23-26. Obesity, Diabetes and Nutrition Flashcards
Define
Critical race theory
a theoretical framework in the social sciences that examines society and culture as they relate to categorizations of race, law, and power
Define
Ecological Systems Theory
offers a framework through which community psychologists examine individuals’ relationships within communities and the wider society
Define
FTO gene
an important locus harboring common variants with an unequivocal impact on obesity predisposition and fat mass at the population level
Define
Genome wide association study (GWAS)
an approach used in genetics research to associate specific genetic variations with particular diseases. The method involves scanning the genomes from many different people and looking for genetic markers that can be used to predict the presence of a disease
Define
Ghrelin
a hormone that is produced and released mainly by the stomach with small amounts also released by the small intestine, pancreas and brain. It is termed the ‘hunger hormone’ because it stimulates appetite, increases food intake and promotes fat storage.
Define
Health equity
the notion that everyone should have a fair opportunity to attain their full health potential and that no one should be disadvantaged from achieving this potential if it can be avoided
Define
Hyperphagia
an abnormally great desire for food; excessive eating
Define
Hypogonadism
diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones
Define
Hypotonia
decreased muscle tone
Define
Leptin
a hormone produced by the fat cells in your body. Its main role is to regulate fat storage and how many calories you eat and burn
Define
Malnutrition
a condition that results from eating a diet in which one or more nutrients are either not enough or are too much such that the diet causes health problems
Define
Prader-Willi Syndrome
a complex genetic condition that affects many parts of the body. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development
Define
Uniparental disomy
the situation in which 2 copies of a chromosome come from the same parent, instead of 1 copy coming from the mother, and 1 copy coming from the father
Definition
a theoretical framework in the social sciences that examines society and culture as they relate to categorizations of race, law, and power
Critical race theory
Definition
offers a framework through which community psychologists examine individuals’ relationships within communities and the wider society
Ecological Systems Theory
Definition
an important locus harboring common variants with an unequivocal impact on obesity predisposition and fat mass at the population level
FTO gene
Definition
an approach used in genetics research to associate specific genetic variations with particular diseases. The method involves scanning the genomes from many different people and looking for genetic markers that can be used to predict the presence of a disease
Genome wide association study (GWAS)
Definition
a hormone that is produced and released mainly by the stomach with small amounts also released by the small intestine, pancreas and brain. It is termed the ‘hunger hormone’ because it stimulates appetite, increases food intake and promotes fat storage.
Ghrelin
Definition
the notion that everyone should have a fair opportunity to attain their full health potential and that no one should be disadvantaged from achieving this potential if it can be avoided
Health equity
Definition
an abnormally great desire for food; excessive eating
Hyperphagia
Definition
diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones
Hypogonadism
Definition
decreased muscle tone
Hypotonia
Definition
a hormone produced by the fat cells in your body. Its main role is to regulate fat storage and how many calories you eat and burn
Leptin
Definition
a condition that results from eating a diet in which one or more nutrients are either not enough or are too much such that the diet causes health problems
Malnutrition
Definition
a complex genetic condition that affects many parts of the body. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development
Prader-Willi Syndrome
Definition
the situation in which 2 copies of a chromosome come from the same parent, instead of 1 copy coming from the mother, and 1 copy coming from the father
Uniparental disomy
How does obesity occur?
Arises from energy imbalance, when energy intake is more than energy expended through physical activity
How is the weight status of adults typically measured?
Usually calculated in population surveys by measuring a person’s body mass index (BMI=weight in kg/ height2), or waist circumference
How is the weight status percentiles of children broken up?
Underweight: BMI less than 5th percentile
Healthy weight: BMI between 5th and 85th percentile
Overweight: BMI between 85‐95th percentile relative to age and sex
Obesity: BMI 95th percentile and above relating to age and sex
Why does childhood obesity/overweight matter?
- Childhood obesity continues to be one of the most challenging public health issues of this century (WHO, 2016).
- Associated with serious adverse short‐ and long‐term outcomes
- Obesity‐related behaviours are established in early childhood and track through to adulthood (Han, Lawlor, & Kimm, 2010).
- First 2000 days (conception to 5 years) are viewed as a crucial period for child obesity prevention.
