Ch. 9 Internal Regulation

Health Consequences of Obesity

1. Hypertension

2. Sleep Apnea

3. Arthritis

4. Peripheral Artery Disease

5. High Cholesterol & Triglycerides

6. Coronary Heart Disease (also caused by diabeties)

7. Diabeties

8. Diabetic Complications

9. Social Disability

Obesity is ranked as…

One of the top 5 health problems in developed nations according to the World Health Organization

Body Mass Index (BMI)

• Is used as a measure of body fat

  • BMI = body weight/ (height²)

Obese

• BMI >/= 30 kg/m²

  • More than 1 in 3 adults, aged >/= 20yrs (>60 million)

Claude Bernard (1813-1878)

• French psychologist who is considered the “father” of modern experimental psychology

• Studied the physiology of digestion, particularly the role of the pancreas

• Contributed to the understanding of glucose regulation in the liver

Claude Bernards Finding on Weight Regulation

• Weight is regulated homeostatically

  • Proposed the concepts of:

    • Homeostasis = controlled stability of the ‘internal milieu’ (i.e., internal environment) of cells & tissues

    • Feedback control loops = explained how certain systems work as homeostatic mechanisms

Homeostasis

• Of biological processes Kees certain target body variables at a specific SET POINT or within a fixed range

  • Ex: body levels of water, oxygen, pH, glucose, sodium chloride, protein, fat.

Homeostasis

• Bio-mechanisms that reduce discrepancies from the set point are known as NEGATIVE FEEDBACK PROCESSES

• For many years it was hypothesized that obesity was a consequence of a failure of body weight homeostasis

Hunger

• Is the stimulus that drives our need to ear

  • When our bodies need fuel, signals are sent from the empty stomach & intestine that trigger feelings of hunger

Signals of Hunger

• processed by the brain but we can override them:

  • delay hunger response actions e.g., people who fast or starve typically have lower hunger

  • Ear more than we need by ignoring satiety receptions that signal fullness e.g., “supersize me”

Process of digesting food

Digestive System

• Function of the digestive system is to break down food into smaller molecules that the cells can use

Digestion

• Begins in the mouth where enzymes in the saliva break down carbohydrates

Stomach

Hydronic acid & enzymes in the stomach digest proteins

Small Intestine

• Has enzymes that digest proteins, fats, & carbohydrates & absorbs digested food into the blood stream

Large intestine

• Absorbs water & minerals & lubricates the remaining materials to be excreted

Satiety

• Is the feeling of fullness that stops appetite & hunger signals

  • The brain regulates eating through messages from the mouth, stomach, intestines, fat cells & elsewhere

• Satiety signals that originate in the stomach are delayed from the start of eating, so it is easy to overeat before satiety signals are received & acted upon

• The LENGTH OF TIME FOOD STAYS IN THE STOMACH & INTESTINE affects the duration of satiety & initiation of hunger signals

• Distention of the duodenum can also produce feelings of satiety

  • The duodenum releases cholecystokinin (CCK) & GLP-1 to restrict flow through the duodenum causing the stomach to slow gastric emptying.

  • Both CCK & GLP-1 signal the brain satiety mechanisms

Gastric bypass surgery

• is the removal or sewing off of part of the stomach

• Decreased stomach size allows distention of the stomach to produce satiety sooner

• People who have had their removed surgically (e.g., cancer) still report satiety. So stomach distention is to the only satiety signal

Oral Factors

• The desire to taste & have other mouth sensations, such as chewing, are also factors in hunger & satiety

• Persons who cannot swallow may have stomach feeding tube inserted

  • Food is then placed directly into the stomach but these persons report not feeling satisfied when fed;

    • They need to chew food to feel satisfied

• So untasted meals are unsatisfying → cold diminish taste perception & food satisfaction

Foods high in protein have…

• Foods high in protein have a high satiety value because they take more time to digest… thus, high protein diets are popular

Foods high in fiber have…

• Foods high in fiber have a high satiety value because they stay in the stomach & intestine for longer periods of time than foods that contain concentrated sugars or highly processed foods that digest & absorb readily

  • People who consume quantities of whole grain products, vegetables & fruits often feel no hunger because their satiety signals remain “on”.

