Flashcards in Lecture 48-49: Eating Deck (67):
Diagnostic criteria for anorexia nervosa (4)
1. Body weight
Diagnostic criteria for bulimia (4)
1. Binge eating (loss of control); 2. Purging; 3. Over-concern with body weight; 4. Weight can be normal, high, low
How common are genetic disorders that cause morbid obesity? Name one target for such a mutation
Very rare; leptin/leptin receptor
What is genetic component (%) of obesity risk? Health risk what what BMI?
What is the best obesity "hit" from GWAS studies?
FTO gene (DNA/RNA demethylase); 16% of adults are homozygous for obesity-causing gene
A lesion where causes animals to stop eating (orexigenic region)?
Lateral hypothalamus (LH)
A lesion where causes animals to become obese (anorexigenic region)?
Medial hypothalamus (MH)
Neural circuits involved in feeding (3)
1. Hypothalamus (physiological need for food); 2. Mesolimbic DA system (desire for food as rewarding); 3. Cerebral cortex (control)
Which neurobiological system mediates hunger?
Which neurobiological system mediates appetite?
Mesolimbic DA system
Which neurobiological system integrates psychological/social factors with feeding behavior?
Leptin increases/decreases food intake. What else does it do? (2)
Decreases; increases energy use and sympathetic tone
What makes leptin? What kind of molecule?
Adipose tissue; small peptide
Leptin does what to orexigenic factors?
Where does leptin produce its effect? What kind of receptor does leptin use? Final effect of signal transduction?
Hypothalamus; protein kinase; TFs
T/F: Leptin levels explain common obesity? Explain.
False! Heavy people DO have higher leptin levels
What is leptin's primary site of action (structure and nucleus)
Hypothalamus: arcuate nucleus
Orexigenic factors: Neuropeptide Y (NPY), Agouti-related peptide (AgRP)
Anorexigenic factors: alpha-Melanocyte-stimulating hormone (a-MSH); CART
Leptin is able to stimulate the hypothalamus because?
Lack of BBB
Arcuate nucleus projects to...
Lateral and medial hypothalamus
Medial hypothalmus factors
Anorexigenic: CRF, TRF
Laterial hypothalmus factors
Neuropeptide Y does what?
Neuropeptide Y neurons in arcuate nucleus project
to medial hypothalamus (PVN), where they inhibit anorexigenic peptides (CRF), and to lateral hypothalamus, where they stimulate orexigenic peptides (MCH)
In general, all orexigenic peptides are Gi/Gs-linked? Anorexigenic?
Gi-linked, while anorexigenic peptides are Gs-linked
Melanocortin is an/orexigenic? What is a natural antagonist for Melanocortin receptor?
What is the strongest orexigenic factor?
Melanin-Concentrating Hormone is expressed where? An/orexigenic?
Lateral hypothalamus; orexigenic
CRF and TRF are expressed where. An/orexigenic?
PVN in medial hypothalamus; anorexigenic
CART is expressed where. An/orexigenic?
Arcuate nucleus of hypothalamus and lateral hypothalamus; anorexigenic
Orexin produces pro-/anti-feeding effects
The full action of insulin and glucose require what?
The brain! Via the hypothalamus
Describe Ghrelin: where it's secreted, when, an/orexigenic; targets (2)
Stomach; during fasting; orexigenic; NPY/AgRP neurons AND reward neurons
Describe Glucagon-like peptide 1 (GLP1): where it's secreted, when, an/orexigenic; target
Intestinal L cells; during feeding; anorexigenic (promotes insulin/reduces glucacon); mainly acts in periphery
What hormone has been used in drug development?
GLP1 peptide agonist (Exenatid)
What is a surgical treatment for obesity? Name serious adverse events (2)
Bariatric surgery; malabsorption/metabolic syndromes and depression
T/F: Feeding peptides innervate VTA-NAc pathway. Explain
True! Via hypothalamic-VTA and NAc pathway
Agents that enhance serotonin function do what to appetite? What is the proposed receptor? Knockout mice for this receptor...
Suppression; 5HT2c receptor; develop obesity
Cannabinoid-related drugs for obesity would do what? Problems with these drugs.
CB1 antagonist; linked to depression/suicide
Is there a role of leptin in anorexia?
Genetic contribution to anorexia/bulimia (%)
Eating disorders (4)
Anorexia nervosa, bulimia nervosa, binge eating disorder, eating disorder not otherwise specified
Gender disparity in anorexia and bulimia
Aorexia = 10 : 1; bulimia = 5 : 1
Core symptoms of eating disorders (3) w/ description
1. Eating disturbances (PRIMARY symptom = too little, binging, or overeating); 2. Dietary restraint (can be either intention or behavior); 3. Body image disturbance (over-evaluation in shape/weight)
Name and define two types of binges
Subjective binge: patient may consider "binge" but is normal amount of food; Objective binge: abnormally large amount of food w/ an out of control feeling
Evaluation of shape and weight includes which two behaviors?
1. Avoidance; 2. Checking
Three personality/risk factors for eating disorders
1. Picky eating; 2. Perfectionism; 3. Harm avoidance
The course of anorexia begins with...what does this cause?
A diet/large loss of weight; stress --> decrease of HPG axis (lower LH, FSH, leptin AND increased Peptide Y, ghrelin, eCB system)
Even after re-achieving a healthy weight, what are long-term effects of anorexia?
Continued HPG, serotenergic and eCB system dysregulation
Relapse rate for anorexia (%)
Mortality for anorexia (%)
In anorexia, signals for appetite might be high, so why isn't there an appropriate response?
Sensitization: constantly high appetite signals "burn-out" the receptors (etc), decreasing the appropriate response
Harm avoidance is characterized by which two traits and is related to which NT system?
(+) error detection and inhibition in response to uncertainty; Dysregulation of 5HT system
How is harm avoidance affected by ovarian hormone surge?
Increase in dysphoric mood, error detection, inhibition in response to uncertainty
Initial starvation does what to ovarian hormone surge? This is what stage of anorexia?
Decreases it --> temporary relief; Early State AN
Describe late stage AN
Continued decrease in 5HT --> dyphoric mood and stress adaptations
Describe problems with re-feeding
Re-feeding leads to more 5-HT (via tryptophan) and very high levels of dysphoria, error detection, inhibition response to uncertainty
Prolonged periods of starvation impacts brain volume...
Loss of volume (mostly in gray matter) but it returns post-weight restoration (insula may be one exception)
Heritability for anorexia (%)
First-line treatment for anorexia
Family based therapy
Medications for anorexia?
None outperform placebo
Binge-purge cycle for negative reinforcers
Negative emotional state --> over eat (feel better) --> negative appraisal/loss of control --> compensatory behavior (binge) --> dietary control --> hedonia and vulnerability to environmental stress
Binge-purge cycle for positive reinforcers
Novelty, pleasure seeking/impulsivity --> overating --> neg appraisal --> neg emotional state --> hedonic drive to increase pleasure
Bulimia involves which two personality types
Cluster C: perfectionism, harm avoidant; Cluster B: novelty seeking, impulsive
Treatments for bulimia nervosa (4)
1. CBT (most robust); 2. Interpersonal therapy; 3. Guided self-help; 4. Medication (SSRIs)
Over all, how effective are bulimia treatments?
About 40% remission/reduction