Energy, Starvation and Obesity

Question 1

What is the Body Mass Index (BMI)?

Answer 1

BMI = weight in kg / (height in m)²

It is a measure of persons weight relative to their height

The BMI categories are:

• Underweight = <18.5
• Normal = 18.5 - 25
• Overweight = 25 - 30
• Obese = 30-40
• Morbidly Obese = 40+

BMI is an imperfect predictor of ideal weight:

• For age >35; BMI =27 adds little extra risk that a BMI = 20
• Mesomorphic athletes have high BMI without any inherent risk

Question 2

Contrast the different fat profiles of males and female at the onset of puberty

Answer 2

At puberty, females gain fat while males lose fat.

Females gain fat to make them suitable for child rearing -> women with low fat often lose their menstrual cycle (amenorrhea)

Question 3

How should the BMI be applied to children?

Answer 3

Although BMI = 25 is healthy in adults, this is obese for children.

When applying the BMI to children you must apply the BMI to a standardised curve due to the changing body proportions experienced in childhood.

Question 4

How can body fat be measured?

Answer 4

1. Caliper measurements of skinfold thickness
2. Body density measurements by immersion in water (hydrodensity)
3. Bioelectrical impedence (fat people are better insulators

Question 5

What waist circumference sizes are associated with increased risk of metabolic complications?

Answer 5

Sex - increased risk - substantially increased risk

Male > 94cm / >102cm

Female >80 cm / >88cm

Question 6

Explain the concept of protein sparing

Answer 6

Protein will be used structurally when enough energy is provided by carbohydrate and fat - allowing protein to be preferentially used structurally and not for gluconeogenesis

There are no storage proteins and a healthy body

The human body contains 12 kg of protein. It can
readily lose about 400g from muscle mass, but continued losses cause stress.

Question 7

What happens to the gut lining during long term starvation?

Answer 7

Long term starvation leads to progressive intestinal villi atrophy

There is nothing to absorb during starvation so the gut cannibalises itself -> providing 60g of protein to use for energy production/day

The sloughing of the intestine complicates refeeding because the gut has poor resorbtive capacity. Milk is often used for refeeding because it has equal portions in energy of protein, carbohydrate and fat.

Lactase may need to given supplementary

Question 8

Elicit the differences between Kwashikor and Marasmus conditions

Answer 8

Both conditions arise from protein-energy malnutrition states.

Kwashikor

• Moderate energy deficiency
• Severe protein deficit
• Oedema with some subcutaneous tissue
• These children have enlarged fatty
  liver, low serum albumin and oedema (fluid
  accumulation = pot belly
• Aflatoxin, derived from aspergillus fungus on corn, contributes to the severity of
  kwashiorkor by the formation of aflatoxin epoxides -> reacts with guanin in DNA -> cell death/cancer

Marasmus

• Severe energy deficit
• Severe protein deficit
• ‘skin and bones’ appearance with little or no subcutaneous tissue

Question 9

Discuss the epidemiology of lactose intolerance

Answer 9

In humans, in non-dairy consuming societies, lactase production usually drops about 90% during the first four years of life.

Populations that have adapted to drink milk as adults have a range of mutations on chromosome 2 which reduce the shutdown in lactase production.

Question 10

In reference to nitrogen balance, what factors may alter this nitrogen use

Answer 10

Positive Balance = nitrogen in > nitrogen out

• During growth more nitrogen is consumed than excreted to build proteins

Neutral Balance = nitrogen in = nitrogen out

• General basal state

Negative Balance = nitrogen in < nitrogen out

• More is excreted than consumed
• Occurs in starvation, burns victims, post-operative patients and AIDS patients

Question 11

What is cachexia?

Answer 11

Cachexia is an extreme example of loss of muscular and adipose tissue in terminal illness (often cancer).

It is caused in part by high levels of TNF-alpha that mediate a negative nitrogen balance due tot he breakdown of tissues

Question 12

What is bulimia nervosa?

