Hormonal Regulation of Appetite and Satiety

Hormonal Regulation of Appetite and Satiety

• The hypothalamus is crucial in metabolic homeostasis, controlling energy intake and body weight.
• Neuropeptides and hormones play a vital role in hypothalamic control of these processes.
• Animal models of obesity are relevant to understanding human obesity.

Obesity - A Disease of the Brain?

• Losing weight once gained is challenging due to brain re-programming.
• Increased body fat alters brain function, influencing the perception of weight as normal.
• Long-term obesity leads to a form of brain re-programming where the brain defends the new weight.

Central Control of Energy Intake and Body Weight

• The central nervous system (CNS) regulates energy balance through behaviour, autonomic nervous system (ANS) activity, and neuroendocrine pathways.
• Behaviour includes feeding and physical activity.
• The autonomic nervous system regulates energy expenditure.
• The neuroendocrine system secretes hormones.
• The brain, specifically the hypothalamus, integrates these signals to determine the final output (feeding behaviour).

Part 1: The Hypothalamus

• The hypothalamus, neuropeptides, hormones, and central signals regulate appetite and satiety.

Hypothalamus and Obesity

• Body weight is maintained through a feedback loop to ensure consistent energy stores.
• The lateral hypothalamus acts as a hunger center, while the ventromedial hypothalamus acts as a satiety center.
• Lesions in these areas either produce anorexia or obesity respectively.

Finding Balance

• The body maintains energy balance through various processes.
• It stores energy during surplus and utilizes stores when needed, such as during starvation.
• Promoting food intake when stores are low and discouraging it when stores are full are key to maintaining balance.
• Orexigenic factors stimulate food intake while anorexigenic factors decrease food intake.

Hypothalamic Regulation - Appetite and Satiety

• Feedback regulation processes respond to body nutritional status, modulating food intake and energy expenditure.
• Short-term signals regulate meal initiation, termination, and frequency between meals.
• Long-term processes, including adiposity signals, also regulate body weight and food intake.

Neuropeptides and Obesity

• There's been a significant surge in understanding hypothalamic regulation of food intake and body weight due to discovered regulatory peptide molecules.
• These molecules are either orexigenic (stimulate appetite) or anorexigenic (reduce appetite).

Melanocortins - αMSH

• αMSH, a melanocyte-stimulating hormone, is formed by cleaving proopiomelanocortin (POMC).
• POMC gene expression is linked to fasting and positive energy balance.
• αMSH inhibits food intake.
• Melanocortin receptors (MC3 and MC4) are key in brain function.

Neuropeptide Y (NPY)

• NPY is a highly abundant peptide in the human brain.
• NPY-containing neurons are found in the arcuate nucleus (ARC).
• NPY injection into the hypothalamus increases food intake and reduces energy expenditure, leading to obesity when repeatedly administered.
• NPY receptor antagonists can reduce food intake, potentially reducing obesity.
• Mice lacking NPY receptors are predisposed to increased susceptibility toward obesity.

Agouti-related Protein (AgRP)

• AgRP co-exists with NPY in ARC neurons.
• AgRP and Agouti are antagonists to MC3 and MC4 receptors.
• AgRP injections lead to long-lasting hyperphagia (increased food intake).

Adiposity Signals - Leptin

• Leptin is a cytokine released from adipocytes.
• Leptin levels correlate with fat mass.
• Leptin has a specific transport system to enter the brain.
• High levels of leptin receptors are found in the ARC of the hypothalamus.
• Intravenous (IVC) injections of leptin decrease food intake and reduce body weight in rodents.
• Neuron-specific deletion of the leptin receptor leads to obesity.

Biological Roles of Leptin

• Leptin influences food intake and energy expenditure, also impacting fat deposition.
• Leptin affects peripheral glucose homeostasis and insulin sensitivity; maintaining the immune and reproductive systems; and angiogenesis, tumorigenesis, and bone formation.

Adiposity Signals - Insulin

• Insulin circulates in proportion to adiposity but is secreted from the pancreas.
• Specialized transport systems carry insulin into the brain.
• High levels of insulin receptors are found in the hypothalamus, particularly in the ARC.
• Intravenous (IVC) insulin reduces food intake and body weight.

Leptin Therapy in DIO

• Most human diet-induced obesity (DIO) cases are characterized by high leptin levels.
• Leptin treatment in DIO is often limited by leptin resistance, which is often present in obese individuals.
• Two main theories explain this resistance: defective leptin transport into the brain or altered signal transduction following leptin binding to its receptor.

Leptin Resistance and Obesity

• Leptin receptor (Ob-Rb) activates multiple signaling cascades.
• These pathways enable leptin to regulate food intake, energy expenditure, peripheral glucose homeostasis, insulin sensitivity, and immune/reproductive function.

Leptin Resistance and DIO

• DIO rodent models are used as indicators for human obesity because of their similarity to human obesity.
• DIO individuals often exhibit hypothalamic and resistance to leptin and insulin, characterized by increased hepatic glucose output and peripheral insulin resistance.
• This frequently results in resistance to peripheral recombinant leptin treatments.
• High circulating leptin and leptin resistance are often observed in individuals with diet-induced obesity (DIO).

Contributors to Hypothalamic Leptin Resistance

• High calorie intake can elevate leptin levels, but this often leads to leptin resistance and a need to restore leptin sensitivity.
• Endoplasmic reticulum (ER) stress in the hypothalamus can reduce leptin sensitivity.
• Chronic low-grade neuroinflammation caused by high calorie intake contributes to leptin resistance.

Summary - Obesity and the Brain

• The hypothalamus is crucial in regulating body weight and food intake.
• Feedback loops modulate food intake and energy expenditure.
• Adiposity signals originate from adipose tissue and pancreas.
• Satiety signals emanate from the gastrointestinal (GI) tract to regulate food intake.
• The brain can become insensitive to leptin and insulin in obesity cases.
• Rodent models of obesity provide insight into the underlying causes of obesity.

Explore the intricate relationship between hormones, the hypothalamus, and appetite regulation. This quiz delves into how neuropeptides affect energy intake and body weight, and how brain function alters with obesity. Understand the central control mechanisms that govern our energy balance and perception of weight.