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Conclusion?

Tryptophan Serotonin

Tryptophan derivatives: melatonin (sleep) + auxin (growth)

Vertebrates: serotonin methylated into melatonin in pineal gland

Vertebrates: serotonin levels higher on bright days

Seasonal Affective Disorder [SAD]

Tryptophan-containing proteins:

chlorophyll, rhodopsin receptor, 5-HT1A receptor

Evolutionary Aspect:

From early eukaryotic cells to humans.

Serotonin

  • Highly conserved
  • Aves and Mammalia

[peripheral secretion]

"Did circulating serotonin emerge with endothermy?"

  • Vasoactive substance
  • Widens under higher temperatures
  • Narrows under lower temperatures + platelet morphology change

  • Ectotherms do not have circulating serotonin
  • Exceptions:

Leatherback sea turtle, Green sea turtle, American alligator

Partial endothermy?

Migration Background

Avoid inbreeding

  • Chimpanzees + gorillas: females leave
  • Old World monkeys: males leave
  • Humans: we go to college

Why risk it?

Who had the lowest lymphocyte count?

Who had the highest levels of Cortisol?

Ice Age

Agricultural Revolution

Industrial Revolution

Examined similarities between human and dolphin metabolism

  • Large brains = high metabolic needs
  • Carnivore connection = human shift to high protein diet parallels shift from high carbohydrate diet (on land) to high protein diet (of fish in sea)

Dolphins transition in/out of Diabetes I/II without ketoacidosis

Some mammals fast for months in a diabetes-like state without ketoacidosis

From Squalene to Steroid...

Squalene Sources

Biosynthesis!

The Transformation from Isoprene to Steroid

Major Classes of Steroids in the Endocrine System:

ISOPRENE

Sex Hormones

Adrenal Cortex Steroids

5 Carbons

http://www.fao.org/3/a-y5945e/y5945e02.pdf

  • Estrogens
  • Progesterone
  • Androgens
  • Cortisone
  • Cortisol
  • Aldesterone

Terpenes: isporene units

joined together

BACKGROUND on a

Molecular Level

Where does squalene come from?

Sharks

  • Abundantly found in shark liver oil
  • Superorder Squalomorphi (squalomorph sharks)

Plants All plants make squalene

Humans All animals make squalene;

but how...?

MONOTERPENE

10 Carbons

"From Terpenes to Steroids Part 2: Squalene, Cholesterol, and Steroids." Khan Academy

2 Isoprene units

Example: menthol

Triterpene

Cyclization reactions occur in the liver to transform the squalene into cholesterol.

SESQUITERPENE

30 Carbons

6 Isoprenes

or 3 Monoterpenes

15Carbons

3 Isoprene Units

Example: Ginger

"From Terpenes to Steroids Part 2: Squalene, Cholesterol, and Steroids." Khan Academy

Testosterone and Aggression

Serotonin: Biosynthesis

Serotonin Functions

Which came first? Chicken (Testosterone) or the Egg (Aggression)?

The "Permissive Effect"

Key:

1 Triangle = 20%

Gray = Absent

Blue = Present

Azmitia 17

After Castration + Injection = Aggression Level

EVOLUTIONARY CONNECTIONS through a neurotransmitter

Tryptophan hydroxylase + O2

0% Testosterone Post-Castration 100% Pre-Castration Testosterone 100% Pre-Castration Aggression

Azmitia 9

Tetrahydro-biopterin +

aromatic amino acid decarboxylase

Azmitia 9, 17

0% Testosterone Post-Castration 20% Pre-Castration Testosterone 100% Pre-Castration Aggression

Food Intake

Thermoregulation?

Azmitia 9

0% Testosterone Post-Castration 200% Pre-Castration Testosterone 100% Pre-Castration Aggression

Sleep

Mood

20 - 200% increase in (injected) testosterone -- return to same level of aggression.

400% increase in (injected) testosterone -- impact on aggression; seen in steroid use.

Azmitia 16

Azmitia 17

Muller and Jacobs 17

Sapolsky, The Trouble with Testosterone: "Will Boys Just Be Boys?"

Maurer-Spurej, "Circulating Serotonin in Vertebrates."

Azmitia, Handbook of the Behavioral Neurobiology of Serotonin

Transfer & Stress

Insulin Resistance: Type II Diabetes

Insulin: Pathophsyiology of Type I Diabetes

Different Personality Types & Stress

Diet: Introducing Carbohydrates

DepressION

  • Agricultural development
  • Foods had low glycaemic index
  • Slight increase in blood insulin

In the beginning...