Foods high in fat have…

• Foods high in fat although calorie dense, have a low satiety value. They fail to trigger the satiety signals.

  • So we often over-consume high fat foods, which tend to have the most calories

• Unfortunately, many high fat foods trigger appetite

• Researchers once thought that all fat was bad, but we now know that they were wrong

  • Fat is a major source of energy & helps the body absorb essential vitamins

• is it sugar? Glucose vs fructose; food high in fructose lead to fatty liver → insulin resistance → hunger & insulin levels increase → central obesity

Stomach Wall Stretching

• With eating is conveyed by the vagus nerve to the brain

• The splanchnic nerves convert info about STOMACH NUTRIENT CONTENT

In between meals,

• INSULIN LEVELS ARE LOW: hunger increases

• GLUCOSE LEVELS ARE LOW:

  • Glucagon released & liver cells convert to glycogen back into glucose, which returns to the blood & slows the return of hunger

In Type 2 diabetes, INSULIN RESISTANCE (IR) occurs:

• IR is the decreasedability for insulin to get glucose into body cells

• More insulin needs to be secreted to get the job done

EARLY after type 2 diabeties onset…

• To overcome the insulin resistance, after eating, the body releases high levels of insulin

• So the person typical experiences:

  • Weight gain

LATE in Type 2 diabetes,

• As the body is not able to produce enough insulin, not enough glucose is able to enter the cells

• so the person typically experiences:

  • More hunger

  • A loss of weight [wasting]

Hypothalamic Mechanisms of Eating

• Damage to the LH results in loss of appetite

• The PVH usually inhibits the LH to prevent feeding

• Feeding occurs when the Arcuate Nucleus (ARC) inhibits the PVH, thereby releasing the LH

CNS Eating Mechanisms

• The ARCUATE NUCLEUS (ARC) IN THE HYPOTHALAMUS has 2 sets of neurons that detect either HUNGER OR SATIETY SIGNALS

CNS Eating Mechanisms PT.2

• Output from the ARC goes to the PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS (PVH)

• When ARC hunger-sensitive neurons inhibit PVH, eating occurs

• When ARC satiety-sensitive neurons excite the PVH, eating stops

Satiety signals from ARC to PVH:

• EXCITATORY TRANSMITTER melancortin

Signals that trigger hunger

1. taste pathways

2. Decrease in leptin levels

3. GI release of ghrelin (Ghrelin rises before a meal to signal hunger & triggers stomach contractions.)

Signals that trigger satiety

• GI distention triggers CCK release

• Increase in leptin levels

• Increase in blood glucose & insulin levels

How does one become fat or skinny?

Leptin Hypothesis

• High leptin normally inhibits hunger

  • some obese persons have a genetic inability to produce leptin (LEPTIN SYNTHESIS DEFICIT) → more hunger

  • Some obese persons display less sensitivity to leptin (LEPTIN RESISTANCE)

    • I.e., they perceive less leptin than actually is present → more hunger

Melanocortin Hypothesis

• Melanocortin normally excites the PVH to inhibit the LH & stop eating.

  • Some obese persons have a MUTATED MELANOCORTIN RECEPTOR GENE

    • So they overeat & become obese because their PVH is not able to receive the satiety signal

Overall Neurobiological Model of Eating

Conclusion

• Body weight is the 2ND HIGHEST HERITABLE TRAIT

  • So their is a very strong genetic message demanding that our body weight will be similar to our parents

• There are EXPLICIT NEUROBIOLOGICAL MECHANISMS that account for why we regulate body weight around a set point range

• Of all the machinists that are known, WILL POWER, is NOT very likely to be one of them

• When we BETTER UNDERSTAND THE INTERACTIVE NEUROBIOLOGICAL MECHANISMS UNDERLYING EATING, it will be possible to deign interventions to help overweight & obese persons maintain a healthier body weight