Eating Disorders: Hypothalamus Role

• The topic is Nutrition, Metabolism, and Etiology of Eating and Feeding Disorders

General Objective

• The hypothalamus plays a key role in feeding disorders

Specific Objectives

• Hypothalamus functions should be discussed as an overview
• Evaluate organ system dysfunctions in anorexia patients based on hypothalamic regulation of feeding and energy balance
• Assess the pathogenesis of anorexia nervosa

Hypothalamus

• Vital for survival and adapting to the environment
• Is the primary regulation center in the brain
• Integrates various data like sensory and physiological relating to short and long term nutritional status to regulate eating behaviours
• Sensory data is transmitted via neurological and endocrine pathways
• The arcuate nucleus primarily processes the data and helps create alternating states of hunger and satiety
• The hypothalamus receives input from cortical areas, basal ganglia, and the brainstem
• Sensitive to levels of nutrients and hormones in blood
• Projects outputs to the pituitary gland, other brain areas, and through the autonomic nervous system, to the rest of the body
• Regulates thirst, appetite, body temperature, sexual activity, sleep, shivering, perspiration, heart rate, and blood pressure
• It controls energy metabolism by procuring food for metabolic needs and storing excess energy as fat for fasting periods

Hypothalamus Afferent Information

• Olfactory
• Gustatory
• Visual
• Auditory
• Tactile
• Nocioceptive sensors

Hypothalamus Output

• Autonomic nervous system
• Endocrine system
• Motivational

Hypothalamus Output Signals

• Glucose
• Osmolality
• Sodium
• Hormones -Cytokines

Nuclei of the Hypothalamus Functions

• Paraventricular nucleus regulates water balance and stress
• Supraoptic nucleus regulates water balance
• Anterior nucleus regulates blood pressure
• Medial Preoptic regulates body temperature
• Lateral hypothalamic area, feeding center lesions cause aphagia
• Dorsomedial hypothalamic area (DMT)
• Posterior hypothalamic area regulates shivering
• Ventromedial nucleus (satiety) lesions cause obesity and hyperphagia
• Suprachiasmatic regulates biological clock
• Mammillary body (feeding)

Insulin

• Insulin stimulates cellular uptake of glucose
• Insulin stimulates the storage of glucose as glycogen or adipose tissue
• Stimulates beta cells to secrete insulin, it lowers blood glucose
• Glucagon stimulates the noncarbohydrate conversion of glucose
• Glucagon stimulates the conversion of glycogen to glucose
• Alpha cells are stimulated to secrete glucagon when blood glucose levels are low

Leptin

• It is an adipokine, a hormone secreted by adipocytes
• Food intake ↑, Temperature ↓, Energy Expenditure ↓, Reproductive Function ↓, Parasympathetic activity ↑ when leptin levels fall
• Food intake ↓, Energy Expenditure ↑, Sympathetic activity ↑ when leptin levels rise

Control of Energy Expenditure and Feeding Behavior

• Cell groups within the arcuate nucleus (ARC) integrate peripheral orexigenic and anorexigenic signals
• Activating neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons within the ARC decrease energy expenditure by acting via the paraventricular nucleus of the hypothalamus (PVH), the pituitary, and the nervous system
• The above increases feeding behavior by acting via the lateral hypothalamic area (LH) and other central nervous system (CNS) sites
• Activation of proopiomelanocortin (POMC) neurons within the ARC increases energy expenditure and decreases feeding behavior acting via the same areas
• Peripheral signals activate the brainstem via the vagus nerve; the brainstem then bypasses the ARC to act directly on the PVH and LH

Anorexigenic Neurons

• Decreases appetite
• Increases energy metabolism
• Leads to weight loss

Orexigenic Neurons

• Increases appetite
• Decreases energy metabolism
• Leads to weight gain

Energy Metabolism and Gut Hormones: Cholecystokinin

• Major hormone responsible for gallbladder contraction and pancreatic enzyme secretion
• Produced in the small intestines and CNS
• Acts on vagal afferent nerve fibers, sends signals to dorsal hindbrain to terminate meal, resulting in satiety

Energy Metabolism and Gut Hormones: Peptide YY

• Found in enteroendocrine cells of the ileum and colon and nerves of the enteric nervous system
• Inhibits gastric emptying and intestinal motility to delay more food to the intestine
• PYY sends signals to the brain to reduce food intake by activating the POMC and CART in the Arcuate nucleus in the hypothalamus

Arcuate Nucleus Signaling

• Emotional stress and food intake affects the Nucleus

Energy Metabolism and Gut Hormones: Ghrelin

• Produced in the stomach and increases during fasting or conditions associated with negative energy balance such as starvation, or in hyperglycemia and obesity
• Decreases after eating
• Stimulates appetite, induces a positive energy balance, and can lead to weight gain
• Increases number, but not size of meals
• Elevated fasting levels activate reward centers in the hypothalamus, amygdala, and prefrontal cortex, indicating that food consumption is more complicated than hunger/satiety

Hedonic Mechanisms

• The hedonic (liking) properties of food are partially dependent on opioid, cannabinoid and GABA neurotransmission
• These are processed in the lateral hypothalamus (LH), Nucleus accumbens (Nac), ventral pallidum and insula