A recent meta analysis showed children with obesity have a ______ increased risk of having obesity in adulthood
A recent meta‐analysis showed children with obesity have a fivefold increased risk of having obesity in adulthood
What are the adverse health outcomes of children with obesity?
“Lifestyle” health conditions such as hypertension and metabolic disorders (WHO, 2016)
Children with obesity are more likely to be admitted to hospital and have a 60% higher health care costs compared to children with healthy weight status (Hayes et al., 2016)
What are the implications of childhood obesity beyond physical health?
Negatively impacts self‐esteem and mental health
Long‐term education
Quality of life
Over the past decades, obesity researchers have used _______________ to summarise the complex interplay between these multidimensional contributors to excess child weight development and inform childhood obesity research and prevention strategies
Over the past decades, obesity researchers have used Ecological Systems Theory to summarise the complex interplay between these multidimensional contributors to excess child weight development and inform childhood obesity research and prevention strategies
What places parent and child factors as the most proximal influences on the development of overweight and obesity during early childhood?
Ecological systems theory
Why do high quality parent-child interactions matter to child development of obesity?
- Responsive, sensitive parenting helps to build trust in the relationship and the child learns that they can rely on their caregiver to comfort them during times of distress and support their exploration of the world
- High quality interactions impact on development of the child’s neurophysiological structures (associated with stress response, sleep, appetite) involved in supporting optimal development of self‐regulation
- Stress response, sleep and appetite are implicated in energy regulation and eating behaviour
What are the child-level factors that may play a role in feeding interactions?
Age
Gender
Temperament
Self-regulation
Eating behaviour
True or False:
Excess weight is considered to be a leading cause of preventable death
True
What factors contribute to obesity?
Genetics/epigenetics
Lifestyle eating/exercise patterns
Socioeconomic status
Psychological factors
Cultural background
Age
Hormonal, metabolic and physiological factors
Sleep disturbances
True or False:
Most genetically caused obesity is monogenic
False
Monogenic forms of obesity are relatively rare
What is the heritability of BMI?
50-90%
What is the most common syndromic cause of obesity?
Prader-Willi Syndrome
What are the symptoms of Prader-Willi Syndrome?
- Hypotonia: weak muscle tone, and floppiness at birth.
- Hypogonadism: immature development of sexual organs and other sexual characteristics.
- Obesity: caused by excessive appetite and overeating (hyperphagia), and a decreased calorific requirement owing to low energy expenditure levels, although obesity is not normally a feature of those whose food intake is strictly controlled.
- Central nervous system and endocrine gland dysfunction: causing varying degrees of learning disability, short stature, hyperphagia, somnolence (excessive sleepiness), and poor emotional and social development.
What is the genetic cause of Prader-Willi?
Different mechanisms can lead to lack of expression of the paternal chromosome 15q11- q13 genes, hence causing PWS:
- 65-75% cases: De novo microdeletion of this region on the paternal chromosome
- 20-30% cases: Maternal uniparental disomy (UPD)
- Two maternal chromosomes, none from father
- Associated with advanced maternal age
- 2-5% or fewer cases: Imprinting error epigenetic transference.
Levels of which hormone are increased in children with Prader Willi Syndrome?
Ghrelin
Which cell type produces leptin?
Fat cells
Double knockout of the ob gene (leptin) caused what symptoms in mice?
Profound obesity
Glucose intolerant/ insulin resistant
Infertile
Cold intolerant
Immune Dysfunction
No circulating leptin levels
What happens if a organism is unable to produce leptin?
Without leptin the body believes it is constantly in a state of starvation or there is an absence of fat stores.
This signals to the brain to increase food intake and reduce energy expenditure.
No satiation- patients eat uncontrollably.
Leads to profound morbid obesity.
How is congenital leptin deficiency in humans treated?
Leptin replacement therapy
True or False:
Individuals with leptin receptor mutations respond well to leptin replacement therapy
False
These individuals already have elevated circulating leptin. The issue isn’t the lack of leptin, its the inability to recognise ti
What is the relationship between circulating leptin and BMI?
As BMI increases, level of circulating leptin also increases indicating leptin resistance
How do we identify susceptibility genes?
Genome-wide association studies (GWAS)
What happens when FTO is over expressed in mice?
