3.4 Investigating energy balance stressors

Between which two things is an energy balance?

Between energy intake and energy expenditure.

What 3 (food) sources are involved in energy intake?

• Carbohydrate;

• Protein;

• Fat.

What 3 elements are involved in energy expenditure?

• Resting metabolic rate;

• Thermic effect;

• Active energy expenditure.

How does the body show an equilibrium in energy intake and energy expenditure? Name 2 examples.

• When you consume more calories than you needed, than your body tells you that you are stuffed.

• When you consume less calories than you needed, than your body tells you that you are hungry. You body gives you feedback that you have to eat

Name an example of a condition that causes energy balance disturbances over the whole equilibrium?

Anorexia is at the whole end of a negative balans.

What is anorexia nervosa (AN)?

A (metabo) psychiatric disorder characterised by fear of weight gain and dangerously low body weight. The mortality rate is higher than for other mental disorders and treatment is on a standstill. It is a complex, heritable, multifactorial condition, with a genetic basis estimated to be 28-74%. Genetic correlations correspond with observations of comorbidity.

What are risk factors for AN?

• Biological: sex, age, ethnicity, sexual development, gut microbia composition

• Psychological: anxiety, depression, perfectionism, low self-esteem, obsessive-compulsive disorder

• Environmental and social: lifestyle and diet, social networks, adverse familiar environment, historical trauma, media influence and beauty standards

• Genetic and epigenetic: genome-wide significant loci

What is the neurocircuit of anorexia in rodents?

Amygdala, ventral striatum, ARC, PBN

What is meant by an Activity-Based Anorexia (ABA) model?

These mouse models don’t have anorexia, but they only show some symptoms of anorexia?

What are 2 elements of the Activity-Based Anorexia (ABA) model?

• Time restricitive feeding (eating at certain moments will lead to the presentation of a strong stimulus)

• Wheel accessible 24/7.

What is correlated to anxiety in the ABA model?

Before a meal, there is a large increase of activity.

What is meant by ad libium?

Eating and drinking 24/7

What is the difference between ad libium rodents and rodents that eat less in a day?

Ad libium rodents have a lower activity. The less they get to eat, the more they move.

What is meant by food anticipatory activity (FAA)?

This is when the wheel-running activity of mice decreases after feeding, and then rapidly increases in the hours leading up to feeding.

What was the outcome of the FAA study?

Bodyweight for ABA en Sed. Control (ABA without wheel) is much lower dan for the controle mice, but ABA has a lower weight than Sed. control. Moreover, food intake for ABA en Sed. Control is much lower than for controle mice. Lastly, wheel running is for ABA much lower than for control group.

Conclusion: body weight is not only dependent on the food intake, but also on the amount of movement.

What levels are low in anorexia patients?

Leptin levels

How are the leptin levels in anorexia treatment, before, during and after treatment?

• Before treatment: low levels

• During treatment: high levels

• After treatment: relapse and low levels

What do leptin injection in ABA models give?

Good results

What is the effect of sc. administration of leptin in anorexia nervosa patients?

It results in intermittent supraphysiological leptin plasma levels partially. It has an influence on clinical symptoms, but also on neuro-endocrine regulation.

How does targeted recombination in active populations (TRAP2) work using a cre-loxP system?

You will remove the stop codon and then a fluorescent gene can be read. Neurons that are active by a specific behaviour will then colour red.

What are DREADs?

Molecular on and off switches; they use an artificial receptor that does not influence the human body, but something in the body influences the receptor wherefore it gets activated. Therefore, they become activated with administration of CNO.

What factors are used in modulating ABA ensembles?

Viral factors that have these factors inverse in brain regions.

How dus modulating ABA ensembles?

Inject DREAD in hunger center → inject hunger hormon ghrelin → neurons that are active when injecting that hormone have the receptor → now you can neurons setting on and off here → look at function of these neurons

How can we manipulate behaviour?

Using Cre-loxP systems and chemogenetics.