Leptin and Appetite Regulation Quiz

Starting and Stopping Eating

• Peripheral factors influence starting and stopping eating.
• Digestion's consequences are being focused on.
• Food breakdown products, the body's response to them, and associated blood-borne chemicals are key.
• These have effects on hunger and satiety.
• Short and long-term energy regulation is considered.

Glucostatic Theory 1

• Glucose is the brain's primary energy source and for other cells.
• Blood sugar levels drop before meals and rise after.
• Presumed relationship between blood sugar levels and hunger/satiety.

Glucostatic Theory 2

• Mayer claimed that high arterial blood sugar with low venous blood sugar indicates no hunger.
• Low arterial blood sugar with low venous blood sugar indicates hunger.
• Significant correlations between blood sugar levels and hunger are observed.
• Injecting insulin (reducing blood sugar) triggers hunger.
• Reducing blood sugar by 50% leads to a 200% increase in caloric intake.

OK, but...

• Glucostatic theory works for daily energy needs, but not long-term weight regulation.
• Regulation of body weight is important for maintaining fat stores and responding to short-term food shortages/seasonal changes.

Lipostatic Theory

• Focuses on the need to maintain body weight over long periods, when food availability may fluctuate.
• The body's main energy storage during periods with limited food is fat.
• 1 kilogram of body fat is roughly equivalent to 7800 kcal.
• Humans typically have around 10% body fat, which represents approximately 20 days of energy.
• A set point concept is used to describe the body's weight maintenance mechanism.

Set Point

• The body works to restore a set point if there are changes from this point.
• Variables such as environmental and genetic factors can influence the set point.
• Processes such as pregnancy and puberty impact fat redistribution.
• Homeostasis is the process of maintaining this set point.
• Glucostatic and lipostatic theories are both homeostatic models.

Leptin 1

• Two types of fat cells exist in the body - brown fat and white fat.
• White fat cells store fat and secrete the hormone leptin into the bloodstream, levels of which reflect fat stores.
• The size of the fat cell is related to the amount of leptin it secretes.

Leptin 2

• Increasing leptin levels typically result in reduced hunger and increased feelings of fullness.
• Lower leptin levels stimulate appetite.
• In obese individuals, leptin levels may be high but the body may not respond appropriately (leptin resistance).
• There is evidence of a circadian rhythm to leptin secretion.
• Leptin levels are highest at night and lowest in the day.

Leptin 3

• Leptin deficiency can lead to obesity in mice (ob/ob mice) and humans.
• Injections of leptin can reverse the obesity in some human cases.
• Another type of mouse, db/ob, lacks leptin receptors and is also obese, but leptin injections are ineffective.

Leptin 4

• Circadian rhythm (daily cycle) influences leptin secretion.
• Leptin levels may be linked to eating patterns, especially in the case of Night Eating Syndrome. (circadian variation of leptin secretion might affect meal timing).

How Do These Theories Fair?

• Lipostatic theory is generally well-supported.
• Glucostatic theory has faced some issues.
• Blood sugar ratio and hunger may not always correlate well.
• Alternate indicators for set-point in blood sugar are explored.
• Insulin is considered as a potential factor that can influence blood sugar and appetite.
• Glucostatic theory might be only relevant at extreme conditions.

Insulin 1

• Insulin is a hormone regulating glucose metabolism.
• Insulin forces the liver and muscle cells to store glucose as glycogen.
• Promotes uptake of fats into fat cells.
• Blood sugar regulation is closely linked to insulin.
• Any abnormalities can be serious.

Insulin 2

• Type I diabetes is caused by a lack of insulin.
• Complications include neuropathy, ulcers, blindness, renal failure, and heart disease.
• Type II diabetes is also problematic and linked to body mass.
• Insulin resistance in the cells is involved.

Insulin 3

• Insulin affects appetite in complex ways.
• Artificially raising insulin levels before a meal can trigger hunger.
• A preparatory process, in response to food cues, may increase insulin signaling, leading to anticipatory hunger (and potentially over-eating).
• Artificially raising insulin levels during a meal can reduce food intake.
• This apparent contradiction illustrates the complexity of the system.

Cellular Glucose Metabolism

• Glucose metabolism in hypothalamus cells may be a marker indicating short-term energy needs.
• Several physiological and psychological processes contribute to eating, satiety and the signal that indicates satiety.

Satiating Agents—CCK

• Cholecystokinin (CCK) is a signal released by the gut.
• Stimulates the gallbladder contraction.
• May slow stomach emptying, influencing satiety.
• Higher protein and fat levels increase CCK release.
• CCK levels in lab rats reduce food intake.
• Demonstrates a role in satiety.
• Criteria for establishing an appetite-regulating chemical include release during feeding, effects from administration, congruent endogenous/exogenous dose, speed of clearing, and absence of other possible causes.

Satiating Agents—Glucagon

• Glucagon is a peptide released by the pancreas, opposing the effects of insulin, raising blood glucose.
• It stimulates glycogen breakdown in the liver, releasing glucose, and converts proteins into glucose.
• Injecting extra glucagon in humans or animals reduces food intake.

Food as a Satiating Agent

• Caloric density (energy content per unit of food), nutrient type, and texture contribute to feelings of fullness.
• Fatty foods initially reduce intake, but prolonged exposure can lead to enhanced intake through adaptations.
• Low-calorie foods (particularly for those habituated to certain types of food) may lead to increased intake.
• Protein-based foods are more filling than carbohydrate-based foods.

