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Endocrinology: Eating Behaviors

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Gabrielle Fundaro

on 7 May 2013

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Transcript of Endocrinology: Eating Behaviors

Endocannabinoids, Leptin, and Ghrelin:
Roles and Therapeutic Targets in Eating Disorders Background: Eating Disorders Background: ECB & Hunger Hormones Background: Eating Behavior Significance Abnormal eating behaviors
severe restriction
binge eating and vomiting (purging)
with or without drastic changes in body weight

Anorexia Nervosa (AN)
Bulimia Nervosa (BN)
Binge-Eating Disorder (BED)
Eating-Disorder Not Otherwise Specified (ED-NOS) What is hunger?


Homeostatic vs. Hedonic Anorexia has the highest fatality rate of any psychological or chronic childhood disease.
12.8% mortality rate
6% suicide rate

All patients with eating disorders experience some endocrine dysregulation in leptin, ghrelin, and ECB systems.

Understanding the endocrinology of eating disorders may lead to the development of more effective treatments. Gabrielle Fundaro
April 30, 2013
A la Palmiero Monteleone
Second University of Naples, Italy Ghrelin
Hunger-promoting gastric peptide released in anticipation of food intake
Leptin
Hunger-suppressing adipokine released in positive correlation with adiposity
Reciprocal relationship with AEA

Endocannabinoid System
Complex matrix of receptors and neurotransmitters that links the gut, brain, adipose tissue & pancreas
Include anandamide (AEA), 2-arachidonoylglycerol (2-AG), and cannabinoid receptors 1 and 2 (CB1/2) Food Intake Energy Expenditure Energy Balance Ghrelin Response to Eating
Effects of ghrelin:
DA release from NA
increased locomotor activity
activity of reward circuits
food consumption Reward System Integration www.atranik.org/the-limbic-system-and-the-reticular-formation Monteleone, 2012 Leptin Control of Food Intake Stoving, 2008 Effects of leptin:
degradation of anandamide
inhibition of orexigenic neuropeptides
stimulation of hypothalamic neurons producing anorexigenic neuropeptides Reward Behavior ECB System & Food Intake The presence of glucose and/or insulin increases levels of anandamide and 2-AG. Leptin has the opposite effect. Matias, 2006 Dysregulation: Ghrelin Monteleone P et al. JCEM 2008;93:4418-4421 Underweight females with AN experienced elevated basal plasma ghrelin & ratio of ghrelin to its anorexogenic precursor peptide

This does not correlate with increased food intake

No differences between controls and BN patients Dysregulation: Ghrelin Psychoneuroendocrinology Volume 35, Issue 2 2010 284 - 288 Palmiero Monteleone , Cristina Serritella , Pasquale Scognamiglio , Mario Maj Biological Psychiatry Volume 64, Issue 11 2008 1005 - 1008 Palmiero Monteleone , Cristina Serritella , Vassilis Martiadis , Mario Maj Both patients with AN and BN experience derangement in plasma ghrelin during cephalic phase

Patients with AN experiences higher levels than those of patients with BN Dysregulation: Leptin Monteleone, et al. Mol Psychiatry. 2002;7(6):641-6. Outline Background
Eating Behavior
Hunger Hormones
Eating Disorders
Significance
Dysregulation
Ghrelin
Leptin
Endocannabinoids
Therapies
Conclusions, Limitations & Future Directions Female patients with BN or AN showed reduced levels of plasma leptin

Soluble leptin receptor (OB-R) expression was significantly increased in patients with BN or AN

Levels in obese women with or without BED opposed those of AN or BN patients Dysregulation: Leptin Monteleone, et al. Psychosom Med. 2002 Nov-Dec;64(6):874-9. Healthy women have varied levels of leptin. Late-stage BN patients experience hypoleptinemia similar to AN even without changes in body fat. Dysregulation: Endocannabinoids Monteleone, et al. Neuropsychopharmacology. 2005 Jun;30(6):1216-21. Despite existing at opposing ends of the ED spectrum, patients with AN or BED had significantly elevated levels of plasma AEA. Dysregulation: Endocannabinoids Healthy AN Patients Leptin and AEA exhibit a significant negative correlation in healthy individuals and AN patients. Monteleone, et al. Neuropsychopharmacology. 2005 Jun;30(6):1216-21. Food Restriction/
Hyperactivity Loss of Body Fat Decreased Leptin, Increased Ghrelin & AEA Increased Reward Behavior Anorexia Hedonic Eating Ghrelin Dysregulation Hypoleptinemia in BN Increased Reward Behavior Bulimia/BED Increased AEA in BED Therapies Goals:
restore normal eating behaviors
recover healthy BMI
improve perception of self
restore menstruation
reduce hyperactivity
prevent hyperleptinemia

Methods: CBT, hospitalization & refeeding, atypical antipsychotics, i.v. ghrelin, exogenous eCB, monitoring/increasing leptin levels eCB's:
released from hypothalamus to interact with limbic DA pathway & mediate ghrelin/leptin release Ghrelin 1ug/kg bolus injx in humans increased hunger

5 hr infusion of 5pmol/kg/min did not affect appetite

3ug/kg 2x per day for 14 days increased EI and hunger Leptin Leptin administration prevented/ceased fasting-induced hyperactivity in rodents

In humans, administration improved self-perception

Athletic amenorrhea can be abrogated eCB's Supplementation in mice increases EI at low doses

EI is not affected at high doses but hyperactivity is reduced

THC administration in humans improved self-perception with no change in BW eCB's & Refeeding Verty, et al. Neuropsychopharmacology. 2011 June; 36(7): 1349–1358. Refeeding with a HFD prevents weight loss in rodent models of activity-based AN with reductions in FAO. Limitations Patients must be motivated to recover.
Many experience GI upset with refeeding.

Ghrelin
preproghrelin v. ghrelin measurements differ
increased reward behavior
perception of hunger in healthy vs. AN
Leptin
hyperleptinemia reduces hunger during AN recovery due to increased OB-r
eCB's
levels already elevated in AN patients
no evidence for improved body condition Conclusions &
Future Directions CBT is essential to improve intrinsic motivation
HFD & eCB's appears most effective in ameliorating weight loss
Ghrelin appears most effective in improving EI

More research is needed to determine the effectiveness of a holistic approach utilizing ghrelin, eCB's, and CBT. Thank You

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