Answer 12

** Bulimia nervosa** is a serious psychiatric illness
characterised by recurrent binge-eating followed by purging or overexercising

Behaviours include self-induced vomiting, fasting, overexercising and/or the misuse of laxatives, enemas or diuretics

health professionals incorrectly assume that a person must be underweight and thin if they have an eating disorder - they actually maintain a normalish body weight. A dentist is often the professional who picks up the problem -> acid of vomit rots the teeth.

Question 13

What is annorexia nervosa

Answer 13

Annorexia is an eating disorder characterized by immoderate food restriction, inappropriate eating habits and a distorted body self-perception.

There is a prevalence rate of 1-2% among schoolgirls and university students (males have one tenth of this rate). Higher rate in higher social classes.

Tend to be precipitated by:

1. Stressful life events
2. Genetics
3. Turbulent family relationships

As a result of annorexia, menses may cease, the patient may develop low blood pressure, slow heart rate, and become very sensitive to the cold.

Question 14

Discuss the positives and benefits of a vegetarian lifestyle

Answer 14

Lacto-Ovo vegetarians

Eat milk and eggs and generally do not exhibit
deficiency syndromes. Women may become Iron deficient and anaemic (recall that plants do not have blood).

Vegans

Eat no animal products. Vegans risk deficiencies in Vitamin B12 (peripheral neuritis and pernicious anaemia), Vitamin D, riboflavin, Iron, Calcium
and Zinc.

Positives of vegetarian lifestyles

• lower bodyweight, diabetes, blood pressure, arteriosclerosis, constipation and cancer

Negative of vegetarian lifestyles

• children filling up before eating
  enough protein for growth, women providing inadequately for foetal development and breast milk and women developing irregular menstruation

Question 15

Given the malnourishment in the world, do we need to be producing more food for the earth’s population?

Answer 15

No

One in seven people in the world are malnourished but the solution isn’t more food production but getting food to the right places

30-50% of the 4 billion metric tonnes of food produced globally each year becomes waste

Americans waste 40% of their food

Question 16

How much energy is required to be uptaken by the human adults?

Answer 16

For human adults the need for energy is
around 10MJ per day.

Less than this and we risk starvation, wasting and high rates of infection.

More than this and we risk obesity and a different set of disease conditions

Question 17

What does bomb calorimetry measure?

Answer 17

Bomb calorimetry gives a direct measure of the energy of combustion in food

It uses electrical ignition to produce the reaction:

Food + O₂ -> H₂O + CO₂ + N_xO_x + heat

The relative heat efficiencies / Atwater factors of common compounds:

Question 18

Discuss the energy content of alcohol and its usefulness as a fuel

Answer 18

Alcohol is an energy dense fuel -> 30 kJ of energy per gram of alcohol

Humans and cars carry out the same chemistry (by different means obviously) to get the exact same amount of energy from alcohol compounds:

alcohol + O₂ -> CO₂ + H₂0

Alcohol is converted to acetate in the human body. This acetate is capable of taking either of two pathways:

1. Burn it -> produce energy
2. Store it when have sufficient energy -> fat deposition

Question 19

What components of energy expenditure contribute to the 10 MJ energy requirement of the human diet?

Answer 19

1. Physical Activity = 20-40%
2. Temperature regulation / other = 2-4%
3. Specific Dynamic Effect (SDE) = 8-10%
4. Basal Metabolic Rate = 60%

Question 20

What is Specific Dynamic Effects (SDE)?

Answer 20

SDE is the energy expended in the absorption and transport of nutrient, digestive enzyme synthesis, gut mobility and gut replacement.

it is the energy involved in obtaining nutrients from food

8-10% of daily energy turnover

Also known as postprandial thermogenesis or heat increment of feeding

Question 21

What is the basal metabolic rate (BMR)?

Answer 21

BMR is the energy to pump blood, sustain cellular processes and the minimal metabolic activity to maintain 37 degrees.