Texture

• Calorie-for-calorie, solid foods are more satiating than liquids.
• This may stem from differing rates of stomach emptying and differing sensory signals perceived from the various textures.
• Crunchy foods relate to slower eating rate and greater satiety.

Low Calorie Food

• Repeated exposure to low-calorie foods results in increased intake as flavors and familiarity signals increase food need.
• Associative learning is involved; a particular flavor triggers memories of low-calorie food, increasing the desire to eat similar foods.

Nutrient Type

• Calorie-for-calorie, protein-based foods are more filling than carbohydrate-based foods.
• The satiating effect might come from interactions in the small intestine.

Central Mechanisms

• Brain's role in hunger/satiety.
• Neurochemicals modulating appetite.
• Interaction between peripheral and central mechanisms.
• Conscious control of appetite.
• General models of appetite control.

The Case of “RD”

• Case study illustrating the importance of central mechanisms in eating regulation.
• He suffered from a craniopharyngioma, a brain tumor.
• The cyst pressed on the hypothalamus impacting appetite control.
• Subsequent removal of the cyst improved appetite regulation.

Craniopharyngioma

• Brain tumor typically occurring around the hypothalamus.
• Can cause severe obesity or emaciation.
• Long-term problems with weight regulation are potential consequences following surgery.

Hypothalamic Lesions

• Hetherington & Ranson (1940): Early research studying the effect of lesions on eating behavior in rats.
• Findings suggested that the hypothalamus plays a crucial role.
• Hyperphagia (excessive eating) and obesity were observed in some cases after hypothalamic lesions.

VMH as a Satiety Center

• Certain cells in the VMH are sensitive to blood sugar levels (insulin, metabolic status).
• Destruction of these cells leads to hyperphagia.
• Destruction of other areas in the VMH has a less impactful influence on eating behavior.

A Hunger Center

• A hunger center, specifically in or around the Lateral Hypothalamus (LH), has been identified.
• Damage to these cells results in reduced food intake or starvation.
• Stimulation results in increased food intake.

Stellar's Theory

• Stellar proposed the "brake" (ventromedial hypothalamic) and "accelerator" (lateral hypothalamic) concepts for controlling appetite.

And Now...

• Accumulated evidence for hypothalamic role in appetite.
• Some limitations and questions for continuing research, such as whether lesion sites affect only the targets or also the axons of the VMH/LH.

Target Behavior

• Cognitive abilities, such as learning and memory relating to eating behaviors may correlate to different brain targets.

Lesion location

• Specific lesions are difficult to achieve.
• There are effects beyond the intended site, including damage to axons, which could affect the result.
• Non-specific lesions often have larger and more unpredictable results than targeted ones.

Other Brain Areas

• Other brain areas beyond the hypothalamus are involved in feeding behavior management.
• Areas like the amygdala, insula cortex, orbitofrontal cortex, anterior cingulate cortex, and hippocampus are discussed.

Neuropsychology

• Cases of damage to different brain regions can reveal their role in eating behavior, such as in amnesia cases.
• Amnesia symptoms do not affect hunger and fullness perception.
• Amnesia can be involved with an individual’s inability to recall or process information including memories, events or facts.

Eating & Memory I and II

• HM, a patient with amnesia, could eat repeatedly on two subsequent occasions without recognizing he’d eaten before.
• This implies that memory plays a significant role in eating behavior regulation.
• Cognitive control of eating is likely more important than biological.

Eating and Memory III and IV

• Amnesiac people repeatedly eat despite the memory of having eaten and the biological satiety signals.
• The biological signal on satiety is not fully considered by conscious decision-making.
• Memory associated with past episodes might regulate how much someone is likely to eat in the future.

Eating and Memory V

• Limitations on the research to fully understand hippocampus function.
• The role of the hippocampus can not be fully understood, even if evidence of its likely involvement exists (which it does).
• Several factors influence food intake (social, sensory, biological, cognitive).

Neurochemicals

• Research focuses on neurochemicals that modulate appetite.
• Neurochemicals such as serotonin, dopamine, and neuropeptides (including neuropeptide Y (NPY), corticotrophin-releasing hormone (CRH) and apelin) are considered as crucial for controlling appetite.

Neurotransmitters

• Serotonin and dopamine levels affect meal size and frequency when administered in the brain’s lateral hypothalamus and ventromedial hypothalamus.
• The drugs that are used in psychiatry affect serotonin and dopamine.
• Alterations to these neurochemicals—with associated impacts on appetite and weight management—are prevalent in disorders like anorexia and obesity.

Neuromodulators I and II

• Neuropeptide Y (NPY) increases appetite and is stimulated by food intake.
• Corticotrophin-releasing factor (CRF) alters the set point of body weight and is regulated by leptin.
• Abnormal levels of CRH can impact appetite regulation.

Neuromodulators III

• Apolipoprotein A-IV (apo-A-IV).
• Its presence in the blood might reflect nutrient density, and it might be manufactured centrally in the brain.

Interaction of periphery & CNS

• Review of peripheral and central mechanisms.
• Focus on how peripheral signals and central processes interact regarding signals regarding food intake.
• Examples such as neurotransmitters and neuromodulators.
• Factors such as fat and the paraventricular hypothalamus are also considered.

Who is in Control of What I Eat?

• Environmental, biological, and conscious control factors influence food intake.
• These factors interact in complex ways.
• A boundary model is proposed where biological parameters provide the boundaries.

Extending the Boundary Model

• Both short term and long term factors influence the boundary of food intake.