Increased body weight
Drastically increased fat mass
Increased food intake
Increased preference for higher calorie foods
Reduced physical active and energy expenditure
Impaired browning of white adipose tissue
Define
Adipokines
cytokines secreted by adipose tissue
Define
Adiponectin
a protein produced and secreted by fat cells that is normally abundant in the blood plasma but has reduced expression in those with obesity and insulin resistance
Define
Agouti-related protein (AgRP)
a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized only in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus. It is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure
Define
Arcuate nucleus (ARC)
located around the third ventricle near the median eminence, is involved in many processes including regulating the release of hormones (eg, GnRH and prolactin) from the anterior pituitary, the LH surge, lactation, appetite and growth hormone release
Define
Ceramide
a family of waxy lipid molecules. They can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells
Define
Cholecystokinin (CCK)
a hormone secreted especially by the duodenal mucosa that regulates the emptying of the gallbladder and secretion of enzymes by the pancreas and that has been found in the brain
Define
Diacylglyceride (DAG)
a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. It is able to suppress the accumulation of body fat
Define
Glucagon-like peptide-1 (GLP-1)
produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. It has the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin
Define
GLUT4
the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle (skeletal and cardiac)
Define
Insulin
a protein pancreatic hormone secreted by the beta cells of the islets of Langerhans that is essential especially for the metabolism of carbohydrates and the regulation of glucose levels in the blood and that when insufficiently produced results in diabetes mellitus
Define
Lateral hypothalamus (LH)
contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system;[2] this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others
Define
M1 macrophage
Classically activated, pro-inflammatory macrophages
Define
M2 macrophage
Alternatively activated, anti-inflammatory macrophages
Define
Median eminence
a raised area in the floor of the third ventricle of the brain produced by the infundibulum of the hypothalamus
Define
Melanocortin 4 (MC4) receptor
a G protein-coupled receptor that binds α-melanocyte stimulating hormone (α-MSH). Involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function
Define
Melanocortins
a group of peptide hormones which include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH), and are derived from proopiomelanocortin (POMC) in the pituitary gland
Define
Metabolic syndrome
a syndrome marked by the presence of usually three or more of a group of factors (such as high blood pressure, abdominal obesity, high triglyceride levels, low HDL levels, and high fasting levels of blood sugar) that are linked to increased risk of cardiovascular disease and type 2 diabetes
Define
Neuropeptide Y (NPY)
a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. In the brain, it is produced in various locations including the hypothalamus, and is thought to have several functions, including: increasing food intake and storage of energy as fat
Define
Orexigen
Any substance that stimulates appetite
Define
Paraventricular nucleus (PVN)
a discrete band of neurons in the anterior part of the hypothalamus that produce vasopressin and especially oxytocin and that innervate the neurohypophysis
Define
Peptide YY (PYY)
a short (36-amino acid) peptide released from cells in the ileum and colon in response to feeding. In the blood, gut, and other elements of periphery, it acts to reduce appetite
Define
Pro-opiomelanocortin (POMC) neurons
Produces a specific type of molecule that acts as a precurosor to appetite supressor molecules
Define
Resistin
an adipose-derived hormone (similar to a cytokine) whose physiologic role has been the subject of much controversy regarding its involvement with obesity and type II diabetes mellitus
Define
Tanycytes
special ependymal cells found in the third ventricle of the brain, and on the floor of the fourth ventricle and have processes extending deep into the hypothalamus. It is possible that their function is to transfer chemical signals from the cerebrospinal fluid to the central nervous system
Define
Type 2 diabetes
a common form of diabetes mellitus that develops especially in adults and most often in obese individuals and that is characterized by hyperglycemia resulting from impaired insulin utilization coupled with the body’s inability to compensate with increased insulin production
Define
Vagal afferent
nerves that innervate the gastrointestinal tract and contain dense axonal projections and complex terminal structures that detect sensory stimuli and transmit signals towards the CNS
Define
Ventromedial hypothalamus (VMH)
a distinct morphological nucleus involved in terminating hunger, fear, thermoregulation, and sexual activity.” This nuclear region is involved with the recognition of the feeling of fullness.
