Lecture 7: Hormones and Feeding Behaviour Flashcards
What is motivation?
- The behavior in pursuit of a goal is a fundamental element of our interaction with the world and with each other.
- Need to send commands to frontal lobe to execute the behaviour.
- You can have external motivation or internal motivation. These can be abstract (learn to play guitare) or simple (drink water)
- All living organsisms share a motivation to obtain basic needs –> Food, water, sex, and social interaction. Hence all must share some function to exucute these basic needs.
How do we regulate motivated behaviors?
- Internal state to control the motivation of these behaviours
- Regulation of motivated behaviors is achieved by the coordinated action of molecules, peptides, hormones, neurotransmitters, acting within specific circuits that integrate multiple signals for complex decisions to be made.
Why do we eat?
- To meet the needs of the structural part of the body (bones and muscles). Need to have all the nutrients for our body to function properly.
- To obtain energy to fuel the body.
- when we are sitting doing nothing, we still need energy to maintain our body temp at 37.
- If we need more energy we have processes that will motivate us to eat more food.
Energy Balance
We eat food to maintain the level of energy that our body needs to function. Food intake –> Homeostases
* The mammalian brain depends on glucose as its main source of energy. –> In the adult brain, neurons have the highest energy demand, requiring continuous delivery of glucose from blood. The brain only uses glucose.
* The brain accounts for ~2% of the body weight, but it consumes ~20% of glucose derived energy making it the main consumer of glucose.
Regulation of food intake
We have two systems that control food intake:
1) Related to the control of energy for the cells.
2) Related to pleasure
Homeostatic system: controls the energy balance. Our body motivated our to go get food.
Hedonic system: associated with the pleasure. The motivation to get food for the pleasure. When we are stressed, we tend to change our food consumption - this is related to the hedonic system.
These two systems are correlated. These usually work in the same brain regions. We have several molecules and hormones that can identify the levels of nutrients that we are lacking.
If you have food available, we don’t need to store energy. So, we can consume the amount of energy that we need to spend and then we can consume more food when we need more energy. This is why we have the hedonic system too. We can select the type and amount of food that we want. We have mechanisms to control that
Environmental factors
There are some environmental factors that influence the hedonic regulation of food intake. Environment influences our eating behaviours.
Ie: if you go to see a movie, you want popcorn.
lunch time - routine makes you hungry.
pass by your favorite food place.
What are the energy balance systems?
The homeostatic pathways control the energy balance by increasing the motivation to it following an imbalance between intake and energy balance. When we consume a lot of energy are energy intake is low so our homeostatic system will motivate us to have food to control this balance.
Animals have homeostatic mechanisms that ensure energy balance:
* Short-term energy balance: act primarily as determinants of satiety to limit the size of individual meals. ie: increase of insulin in our body after we eat
* Long-term energy balance: to keep body mass within a relatively fixed range over weeks, months, or even years. Works according to our body mass. ie, Leptin is a hormone produced by the adiposis tissue that we have in our body. So it can act as a short term regulator or a long term regulator.
Is energy balance a homeostatic process?
Food intake is divorced from homeostatic processes and relies on nonhomeostatic processes such as experience, habits, and availability.
* Give food to the rats always in the same day and after sometimes that the animal will learn the time of the meal. They measure the levels of the molecules in the plasma and they observe that after some time when the animals had the food at a specific time, they started to anticipate the food. Big increase of Ghrelin hormone close to the time of the meal. We also have increase in insulin levels close to the meal but because the glucose is the energy and we are usually motivated to eat when you have lower levels of energy, you have lower levels of insulin in this time point.
Fasting and Refeeding
As animals fluctuate between a well-fed and a fasting state, correlated changes occur in the secretion of hormones, neurotransmitters, and neuromodulators.
Energy balance after consuming a meal
After consuming a meal: Prandial state
* Blood is filled with nutrients. In your blood, you have glucose, fatty acids and ketones. You will use the amount of energy that you need and store what you don’t need to use in that time.
* The brain only uses glucose so glucose is going for neurons and the other cells there is glucose,fatty acids and ketones.