Cortico-Striatal Pathways Involved in Taste

• Chemoreceptors on the tongue detect sweet taste
• Signals are transmitted through the brainstem and thalamic taste centers in the primary gustatory cortex
• Connected with the anterior insula
• The anterior insula is an integral part of a 'ventral (limbic) neurocircuit' through its connections with amygdala, anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC)
• Structures involved in the ventral neurocircuit direct afferents to the ventral striatum

Cortico-Striatal Pathways with Focus in Taste

• Cortical structures involved in cognitive strategies send inputs to the dorsolateral striatum
• The sensory aspects of taste are primarily an insula phenomenon
• Higher cortical areas modulate pleasure, motivation and cognitive aspects of taste
• All aspects are integrated and result in decision of whether or not to eat

Myokines

• Involved in the anti-inflammatory effect of physical activity
• Critically counteract insulin resistance and metabolic perturbations of obesity and type 2 diabetes
• Irisin is a myokine that plays a role in fat metabolism through the browning of white adipose tissue
• Secreted after exercise to improve energy balance
• Potential as a treatment for metabolic diseases like obesity, insulin resistance, and inflammation
• Higher incidence of some cancers are linked to Obesity
• Some studies shown irisin to have direct positive effects on different types of cancers

Epidemiology Statistics

• 28-74% of the risk for eating disorders is through genetic heritability
• Eating disorders are highly lethal, second only to opioid overdose
• 10,200 annual deaths are a direct result of an eating disorder
• About 26% of people with eating disorders attempt suicide
• The economic cost is $64.7 billion every year

Black, Indigenous, and People of Color (BIPOC) Eating Disorder Statistics

• BIPOC are less likely than white people to have been asked by a doctor about eating disorder symptoms or receive treatment
• Black people are less likely to be diagnosed with anorexia nervosa than white people but may be ill for a longer period of time
• Black teenagers are 50% more likely than white teenagers to exhibit bulimic behavior like binge-eating and purging
• Hispanic people are significantly more likely to suffer from bulimia nervosa than their non-Hispanic peers

LGBTQ+ Eating Disorder Statistics

• Gay and bisexual boys are more likely to fast, vomit, or take diet pills to control weight
• Gay men are seven times more likely to report binge-eating and twelve times more likely to report purging than heterosexual men. 32% of transgender people report using their eating disorder to modify their body without hormones

Etiology of Eating Disorders

• Genetic
• Psychological
• Cultural/Environmental
• Biological
• Neurobiological

Psychological factors: Anorexia

• Attempt to arrest development
• Idealized slimness
• Positive comments about initial weight loss
• Negative comments from others about weight
• Stressful life situation
• Childhood anxiety and obsessiveness

Cultural Factors Associated with Anorexia Nervosa

• Historical and cross-cultural variability in the prevalence supports association with cultures/settings where thinness is valued
• Most prevalent in postindustrialized and high-income countries, many European states, Australia, New Zealand, Japan, and the United States
• Overrepresented in occupations requiring rigorous control of body shape
• Weight loss encouraged in extracurricular activities by coaches, parents, and professionals may inadvertently contribute

Biology: Ghrelin

• Elevated in anorexia nervosa malnourished patients
• Normalized with weight gain
• Response to malnutrition

Biology: Leptin with Osteoporosis

• Accompanied by high serum cortisol during starvation, which enhances bone resorption, and low serum concentrations of oestradiol, an important hormone for bone mineralization
• Low leptin levels have an indirect effect on bone density via relevance for the hyphotalamic-pituitary-gonadal axis
• In anorexia nervosa, leptin levels are low and increase with weight gain
• Low leptin levels shut off the hypothalamic-pituitary-gonadal axis, which results in amenorrhea

Time Course and Phenomenology of Anorexia Nervosa

• Childhood personality and temperament traits contribute to vulnerability of developing anorexia nervosa (AN)
• Intensified during adolescence because of puberty, steroids, development, stress, and culture
• Dieting reduces and eating enhances dysphoric mood in individuals with anorexia nervosa (AN)
• With chronic dieting and weight loss, neurobiological changes increase denial, rigidity and obsessions, as well as depression and anxiety and patients often enter a downward spiral

Role of Serotonin in Anorexia Nervosa

• Elevated Serotonin
• Reduction of Plasma Levels of Tryptophan (TRP) which lessen Symptoms of Dysphoric Mood
• Patients restrict food intake in order to reduce anxiety and dysphoric mood states
• Reduction in anxiety, but difficulty with sleep and decrease memory

Insula Response in Patients Recovered of Anorexia Nervosa (AN)

• Individuals show a significantly lower neural activation of the insula, which processes positive or negative valuation of stimuli
• Altered taste processing occurs based on differences in activity in insular-striatal circuits
• Individuals with AN process taste stimuli differently from controls

Imbalance Between Interoceptive and Rewarding Processing in Anorexia Nervosa

• AN patients experience a strong conflict between the biological need for food and the acquired averse association with food, causing negative valuation
• Altered interoceptive valuation affect the striatal responses, shifting the behavioral toward patient avoiding food, and staying thin
• In healthy individuals, food-related stimuli ascending interoceptive afferents converge on the anterior insula which processes state-related positive valuation
• This information in healthy individuals converges in the striatum receiving inputs from the anterior insula and prefrontal cortex

Dopamine + Norepinephrine (NE)

• The Evolutionary Mechanism
• Eating and NE levels increase by exercise so the patient doesn't feel so hungry and will feel more satisfied
• Stress (with low self esteem, social rejection), DA + NE decreases which lead to not eat; in the other hand normal food to the patient the level will be normal