Hypothalamus & Feeding Disorders

• General objective is examining the relationship between the hypothalamus and feeding disorders.

Specific Objectives

• Understanding of the hypothalamus functions.
• Evaluating organ system dysfunctions in anorexia patients based on hypothalamic regulation.
• Assessing the pathogenesis of anorexia nervosa.

Hypothalamus Functions

• Integrates information to regulate eating behaviors, including sensory data and physiological signals related to short and long-term nutritional status.
• Processes sensory information via neurological and endocrine pathways in the arcuate nucleus, creating hunger and satiety states.
• Receives inputs form cortical areas, the basal ganglia, and the brainstem.
• Relays outputs to the pituitary gland, other brain areas, and the rest of the body via the autonomic nervous system.
• Regulates thirst, appetite, body temperature, sexual activity, and sleep & wake cycles.
• Controls the circadian rhythms and energy metabolism.
• Regulates reproduction and emergency responses to stress.
• Control of body fluids.
• Involved in water balance, producing ADH and oxytocin.
• Anterior nucleus is involved in thermal regulation.
• The preoptic area regulates the release of gonadotropic hormones.
• The suprachiasmatic nucleus receives retinal input and controls circadian rhythms.
• The dorsomedial nucleus, when stimulated, leads to obesity and savage behavior.
• The posterior nucleus regulates temperature through heat conservation.
• The lateral nucleus when lesioned results in starvation.
• The ventromedial nucleus is the satiety center.

Information Flow in the Hypothalamus

• Afferent Information includes:
  • Olfactory, Gustatory, Visual, Auditory, Tactile, and Nocioceptive sensors
• Output functions:
  • Autonomic nervous system, Endocrine system, and Motivational
• Influenced by:
  • Glucose, Osmolality, Sodium, Hormones, and Cytokines

Energy Metabolism

• The hypothalamus controls energy metabolism by procuring food, storing excess energy as fat, and balancing energy homeostasis.
• A small caloric excess of 10 kilocalories/day, less than 1%, can lead to an annual weight gain of about 1 pound (0.45 kg).

Hypothalamic Nuclei

• Lesions in the feeding center will cause aphagia.
• Lesions in the satiety center will result in obesity and hyperphagia.

Insulin and Glucostatic Theory

• The body reacts via insulin secretion when glucose levels increase, and glucagon secretion when dropping.
• Normal blood glucose is 75-115mg/dL

Leptin

• Leptin is an adipokine secreted by adipocytes.
• It increases food intake, decreases temperature and energy expenditure, reduces reproductive function and stimulates parasympathetic activity.
• Increases food intake, stimulates energy expenditure, and increases sympathetic activity

Arcuate Nucleus (ARC) Role

• It integrates orexigenic and anorexigenic signals.
• NPY/AgRP activation decreases energy expenditure while increasing feeding behavior.
• POMC activation increases energy expenditure while decreasing feeding behavior.
• Additional peripheral signals activate the brainstem via the vagus nerve, bypassing the ARC and acting directly on the PVH and LH.

Neurons and Feeding Behavior

• Anorexigenic neurons: - Decrease appetite - Increase energy metabolism, resulting in weight loss
• Orexigenic neurons: - Increase appetite - Decrease energy metabolism, resulting in weight gain

Gut Hormones

• Cholecystokinin (CCK):
  • Major hormone responsible for gallbladder contraction and pancreatic enzyme secretion
  • Produced in the small intestines and CNS
  • Acts on vagal afferent nerve fibers, signaling the dorsal hindbrain to terminate meals, inducing satiety
• 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 the brain to reduce food intake by activating POMC and CART in the Arcuate nucleus of the hypothalamus
• Ghrelin:
  • Produced in the stomach and increases during fasting
  • Decreases after eating or with hyperglycemia, and in obesity
  • Stimulates appetite and induces a positive energy balance
  • Increases the number, but not the size of meals.
  • Elevated fasting levels activate reward centers, indicating food consumption involves factors beyond hunger and satiety

Hedonic Mechanisms

• Food liking is influenced by opioid, cannabinoid, and GABA neurotransmission.
• This is processed in the hypothalamus, Nucleus Accumbens, ventral pallidum and insula.

Cortico-Striatal Pathways

• Chemoreceptors on the tongue detect sweet taste signals through the brainstem.
• Signals pass through thalamic taste centers in the primary gustatory cortex, which are interconnected with the anterior insula.
• The Cortical structures direct signals to the ventral striatum, modulating the decision to eat or abstain.
• Higher Cortical Areas modulate Pleasure, motivation and cognition.
• Cortical structures involved in cognitive strategies send inputs to the dorsolateral striatum

Health

• Myokines, released during physical activity, counteract insulin resistance and metabolic perturbations.
• Irisin is a myokine that improves fat metabolism and may benefit metabolic diseases.

Epidemiology of Eating Disorders

• Lifetime prevalence among U.S. adolescents (2001-2004): is 2.7% overall, 3.8% in females, and 1.5% in males.
• Genetic heritability accounts for 28-74% of the risk.
• Eating disorders are lethal.
• 10,200 yearly deaths directly result from eating disorders.
• Roughly 26% of individuals with eating disorders attempt suicide.
• Economic impact of eating disorders reached $64.7 billion annually.
• BIPOC are less likely to be asked about eating disorder symptoms or receive treatment.
• Black individuals are diagnosed less with anorexia nervosa.
• Black teenagers are more likely to show bulimic behaviors.
• Hispanic people are more likely to suffer from bulimia nervosa than their non-Hispanic peers.
• Gay/bisexual boys are more likely to use extreme weight control methods.
• Gay men are more likely to report binge-eating and purging.
• About 32% of transgender people use their eating disorder to modify their body without hormones.

Etiology of Anorexia

• Can involve psychological factors, such as an attempt to arrest development or negative comments from others about weight.
• Historical and cross-cultural variability in the prevalence of anorexia nervosa supports its association with cultures and settings that value thinness.
• Leptin levels are low in patients with anorexia but increasing weight brings them up, which shuts down the hypothalamic-pituitary-gonadal axis, leading to amenorrhea.
• AN traits become intensified during adolescence because of the effects of multiple factors, such as puberty and gonadal steroids, development, stress and culture.

Serotonin Role

• High serotonin contributes to characteristic anxiety and obsessionality.
• Dieting behavior and food restriction decreases serotonin activity.
• High dopamine and norepinephrine from exercise relieves depression, irritability and pain.

Insula Response

• Individuals recovered from showed a significantly lower neural activation of the insula and the primary cortical taste region.
• Suggesting Individuals process taste stimuli differently than control.

Imbalance

• Anorexia nervosa patients often experience a conflict between biological needs and an aversion to food.
• Excessive cognitive control in anorexic shifts the behavioral event horizon towards satisfying long-term goals rather than to satisfy short-term goals avoiding food.