Hunger and satiety are complex processes controlled by the brain, particularly the hypothalamus. These mechanisms involve hormones like ghrelin, which stimulates appetite, and leptin, which suppresses it. Understanding these signals is crucial for grasping how our bodies regulate eating behaviors.

The interplay between short-term and long-term satiety signals influences our eating patterns. Short-term signals from the gut, like CCK, affect individual meals. Long-term signals, such as leptin, regulate overall energy balance. This system helps maintain homeostasis in our eating behaviors.

Hypothalamus in Hunger Regulation

Hypothalamic Regions and Neurons

• Lateral hypothalamus contains neurons stimulating feeding behavior when activated (feeding center)
• Ventromedial hypothalamus contains neurons suppressing appetite when activated (satiety center)
• Arcuate nucleus of the hypothalamus contains two distinct neuron populations
  • NPY/AgRP neurons stimulate feeding
  • POMC/CART neurons inhibit feeding
• Lesions or stimulation of specific hypothalamic regions dramatically alter feeding behavior and body weight regulation

Hypothalamic Integration and Communication

• Hypothalamus integrates various hormonal and neural signals from the periphery to modulate hunger and satiety
• Communicates with other brain regions to influence overall feeding behavior
  • Brainstem involvement in autonomic control of digestion
  • Cortex involvement in food-related decision-making (food choices, portion sizes)
• Processes multiple inputs to coordinate appropriate hunger and satiety responses
  • Hormonal signals (ghrelin, leptin, insulin)
  • Neural inputs (vagal afferents from the gastrointestinal tract)
  • Metabolic signals (glucose levels, fatty acids)

Ghrelin and Leptin in Appetite

Ghrelin: The Hunger Hormone

• Primarily produced by the stomach, stimulates appetite and promotes food intake
• Levels typically increase before meals and decrease after eating (short-term hunger signal)
• Acts on the hypothalamus, particularly activating NPY/AgRP neurons in the arcuate nucleus
• Influences meal initiation and frequency
• Example: Ghrelin levels rise before typical mealtimes, even in the absence of food cues
• Example: Individuals with Prader-Willi syndrome have abnormally high ghrelin levels, contributing to excessive hunger

Leptin: The Satiety Hormone

• Produced by adipose tissue, acts as a long-term signal of energy stores and suppresses appetite
• Levels generally proportional to body fat mass (higher in individuals with more adipose tissue)
• Acts on the hypothalamus, activating POMC/CART neurons in the arcuate nucleus
• Regulates long-term energy balance and body weight
• Leptin resistance can occur in obesity, leading to leptin insensitivity despite high circulating levels
• Example: Individuals with congenital leptin deficiency experience extreme obesity and hyperphagia
• Example: Weight loss leads to decreased leptin levels, contributing to increased hunger and difficulty maintaining weight loss

Homeostatic Hunger

Physiological Mechanisms

• Glucose-fatty acid cycle (Randle cycle) regulates substrate utilization and hunger signals
• Blood glucose fluctuations trigger hunger sensations
  • Hypoglycemia often leads to increased appetite
• Liver acts as an energy sensor, detecting changes in nutrient availability
  • Sends signals to the brain via the vagus nerve
• Integration of multiple physiological signals
  • Hormones (insulin, glucagon)
  • Neural inputs (vagal afferents)
  • Metabolites (glucose, fatty acids, amino acids)

Homeostatic Hunger Regulation

• Hypothalamus plays a central role in processing signals and coordinating hunger response
• Involves complex interplay between central nervous system and peripheral organs
• Disturbances in homeostatic hunger regulation contribute to eating disorders and metabolic diseases
  • Example: Diabetes can disrupt normal hunger and satiety cues due to insulin dysregulation
  • Example: Hypothalamic damage can lead to hyperphagia or anorexia, depending on the affected region

Short-Term vs Long-Term Satiety

Short-Term Satiety Signals

• Arise primarily from the gastrointestinal tract, provide information about the current meal
• Cholecystokinin (CCK) released by small intestine in response to nutrient ingestion
  • Promotes feelings of fullness and reduces meal size
• Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) produced by intestines
  • Slow gastric emptying and promote satiety
• Gastric distension detected by mechanoreceptors in stomach wall
  • Provides rapid satiety signal to the brain
• Primarily influence meal size and duration
• Example: CCK release after fatty meal contributes to earlier meal termination
• Example: Gastric bypass surgery alters gut hormone release, leading to earlier satiety

Long-Term Satiety Signals

• Reflect overall energy balance and adiposity levels in the body
• Leptin serves as primary long-term satiety signal
  • Levels correlate with total body fat stores
• Insulin acts as both a short-term and long-term satiety signal in the brain
  • Promotes satiety and reduces food intake centrally
• Modulate overall energy intake and expenditure over extended periods
• Integration of short-term and long-term satiety signals in the brain determines overall feeding behavior
• Example: Chronically elevated leptin levels in obesity contribute to leptin resistance
• Example: Insulin resistance in type 2 diabetes can disrupt long-term satiety signaling