It is the largest component of normal activity

It is measured strictly in subjects:

• at rest
• 12 hours after last meal
• in a thermoneutral environment of 25-30 degrees

Question 22

Is exercise an efficient consumer of daily energy?

Answer 22

Exercise is generally NOT a great a consumer of daily energy.

As a multiple of BMR sitting approximates to 1.2, Walking 3.2 and vigorous digging =6. Vigorous exercise is rarely sustained

Compared to the daily metabolic rate, exercise has relatively little effect on daily energy turnover

However, exercise is critical to health and weight regulation. Regular moderate exercise
of only 30 minutes a day protects against a range of diseases

Question 23

What benefits does exercise confer to the health of people?

Answer 23

Exercise improves:

• Health
• Cardiovascular fitness
• Cancer protection
• Bone strength
• Muscle strength
• Lung capacity
• Weight control

While also improving the immune system, nervous system, endocrine system and protection against cancers.

Question 24

How does BMR confer with body shape?

Answer 24

The BMR of humans and other mammals is dependent on body size and shape as a determinant of thermal efficiency

Surface area / Volume ratio is a determinant of BMR -> higher ratio is proportional to higher BMR

Compact bodies are more efficient – tall and skinny has a higher BMR and utilise more energy.

Large, sphereoid bodies shapes display greater conservation of energy due to less surface area.

Question 25

What effect does age, sex and body fat mass correspond to BMR?

Answer 25

Age

• Newborns use energy for growth -> have a relatively higher BMR to fuel this growth
• Adult BMR decreases by 2% every ten years after 20 y.o

High Body Fat

• Fat cells need little energy to store TAGs
• High fat = relatively low energy consumption and higher insulation against heat loss
• Most of the progressive adult BMR decrease results from fatty infiltration and replacement of muscle

Female vs Male

• Males have higher lean mass (lean mass = total mass -fat mass) and require ~1MJ more/day than females
  *

Question 26

Compare the relative amounts of BMR energy that each organ system demands

How does this differ between infants and adults?

Answer 26

Question 27

Discuss the change in eating habits in the USA over the last several decades

Answer 27

25% of all meals are eaten outside the home in USA

• Two thirds of all home meals are commercially pre-prepared

In Australia

• 48% of richest consumers and 52% of poorest consumers purchase pre-prepared meals regularly

People are eating bigger serves at each meal

Question 28

How does socioeconomic status relate to poor dieting?

Answer 28

The weight and shape of people is linked to the suburb in Melbourne where they live:

socioeconomic groups a huge factor

• Poor people spend more on food than high income earners as a percentage of income
• The poor tend to buy more unhealthier foods/eat more fast food
• Lower education status, sedentary life styles etc also correlate with obesity

Ethnicity is also a significant factor in susceptibilty to obesity and diabetes

Question 29

What is meant by the ‘set point’ of adipocytes?

Answer 29

Adipocytes are fat cells capable of varying their volume 20-fold to accomadate the elevated intake of dietary fats (expanding) or reduced intake of dietary fats (shrinking).

They don’t have any internal cytoskeleton -> allows them to alter cell volume.

There no limitation to the numbers of adipocytes that can be generated in adipose tissue -> virtually unlimited capacity to accomodate diet fat levels

The ‘set point’ of adipocytes means they tend to maintain a stable volume -> achieved by signalling to the brain to reduce food intake if increased fat deposition has occured and vice versa.

Question 30

What is leptin?

Answer 30

Leptin

• Leptin is produced by fat cells in direct proportion to the amount of stored energy/fat within them
• Studies show that in both humans and mice, a lack of leptin triggers a voracious appetite
  
  • When leptin levels return to normal - urge to eat goes away
• Most obese humans have high leptin levels but have become resistant to it due to down regulation of leptin receptors / pathways

Question 31

What is adiponectin?