Define
Visfatin
a protein present in several mammals, encoded by the NAMPT gene within humans, expressed to a high degree in visceral fat
Define
α-Melanocyte-stimulating hormone (α-MSH)
an endogenous peptide hormone and neuropeptide of the melanocortin family. It is the most important hormone in its family responsible for pigmentation primarily of the hair and skin. It also plays a role in feeding behavior, energy homeostasis, sexual activity, and protection against ischemia and reperfusion injury
Definition
cytokines secreted by adipose tissue
Adipokines
Definition
a protein produced and secreted by fat cells that is normally abundant in the blood plasma but has reduced expression in those with obesity and insulin resistance
Adiponectin
Definition
a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized only in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus. It is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure
Agouti-related protein (AgRP)
Definition
located around the third ventricle near the median eminence, is involved in many processes including regulating the release of hormones (eg, GnRH and prolactin) from the anterior pituitary, the LH surge, lactation, appetite and growth hormone release
Arcuate nucleus (ARC)
Definition
a family of waxy lipid molecules. They can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells
Ceramide
Definition
a hormone secreted especially by the duodenal mucosa that regulates the emptying of the gallbladder and secretion of enzymes by the pancreas and that has been found in the brain
Cholecystokinin (CCK)
Definition
a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. It is able to suppress the accumulation of body fat
Diacylglyceride (DAG)
Definition
produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. It has the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin
Glucagon-like peptide-1 (GLP-1)
Definition
the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle (skeletal and cardiac)
GLUT4
Definition
a protein pancreatic hormone secreted by the beta cells of the islets of Langerhans that is essential especially for the metabolism of carbohydrates and the regulation of glucose levels in the blood and that when insufficiently produced results in diabetes mellitus
Insulin
Definition
contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system;[2] this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others
Lateral hypothalamus (LH)
Definition
Classically activated, pro-inflammatory macrophages
M1 macrophage
Definition
Alternatively activated, anti-inflammatory macrophages
M2 macrophage
Definition
a raised area in the floor of the third ventricle of the brain produced by the infundibulum of the hypothalamus
Median eminence
Definition
a G protein-coupled receptor that binds α-melanocyte stimulating hormone (α-MSH). Involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function
Melanocortin 4 (MC4) receptor
Definition
a group of peptide hormones which include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH), and are derived from proopiomelanocortin (POMC) in the pituitary gland
Melanocortins
Definition
a syndrome marked by the presence of usually three or more of a group of factors (such as high blood pressure, abdominal obesity, high triglyceride levels, low HDL levels, and high fasting levels of blood sugar) that are linked to increased risk of cardiovascular disease and type 2 diabetes
Metabolic syndrome
Definition
a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. In the brain, it is produced in various locations including the hypothalamus, and is thought to have several functions, including: increasing food intake and storage of energy as fat
Neuropeptide Y (NPY)
Definition
Any substance that stimulates appetite
Orexigen
Definition
a discrete band of neurons in the anterior part of the hypothalamus that produce vasopressin and especially oxytocin and that innervate the neurohypophysis
Paraventricular nucleus (PVN)
Definition
a short (36-amino acid) peptide released from cells in the ileum and colon in response to feeding. In the blood, gut, and other elements of periphery, it acts to reduce appetite
Peptide YY (PYY)
Definition
Produces a specific type of molecule that acts as a precurosor to appetite supressor molecules
Pro-opiomelanocortin (POMC) neurons
Definition
an adipose-derived hormone (similar to a cytokine) whose physiologic role has been the subject of much controversy regarding its involvement with obesity and type II diabetes mellitus
Resistin
Definition
special ependymal cells found in the third ventricle of the brain, and on the floor of the fourth ventricle and have processes extending deep into the hypothalamus. It is possible that their function is to transfer chemical signals from the cerebrospinal fluid to the central nervous system
Tanycytes
Definition
a common form of diabetes mellitus that develops especially in adults and most often in obese individuals and that is characterized by hyperglycemia resulting from impaired insulin utilization coupled with the body’s inability to compensate with increased insulin production
Type 2 diabetes
Definition
nerves that innervate the gastrointestinal tract and contain dense axonal projections and complex terminal structures that detect sensory stimuli and transmit signals towards the CNS
Vagal afferent
Definition
a distinct morphological nucleus involved in terminating hunger, fear, thermoregulation, and sexual activity.” This nuclear region is involved with the recognition of the feeling of fullness.