* Energy is stored in two forms: glycogen and triglycerides.
* Glycogen reserves: liver and skeletal muscle.
* Triglyceride reserves: adipose (fat) tissue.
* This process is facilitated by the insulin - called anabolism and occurs after consuming a meal.
Energy Balance: fasting condition
Fasting condition: Postabsorptive state
* In a fasting condition, we use the energy that we have stored before (glycogen going for the liver and muscles and triglycerides going for the adipose tissue).
* Glycogen and triglycerides are broken to be used as fuel. They will be broken down into glucose for the neurons and only after the neurons use all the glucose, then the remaining glucose will go to the other cells. At the same time, the triglycerides from the adipose tissue are going to produce the fatty acids and the ketones for all the cells.
* The system is in proper balance when energy reserves are replenished at the same average rate that they are expended.
* Food is available = anabolism
* fasting = catabolism
What happens if energy exceeds our need or fails our need for energy
- If the intake and storage of energy consistently exceed the usage, the amount of body fat, increases, eventually resulting in obesity.
- If the intake of energy consistently fails to meet the
body’s demands, loss of fat tissue occurs, eventually resulting in starvation. - however, we have a lot of hormones, different backgrounds and diseases that influence salvation and obesity.
Energy balanced in well-fed animas vs fasting animals
- Remember, when we consume the energy that we need, we start to store the energy in the body fat, in the adipose tissue and also in the liver.
- lipogenic enzymes = produce the adipose tissue, lipolytic enzymes = break the fat tissue
Energic Balance: orexigenic vs anorexigenic?
- An orexigenic, or appetite stimulant, is a hormone or compound that increases appetite and may inducehyperphagia. Increase of food intake.
- ie: NPY, AgRP, MCH, Orexin A,
- An anorexigenic is a hormone, or compound that reduces appetite,resulting in lower food consumption. Decrease of food intake. ie: Alpha MSH, CRH, TRH, Serotonin
METABOLISM DURING THE WELL-FED STATE
After a meal, there are two phases of energy utilization and storage:
1. The postprandial phase –> The postprandial state, or the fed state, occurs after meal ingestion and embodies the digestion and absorption of nutrients (6–12 h). Absorption of nutrients. Occurs immediately after a meal.
2. The postabsorptive phase –> Postabsorptive state is the period when the nutrients are digested, absorbed, utilized and stored in the designated tissues. Start to put the nutrients in the adipositive tissue and liver. Insulin secretion rises while glucagon secretion falls
The postprandial phase and the postabsorptive phase?
METABOLISM DURING THE WELL-FED STATE
1. The postprandial phase:
Occurs immediately after the ingestion of food.
2. The postabsorptive phase:
Insulin secretion rises while glucagon secretion falls.
METABOLISM DURING THE WELL-FED STATE: Insulin, what it does?
Other hormones that also facilitate this condition and process in well-def animals: epinephrine, norepinephrine, glucocorticoids, thyroid hormones, growth hormone, somatomedin, and glucagon.
In a well-fed state, insulin:
- Helps the Liver in conversion of glucose to glycogen.
- then the glycogen is stored in the liver and in muscle.
- Insulin facilitates the transport of glucose into muscle and fat cells and transport of amino acids into muscle cells.
- In the liver: amino acids are converted into ketone bodies.
- In peripheral cells: insulin is necessary for glucose oxidation and lipogenesis, processes that result in the storage of fat in adipose tissue.
METABOLISM DURING THE WELL-FED STATE: What are the 2 phases of insulin release?
There are two phases of insulin release in animals:
1) The cephalic phase:
* Release of insulin from the pancreatic cells (even before we start eating the food) occurs as a result of the sensory stimuli associated with food intake (before any new nutrients) –> this can be felt as salivation or feeling more hungry.
2) The gastrointestinal phase (already eaten and we are in the absorption phase).
* Our body needs insulin to start all the processes that occur when we are in a well-fed state (from previous Q-card).
* The primary storage of excess nutrients taken in during a meal occurs in the GI phase, when insulin is released in response to the absorption of nutrients from the gut.
