Nutrition: Hypothalamus and Eating Disorders

• Nutrition, Metabolism, and Etiology of Eating and Feeding Disorders

General Objectives

• Students will examine the relationship of the hypothalamus in feeding disorders.

Specific Objectives

• Discuss the hypothalamus functions.
• Evaluate how a patient with anorexia develops dysfunctions in organ systems based on the hypothalamic regulation of feeding and energy balance.
• Assess the pathogenesis of anorexia nervosa.

Hypothalamus

• Serves as the master regulatory center in the brain.
• Vital for survival and adapting to the environment
• Integrates sensory data and physiological signals related to short and long-term nutritional status to regulate eating behaviors.
• Processes sensory information via neurological and endocrine pathways in the arcuate nucleus, creating alternating states of hunger and satiety.
• Receives inputs from cortical areas, basal ganglia, and the brainstem.
• Sensitive to the levels of nutrients and hormones in the blood.
• Projects outputs to the pituitary gland, other brain areas, and the rest of the body via the autonomic nervous system.

Hypothalamic Functions

• Thirst and appetite regulation.
• Body temperature and sexual activity control.
• Sleep regulation.
• Shivering and perspiration.
• Heart rate and blood pressure maintenance.
• Regulation of reproduction
• Control of circadian rhythms
• Regulation of emergency response to stress
• Control of energy metabolism.

Hypothalamic Nuclei and Functions

• Paraventricular and Supraoptic Nuclei: Regulate water balance, produce ADH and oxytocin; destruction causes diabetes insipidus.
• Anterior Nucleus: Thermal regulation (dissipation of heat), stimulates parasympathetic NS; destruction results in hyperthermia.
• Preoptic Area: Contains sexually dimorphic nucleus; regulates release of gonadotropic hormones.
• Suprachiasmatic Nucleus: Receives input from the retina and controls circadian rhythms.
• Dorsomedial Nucleus: Stimulation results in obesity and savage behavior.
• Posterior Nucleus: Thermal regulation (conservation of heat); destruction results in an inability to thermoregulate.
• Lateral Nucleus: Stimulation induces eating; destruction results in starvation.
• Mammillary Body: Receives input from hippocampal formation and projects to the anterior nucleus of the thalamus.
• Ventromedial Nucleus: Functions as a satiety center with destruction resulting in obesity.
• Arcuate Nucleus: Produces hypothalamic releasing factors and contains DOPA-ergic neurons that inhibit prolactin release.

Hypothalamus Inputs and Outputs

• Afferent Information: Olfactory, gustatory, visual, auditory, tactile, and nociceptive sensors.
• Output: Influences the autonomic nervous system and the endocrine system in motivational drives.
• Monitors glucose, osmolality, sodium, hormone and cytokine levels.

Control of Energy Metabolism

• Energy Balance Homeostasis: Achieved by procuring food for metabolic needs and storing excess energy as fat for use during fasting.
• Excess caloric intake can lead to weight gain.

Hypothalamus

• Lesions in the lateral hypothalamic area cause aphagia (Feeding Center).
• Lesions in the ventromedial nucleus lead to obesity and hyperphagia (Satiety Center).

Insulin

• Stimulates beta cells to secrete insulin, lowering glucose levels.

Leptin

• Adipokine hormone secreted by adipocytes.
• Food intake up, temperature down, energy expenditure down, reproductive function down, parasympathetic activity up
• Food intake down, energy expenditure up, sympathetic activity up

Leptin and Insulin Action in the Hypothalamus

• The arcuate nucleus (ARC) integrates peripheral orexigenic and anorexigenic signals.
• Activation of neuropeptide Y (NPY).
• Agouti-related protein (AgRP) neurons in the ARC leads to decreased energy expenditure.
• Activation of proopiomelanocortin (POMC) neurons increases energy expenditure and decreases feeding behavior.

Energy Expenditure and Feeding Behavior

• Cell groups within the arcuate nucleus (ARC) integrate peripheral orexigenic and anorexigenic signals.
• Neuropeptide Y (NPY) activation decreases energy expenditure and increases feeding behavior.
• Proopiomelanocortin (POMC) activation increases energy expenditure and decreases feeding behavior.