Ventromedial hypothalamus (VMH)
Definition
a protein present in several mammals, encoded by the NAMPT gene within humans, expressed to a high degree in visceral fat
Visfatin
Definition
an endogenous peptide hormone and neuropeptide of the melanocortin family. It is the most important hormone in its family responsible for pigmentation primarily of the hair and skin. It also plays a role in feeding behavior, energy homeostasis, sexual activity, and protection against ischemia and reperfusion injury
α-Melanocyte-stimulating hormone (α-MSH)
What factors contribute to the development of metabolic syndrome?
Inflammation
Increased TAGs
Decreased HDL
Oxidative stress
Abdominal adiposity
Pro-thrombotic state
Blood glucose
Insulin resistance
Increased hypertension
What diseases are associated with metabolic syndrome?
Neurological disorders
PCOS
Cancer
Cardiovascular disease
Type II diabetes
Stroke
NASH
Which three tissues does insulin directly effect? What does it cause at these locations?
Liver
- Decreased hepatic glucose production via inhibition of gluconeogenesis
Skeletal muscle
- Increased glucose uptake (via GLUT4) - glycogen
- Uptake of amino acids - protein synthesis
Adipose tissue
- Increase glucose uptake (via GLUT4)
- Inhibits lipolysis
- Triglyceride synthesis
Which three tissues does insulin directly effect? What does insulin resistance cause at these locations?
Liver
- Increased hepatic glucose production contributes to hyperglycaemia
Skeletal muscle
- Decreased glucose uptake cotnributes to hyperglycaemia
Adipose tissue
- Increased lipolysis leads to increased circulating FFA
What proportion of people with diabetes don’t know they have it?
1/3
How is T2 diabetes diagnosed?
Fasting blood glucose (normal < 5.5 mmol/L)
Oral glucose tolerance test for people > 5.5. mmol/L (normal < 7.8 mmol/L)
What is the heritability of T2 diabetes?
Having a parent with diabetes increases the risk of diabetes 2-fold, with up to 6-fold risk when both parents are affected
T2 diabetes is characterised by defects in two areas, what are they?
Insulin resistance
β-cell dysfunction
What causes β-cell failure seen in T2 diabetes?
β-cell compensation causing increased secretion of insulin. Exhausts cells
Which tissue is responsible for the greatest uptake of glucose after eating?
Skeletal muscle
In what four ways is diabetes also a disease of defective lipid metabolism?
Lipotoxicity
Inflammation (low-grade)
Altered endocrine signals
Mitochondrial dysfunction
How do long-chain fatty acids block insulin signalling in skeletal muscle?
DAGs and ceramides prevent GLUT4 from reaching the cell membrane, causing decreased glucose uptake
What causes the increase in circulating FFA in diabetes?
Adipocytes undergo apoptosis dues to toxicity from storing too much fat. Releases FFA into bloodstream
What type of macrophage contributes to inflammation in obese individuals?
M1 macrophages
What are the main cytokines contributing to the low-grade inflammation in obese individuals?
IL-6
TNFα
What is an inflammatory hallmark of the obese state?
Recruitment of M1 macrophages
How do M1 macrophages impact insulin signalling?
Proinflammatory cytokines impair insulin signalling. Prevents GLUT4 transportation and glucose uptake in skeletal muscle. Increases hepatic glucose production
What effects do adipokines have on the body?
Energy expenditure
Food intake
Kidney function
Angiogenesis
Insulin sensitivity
Inflammation
Immunity
What are the four major adipokines?
Leptin
Adiponectin
Resistin
Visfatin
Which adipokine opposes resistin?
Adiponectin
What happens to mitochondrial in diabetes?
Reduced number, size and activity
Reduced fatty acid oxidation proteins
Increased reactive oxygen species (ROS) - inhibit insulin signalling
What is the main endogenous appetite stimulator?
Ghrelin
What molecules inhibit appetite?
Leptin
Insulin
GLP-1
CCK
PYY
What is the major site of homeostatic control of food intake?