METABOLISM DURING THE FASTING STATE
- The energy we have in our body is already consumed so we need to use our stores to provide energy.
- Energy reserves are mobilized from storage to meet your energy needs.
- Metabolic system is designed to provide sufficient levels of energy to the brain.
- After fasting, ketones are formed, and these can also be used by the brain when glucose is scarce.
- Glucagon release, gluconeogenesis, and sympathetic stimulation of fat breakdown are the most common mechanisms for raising blood sugar levels without eating.
- During the fasting state, cells in the periphery switch from metabolizing glucose for ATP production to metabolizing free fatty acids mobilized from the lipids stored in adipose tissue for the energy needs of the body.
METABOLISM DURING THE FASTING STATE: what is the metabolic system for?
Metabolic system is designed to provide sufficient levels of energy to the brain.
Remember the different levels of nutrients we have in animals in well-fed state vs fasting states.
- in well-fed animals we have anabolic processes to produce energy to be stored.
What are the 3 processes activated during the fasting state?
- GLYCOGENOLYSIS
The breakdown of stored glycogen in the liver or muscles to provide a steady supply of glucose for energy. - LIPOLYSIS
The breakdown of adipose tissue into free fatty acids. - GLUCONEOGENESIS
The production of glucose from amino acids, a process that occurs in the liver in response to mild fasting.
DERANGED ENERGY METABOLISM
Diabetes: characterized by high levels of blood glucose (blood sugar). Too much sugar in the blood can cause serious health problems.
- beta cells produce insulin. insulin binds to its receptors on target cells and induce glucose intake.
Type 1 diabetes: insulin-dependent
- beta cells of the pancreas are destroyed by immune cells by mistake.
- genetic factors play a role
- less insulin is produced, less insulin binds to receptors, less glucose is taken into the cell and more glucose stays in the blood.
- Early onset
- symptoms starts suddenly
- managed with insulin injections
Type 2 diabetes: insulin-resistance
- the pancreas produces enough insulin but something either goes wrong with the receptor binding or insulin signalling inside the target cells.
- The target cells are not receptive to insulin so they dont import glucose and glucose stays in the blood.
- Here, genetic factors predispose succeptibility to the disease but it seems that lifestyle plays a very important role in Type II: obesity, inactive lifestyle, unhealthy diet.
- Adult onset
- symptoms appear gradually and start after the age of 30.
- Type 2 diabets account for 80-90% of all diabetics.
- Management focuses on weight loss and includes a low carb diet.
Gestational diabetes:
- occurs in pregnant women
- usually resolves after the birth of the baby
Prediabetes:
- blood sugar levels is at the borderline, higher than normal but lower than diabetics.
- It may or may not progress to diabetes.
We do not need insulin for glucose in the brain.
CONTROL OF FOOD INTAKE
- Homeostatic needs
- Hedonic intake
- Executive function: decision making and impulse control
CONTROL OF FOOD INTAKE
- Obesity is not only the result of overeating. People begin to become obese and then they have an increase in the drive to eat. So it is actually that they begin to become obese and then they begin to eat more.
- Studies have observed more than 32 candidate obesity genes, most of which are expressed in or act on the brain.
- There is a sensory system that monitors metabolic fuel oxidation and changes food intake, energy expenditure, and body fat storage and breakdown to maintain a constant supply of metabolic fuels for intracellular oxidation.
Leptin
- Produced by the adipose cells and tissue (also called adiponectin;
- Leptin circulates in concentrations that are
proportional to the total amount of fat in the body. - When we have leptin circulating in higher levels in our body, it is because we have lots of nutrients stored in the adipose tissue. THe leptin indicates to the brain the level of nutrients we have in our body.
- When stored fat is being used for energy, the blood levels of leptin fall faster than the levels of fat being metabolized (indicates to the brain that we need more food). –> This reduction in circulating leptin suggests that this hormone is a “starvation” signal
- Leptin levels are higher when you have higher storage of energy in the adipose tissue. So, leptin indicates to the brain that we don’t need to have food and you decrease the levels of food intake.