Answer 31

**Adiponectin is a mixture anti-inflammatory peptide hormones secreted by adipocytes. **

Adiponectin stimulates the activation of AMP-activated kinase (AMPK) in skeletal muscle and liver

This upregulates:

• fatty-acid oxidation
• glucose uptake
• lactate production

and downregulates:

• gluconeogenesis in the liver

Adiponectin is a marker of metabolic syndrome - it is severely reduced in metabolic syndrome and obesity

Question 32

What is the role and function of ghrelin?

Answer 32

Blood concentrations of ghrelin fluctuate throughout the day, rising before a meal and then decreasing again upon consumption of a meal.

Ghrelin stimulates hunger in humans
by activating NPY/AgRP neurones in the
arcuate nucleus of the hypothalamus.

Food addiction in the obese may
relate to the separate action of ghrelin
on the addiction centre in the nucleus
accumbens.

Question 33

What some of the most impacting consequences of obesity in children and adolescents?

Answer 33

Complications of obesity in children

Psychosocial disorders

• Bullying, self confidence, body image

Precocious puberty

• Female children putting on fat that signals early onset of menstrual cycle to prepare for child rearing

Question 34

Describe the role of leptin in regulating food intake and energy usage

Answer 34

Leptin is a hormone that is secreted from adipocyte cells into plasma in proportion to BMI and fat

Leptin inhibits food intake by activating receptors in the hypothalamus. Activation of these receptors leads to the release of **anorexigenic neuropeptides **that decrease food intake and increase energy usage

Leptin has a transporter system to cross the BBB - meaning leptin levels crossing into the hypothalamus are **saturable. **

Leptin is also released in a circadian rhythm (highest levels at night to suppress food intake)

Question 35

How could abnormal leptin signalling contribute to obesity?

Answer 35

There are three ways abnormal leptin signalling could disrupt the energy expenditure/food intake balance that leads to obesity:

1. Unresponsive leptin receptors
2. Unresponsive second messengers from leptin receptor
3. Unresponsive transporter of insulin across the BBB

It could also be a result of decreased levels of leptin -> but this an *extremely rare condition *

Question 36

Discuss the use of Phentermine as an obesity drug

Answer 36

Phentermine is an amphetamine derivative that blocks the reuptake of NA, DA & 5-HT at the synapse -> thus increasing NA, DA & 5-HT available to bind to receptors

Is used as a short term drug (3 weeks) due to the rapid development of tolerance and addiction to it.

Adverse effects:

• Increased BP
• HR
• Insomnia
• Nervousness
• Headache
• Dry mouth

Cannot be combined with other weight loss drugs, antidepressants (MAO inhibitors), not safe in pregnancy

Question 37

Discuss Topiramate (Topamax) as an obesity drug

Answer 37

Topiramate (Topamax) is an “off-label” treatment of obesity; normally used in epilepsy and migraines

Mechanism is unknown

Increases energy expenditure and suppresses apetite

Used in patients BMI > 30

Adverse effects:

• dizziness
• taste alteration
• teratogenic

Question 38

Discuss the use of Orlistat as an obesity drug

Answer 38

Orlistat inhibits gastric and pancreating lipases -> prevents the breakdown of dietary TAGs into monoglycerides and FFA.

Dietary TAGs cannot cross the gut mucosa

Decreases dietary fat absorption by 30%

Shown to reduce:

• body weight andwaist circumference
• blood glucose
• insulin (Type 2 diabetes)
• dyslipidaemia
• blood pressure

Adverse effects:

• Mainly GIT complaints but controlled if adhere to low fat diet.
  
  • Include explosive diarrhoea and faecal fat leakage
• These adverse efffects are a behaviour modifying learning event for patients = forces them to adopt a low fat diet to avoid side effects

Must combine Orlistat treatment with a low fat diet & fat soluble vitamin supplementation (D & E) recommended

Question 39

List the designer characteristics that an effective obesity drug should have

Answer 39

1. Mechanism of action should be known
2. ** Reduce body weight** & associated medical complications
3. Benefits should outweigh the side-effects
4. No addictive properties
5. Should be able to use long-term
   * obesity is a life long illness