Arcuate nucleus (ARC)
What three neuropeptides are released in the arcuate nucleus neurons to control feeding?
POMC
- Produced by POMC neurons
- Precursor to melanocortins (i.e. αMSH) which inhibit FI via MC4R
NPY
- Produced by NPY/AgRP neuron
- Most potent orexigen; coexpressed with AgRP; acts on Y1 and Y5
AgRP
- Produced by NPY/AgRP neuron
- Coexpressed with NPY; antagonises αMSH
What happens to αMSH and AgRP in a appetitde-supressing state?
AgRP is supressed
αMSH is released by the POMC neuron and binds to the MC4 receptor of the PVN neuron
Feeding decreased
What happens to αMSH and AgRP in a appetitde-indicing state?
AgRP released by AgRP/NPY neuron
Binds to MC4 receptors and blocks action of αMSH
Feeding increases
In what ways can NPY/AgRP neurons lead to hunger?
Release of:
- NPY: acts on Y1 and Y5 receptors of PVN orexigenic neurons
- AgRP: antagonises αMSH by binding to MC4 receptor
- GABA: acts directly on GABA receptor located on POMC neuron inhibiting action
What rapid signals control food intake?
Increased food intake:
- NPY activating Y1 and Y5 receptors on orexigneic neurons in PVN
- GABA inhibiting POMC neurons
Decreased food intake:
- Glutamate activating satiety neurons in PVN
What slow signals control food intake?
Increased food intake:
- AgRP inhibits MC4 receptor of satiety neurons in PVN
Decreased food intake:
- αMSH activates MC$ receptor of satiety neurons in PVN
Deletion of NPY/AgRP cells leads to what?
Starvation and death
Deletion of POMC cells leads to what?
Weight gain, obesity and glucose intolerance
Why do endocrine hormones have an effect on the neurons of the arcuate nucleus?
The arcuate nucleus has a leaky blood brain barrier
What causes the leaky BBB of the arcuate nucleus?
Tanycyte barrier and fenestrate cappilaries of the median eminence
Which neurons are considered first order and which are second order?
First order: POMC and NPY/ArRP neurons
Second order: PVN neurons
Which arcuate neurons do do insulin and leptin act on? What do they do?
AgRP/NPY:
- Inhibit decreasing food intake
POMC
- Activate increasing food intake
What are the functions of ghrelin?
Increases food intake
Increases adiposity
Increases blood glucose
Increases growth hormone
When is Ghrelin released?
During negative energy balance (fasting)
Which ARC neurons does ghrelin act on? What does it do?
NPY/AgRP only
- Activates increasing food intake
- Also inhibits POMC neurons via GABA release
Which part of the hypothalamus is considered the feeding center and which is the satiety center? Why?
Ventromedial hypothalamus
- Satiety center
- Lesions of VMH cause obesity
Lateral hypothalamus
- Feeding center
- Lesions of LH causes starvation
What happens when you create lesions in the ventromedial hypthalamus and then later create lesions in the lateral hypothalamus?
- Lesions of VMH cause obesity
- Subsequent lesions of the LH reversed obesity and caused starvation
What is the dual center hypotheisis of feeding?
Which other section of the hypthalamus does leptin act? What does it do?
Ventromedial hypothalamus
Alters BDNF reducing food intake
Where do orexin and melanin act to increase food intake?
Lateral hypothalamus
Which molecule(s) inhibit orexin and melanin to reduce food intake?
Melanocortins (e.g. αMSH)
Where does ghrelin act to increase food intake?
NPY/AgRP neurons of ARC
Where does PYY act to decrease food intake?
Brainstem (vagal afferents)
Area postrema
Arcuate nucleus
Where does GLP-1 act to decrease food intake?
Brainstem (vagal afferents)
Area postrema
Arcuate nucleus
Where does CCK act to decrease food intake?
Brainstem (vagal afferents)
How does GLP-1 inhibit food intake?
Vagal afferent connection
Inhibits food intake via GLP1-R
Acts directly on POMC neurons
Indirectly inhibits NPY/AgRP neurons via GABA
How does PYY inhibit food intake?
Inhibits food intake via Y2 receptors on NPY/AgRP neurons
Inhibits release of NPY/AgRP