What does leptin do?
- Connection between body fat and feeding behavior: communication from adipose tissue to the brain. Results in the increase or decrease in the feeding behaviour.
- Leptin is the protein encoded by the ob gene.
The hormone leptin, released by adipocytes (fat cells), regulates body mass by acting directly on neurons of the hypothalamus that decrease appetite and increase energy expenditure.
- Regulation of energy homeostasis, neuroendocrine function, and metabolism.
- Other effects of leptin involving regulation of immune function.
- leptin is produced according to the levels of fat tissue that we have (adipose tissue),
- higher leptin levels decreases appetite and increases energy expenditure and the opposite is true.
Insulin
Another peripheral signal that is associated with food intake is the insulin.
* We know that there is an association between the insulin release and the meal termination.
* The hunger ensues when the insulin levels drop at the end of the postabsoptive phase.
Ghrelin
- We have several hormones released from the gut that are associated with the control of food and behaviour.
- Several of them are associated with a decrease in food intake.
- Two important ones: GLP-1 and Ghrelin
- Ghrelin is the only one associated with the INCREASE of eating behavior.
Studies with injections of Ghrelin
- These studies have indicated that Ghrelin stimulates food intake and increases the body mass in animals. Also observed in humans.
- Systemic injections of ghrelin stimulated food intake and increased body mass in rats.
- Blood concentrations of ghrelin peaked around the time of meal onset to stimulate eating behaviour.
Where are ghrelin neurons found in the brain?
- Ghrelin expression: neurons adjacent to the third ventricle. These neurons send axons onto hypothalamic circuits.
- Ghrelin is produced in the gut but they have some receptors in regions of the hypothalamus and they act as to stimulate other neurons there (ie: NPY)
- Ghrelin stimulated activity of NPY neurons in the arcuate nuclei.
- Mimicked the effects of NPY in the PVN.
Hypothalamus and feeding
- Some studies suggest that there are specific nuclei of the hypothalamus associated with eating, obesity and starvation.
- We know that all these regions are important to control the food intake.
Ghrelin in terms of leptin
- Ghrelin seems to work in opposition to leptin: opposite effects on hypothalamic neurons that produce the anorectic neuromodulator and orexigenic peptides.
- The circulating concentrations of ghrelin and leptin are inversely correlated.
What lesions will influence feeding?
Bilateral lesions of the lateral hypothalamus were shown to interfere with all motivated behaviors, not just feeding.
- not just influences feeding behaviour but influences all motivated behaviors.
What is the hypothalamus associated with?
Homeostatic regulation of energy, food intake, thirst, temperature, sexual dimorphism, sleep and circadian rhythm.
The role of the hypothalamus
- Arcuate nuclei of the hypothalamus contain two opposing sets of neuronal circuitry:
(1) a feeding stimulatory circuit
(2) a feeding inhibitory circuit
Both circuits send signals primarily to the PVN and to other nuclei of the hypothalamus: modulate feeding behavior. –> The feeding stimulatory and feeding inhibitory circuits: modulated by peripheral hormonal signals that cross the blood-brain barrier, such as leptin, insulin, ghrelin.
Feeding stimulatory circuit
Note: In fasting state: we are breaking stored energy from the liver only.
Underfed state:
If you are stimulating the feeding stimulatory circuit, you are getting a decrease in Leptin & Insulin
* Molecules in the hypothalamus that are important for stimulating this feeding behaviour circuit are the Neuropeptide Y and the AgRP. They are both located in the hypothalamus. When they identify that we have lower levels of leptin and insulin. they stimulate the feeding behaviour.
Feeding inhibitory circuit
Fed state:
Increase Leptin & Insulin
* Don’t need food = higher levels of leptin and insulin leading to the activation of CART and POMC.Both of these are associated with a decrease of food intake.
Summary of pathways
Well-fed hypothalamus pathway
Reduced food intake pathway
Remember: insulin and leptin are working on both the stimulating and inhibiting feeding behaviour pathways.
Ghrelin vs Insulin/Leptin
Ghrelin generally causes the opposite effect as compared with insulin and leptin.