Anorexigenic Neurons

• Decrease appetite
• Increase energy metabolism/ Weight loss

Orexigenic Neurons

• Increase appetite
• Decrease energy metabolism/Weight gain

Cholecystokinin

• Major hormone responsible for gallbladder contraction and pancreatic enzyme secretion, produced in the small intestines and CNS
• Acts on vagal afferent nerve fibres
• Sends signals to hinder brain to terminate meals/Satiety signals

Peptide YY

• Located in enteroendocrine cells of the ileum and colon and nerves of the enteric nervous system
• Inhibits gastric emptying and intestinal motility
• Signals to reduce food intake by activating POMC and CART in the Arcuate nucleus in the hypothalamus

Arcuate Nucleus

• Emotional stress and food intake influence hypothalamic activity.

Ghrelin

• Produced in the stomach.
• Increases during periods of fasting.
• Stimulates appetite.
• Leads to weight gain.
• Activation of reward centers in the hypothalamus, amygdala, and prefrontal cortex.

Hedonic Mechanisms Regulating Appetite and Satiety

• Food "liking" properties depend on opioid, cannabinoid, and GABA neurotransmission processed in the lateral hypothalamus (LH), nucleus accumbens (Nac), ventral pallidum, and insula.

Cortico-Striatal Pathways and Taste

• Chemoreceptors on the tongue detect a sweet taste, which is transmitted through the brainstem and thalamic taste centers, interconnecting with the anterior insula.
• The anterior insula is integral to a ventral (limbic) neurocircuit.

Cortical Structures and Taste

• Cortical structures involved in cognitive strategies send inputs to the dorsolateral striatum.

Taste Perception

• The sensory aspects of taste are primarily an insula phenomenon.
• Higher cortical areas modulate pleasure, motivation, and cognitive aspects of taste.

Myokines

• Involved in the anti-inflammatory effect of physical activity
• Counteract insulin resistance and metabolic perturbations in obesity and type 2 diabetes.
• A recently discovered myokine important in fat metabolism
• Secreted during exercise to improve energy balance
• Beneficial effects to obesity, insulin resistance, and inflammation
• Linked to a higher incidence of some cancers and positive effects on different types of cancers.

Epidemiology

• Lifetime Prevalence of Eating Disorders Among U.S. Adolescents (2001-2004):
  • Overall: 2.7%
  • Female: 3.8%
  • Male: 1.5%
• Lifetime Treatment of Eating Disorders Among U.S. Adults:
  • Anorexia Nervosa: 33.8%
  • Bulimia Nervosa: 43.2%
  • Binge-Eating Disorder: 43.6%
• Factors in etiology are Genetic, Psychological, Cultural/ Envirionmental, Biological and Neurobiological

General Eating Disorder Statistics

• 28-74% of risk for eating disorders is through genetic heritability.
• Eating disorders are lethal illnesses
• Economic cost of eating for disorders is $64.7 Billion a year

Psychological factors

• Anorexia: a stressful attempt to arrest development by using others comments about the individuals weight, negatively or positively.

Cultural Factors

• Anorexia nervosa is prevalent in post-industrialized, high-income countries
• Occupations with rigorous body shape control may contribute eating disorders by encouraging weight loss in extracurricular activities.

Biology

• Elevated in AN malnourished patients: Ghrelin
• Response to malnutrition: Normalised with weight gain

Leptin: Osteoporosis

• Starvation leads to high serum cortisol and low serum oestradiol, impacting bone mineralization.

Time Course and Phenomenology of Anorexia Nervosa

• Childhood personality traits: negative emotional expression, perfectionism, and a drive for a thinness
• A reduction in plasma levels of tryptophan (TRP) can lead to reduced negative emotions

Insula Response

• Altered taste processing may occur in AN, based on differences in activity in insular-striatal circuits
• Individuals with An process teste stimuli differently than controls, based on differences in neural activation patterns

Dopamine and Norepinephrine: Increase Energy

• During starvation the body increases activity to assist with obtaining food
• People with anorexia become hyperactive when fasting to increase dopamine levels
• Relives feelings of depression and reduce pain, and promote elation