Those who battle depression are up against a daily battle; it's difficult to work up the motivation, desire, or energy to try to "fix" things. This mentality seeps into their stress response: they do not cope with real or perceived stressors. This causes elevated stress hormone levels in their blood.

Carnivore Connection:

Hobbes,

the new

Alpha

Repressed

TYPE A

Sapolsky 37

3x Hobbes

6x Hobbes

< 1/4 Average

5% of the population

Troop Average

Ruto

Fatso

Hobbes

Unmolested

female

Molested female

Diet: High protein, high carbohydrate

Diet: High protein, low carbohydrate

Competitive, overachieving, impatient, perfectionist, hostile when things go wrong...

Hardworking, productive, disciplined, "Cross T's and dot I's," everything structured, complete control of emotions, "perfect"

Milling of cereals

  • Changed rate of carbohydrate digestion/absorption
  • Starch easily digested
  • Postprandial glycaemic and insulin response

--> 2-3 x higher than coarsely-ground flour/whole grain

Potatoes introduced to West

  • High glycaemic and insulin responses

Modern High Glycaemic Index

Insulin resistance --> Hyperinsulinaemia --> Linked to Type 2 Diabetes Pathogenesis

3x Molested Female

CASE STUDY:

Evolution

of

Diabetes

Body's Response: Insulin Resistance

  • Metabolic adaption with periodic starvation

  • Insulin sensitivity: disadvantage especially during pregnancy

Stress

Are you Type A?

1/3 Female not attacked

http://www.huffingtonpost.com/2014/01/13/are-you-a-type-a-or-type-_n_4549312.html

Pancreas

Functions:

1) Exocrine--secretes enzymes for digestion

2) Endocrine--hormones and metabolism

Cells:

Beta --secrete--> Insulin into blood

Alpha--secrete--> Glucagon

Auto-immune Disease

Diabetes: Beta cells are destroyed

  • Chain reaction subsequently occurs...

AnxiETY

Unmolested Female

Colagiuri, "The 'Carnivore Connection' -- Evolutionary Aspects of Insulin Resistance."

Molested

Female

Pancreas

Endocrine Functions

Beta & Alpha Cells

Auto-immune Disease

Hyperglycemia

Stress-Response

Chronically Elevated Stress Response: Why?

Appearance keepers: care too much about appearing perfect, they actively repress the imperfections

Self deceivers: psychology tests reveal some are more subconsciously anxious than they even realize; don't consciously recognize their experiences as being 'anxious' or 'stressful'

Others: exhibit an overactive adrenal gland, and as elevated glucocorticoid levels as those with anxiety. But, an EEG (of their brain) showed a hyperactive frontal cortex. They're always using their frontal cortex, which is energetically expensive!

Struggling with anxiety may mean constantly feeling on edge without knowing why, feeling intimidated to socialize, or always expecting the worst.

Individuals with anxiety disorders are persistently mobilizing a stress response in preparation. Their "homeostasis" baseline for stress hormones in the blood (epinephrine, norepinephrine, and glucocorticoids) is higher than average.

Energetics: they could eventually exhaust their system.

Dolphin Connection

High risk for cardiovascular disease

  • Easily and quickly releases (too much) stress hormone into blood
  • Tend to have hypertension and cardiovascular issues

Fatso

Sapolsky 37

The

Troop

Ruto

Sapolsky 37- 38

Type B

John Henryism

Tolerant, adaptive, flexible

Are you Type B?

Highest

Lowest

http://www.huffingtonpost.com/2015/06/16/type-b-images_n_7562420.html

Individuals "strongly agree" with a statement like "When things don't go the way I want them, it just makes me work even harder." They believe that they can "regulate all outcomes" with hard work and determination." These personality types develop hypertension, because they continuously secrete stress hormones to get the job done--no matter the obstacle.

Most common among working class African Americans.

--- Hobbes

--- Molested Females

--- Unmolested Females

--- Subordinate Males

Sapolsky 37

"Pathophysiology - Type I Diabetes." Khan Academy.

Sapolsky, "The Burden of Being Burden-Free"

Venn-Watson, "Dolphins and Diabetes: Applying One Health for Breakthrough Discoveries."

Sapolsky, "The Young and the Reckless"

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