How does Neuropeptide Y work?
- NPY interacts with receptors in the PVN to cause hyperphagia (increase food behavior).
- LHA: NPY neurons terminate on neurons that secrete other peptides critical for body mass regulation: orexin and melanin-concentrating hormone (MCH).
Agouti-related protein
- AgRP is a stimulator of eating.
- Very small amounts infused into the ventricles of the brain stimulate food intake for up to 6 days.
- Low circulating levels of leptin and insulin activate the NPY/AgRP neurons in the arcuate nuclei.
How does leptin or insulin influence levels of melanocortins?
- Leptin and insulin increase POMC gene expression in the arcuate nuclei to produce more melanocortin.
- Stimulation of POMC-producing neurons to secrete α-MSH, which stimulates MC4 receptors (MC4 receptor is associated with an increase in eating behaviors).
- POMC activation increases conversion of white adipose tissue to brown adipose tissue, which is involved in thermogenesis: increasing brown fat compared with white adipose tissue increases energy expenditure
Main takeaway about leptin and insulin
- Leptin and insulin stimulate a catabolic pathway (POMC/CART neurons) and repress an anabolic pathway (NPY/AgRP neurons), both of which begin in the arcuate nuclei (ARC) and project to the PVN and LHA. Both located in hippothalamus.
- Neuroanatomical model showing the various pathways through which elevated adiposity signals, leptin and insulin, communicate with central autonomic circuits mediating food intake.
Summary table of molecules important for increase or decrease of eating behavior.
CHOLECYSTOKININ
- Primary hormonal factor that provokes satiety.
- CCK is a gastrointestinal peptide hormone that is released during feeding to aid with digestion
- related to decrease in eating behaviour.
GONADAL STEROID HORMONES
Gonadal steroid hormones also influence feeding behavior and subsequent body mass.Males and females have different feeding behaviors, this can be associated with not only behaviors and reward but also with hormones.
* Estrogens have catabolic effects: increasing energy expenditure, thermogenesis, lipolysis, body fat loss).
* Androgens have anabolic effects.
Hedonic regulation of food intake: THE ROLE OF DOPAMINE IN MOTIVATION
- Dopamine is associated with reward and food is associated with reward, hence their relationship. Dopamine regulates motivational behavior, including feeding behaviors.
- The dopamine reward system is recognized as the most prominent system that controls appetite and motivational and emotional drives for food.
STRESS AND EATING BEHAVIOR
Under controlled lab circumstances, acute physical or emotional distress induces increased intake of ‘comfort’ foods in humans and animals, even when they are not hungry and have no homeostatic need for calories.
- Stress is very associated with eating behavior.
- we have 2 effects of stress in the eating behavior, we have acute stress (for some days) = increase intake of comfort food. Chronic stress (long term) = oposite = decrease in food intake.
- Comfort food is more associated with acute stress.
Stress-induced obesity and the emotional nervous
- observed that all students had more intake of comfort food during exams (sweets).
- even when the increase of the food intake was not observed, they observed this change in the type of food that the person eats.
Early development is the foundation of healthy life course.
- some association between the early life stress and some eating behaviors.
- some individuals are more reactive to stressful situations (even in early life). Higher reativity to stress can lead to several alterations in behaviors.
- Animals that are more reactive to stress have alterations in the homeostatis mechanism & hedonic mechanims which are impacting eating behaviors.
- also cognition and mental disorders can affect eating behavior.
Mind over milkshake study
- Mindsets, not just nutrients, determine ghrelin response. Remember ghrelin is released close to the meal time.
- They received a healthy milkshake or an unheathly one (they knew this) - were told they were receiving one of these but they were actually all the same. They then measured the levels of ghrelin before and after consuming the milkshake.
- Although, they are receiving the same milkshakes, the people that got the healthy milkshake did not have a big change in ghrelin level but the ones that received the unhealthy one had an increase in the ghrelin levels. Several psychological mechanisms influencing food intake.
- The effect of food consumption on ghrelin may be psychologically mediated, and mindset meaningfully affects physiological responses to food.
