats stopping your
 Headaches mitochondria from
 Muscle weakness making ATP!
 Rashes
85
 Hastened rigor mortis upon death
 CURRENT RESEARCH...
 Bruce Spiegelman’s lab, in Boston, have looked at the genes
that, when turned on, make brown fat what it is and found a key
candidate – PRDM16

PRDM16 ?

 Sadly not, however it can affect WAT cells at an earlier stage of

development (pre-adipocyte)
 A change in 1-2% of fat cells, from white to brown adipose
tissue could make all the difference. 86

http://www.the-scientist.com/article/display/54033/
 A MUSCLE-LIKE FAT?
 More recently Spiegelman has proposed that brown fat is
actually more similar to a skeletal muscle (especially Type 1
muscle) without muscle fibres, than it is to white adipose tissue.


≈
It is a mitochondria-rich, fat-oxidising organ – but produces
heat directly, rather than using ATP to do useful work through
muscle contractions. 87
 WAS POPEYE RIGHT AGAIN?
 Spinach (and beetroot)
contains a lot of nitrate

 Dietary inorganic nitrate

“browns” adipose tissue
in rats! Does this work in
humans… watch this
space!

Lee Roberts et al. Inorganic Nitrate Promotes the Browning of White Adipose 88

Tissue through the Nitrate-Nitrite-Nitric Oxide Pathway Diabetes, 2015

 NEXT LECTURE....

How to keep your cool in the Cambridge winter...

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