177. Appetite Regulation Flashcards
__ levels have been shown to increase with weight loss, causing difficulty of maintaining weight loss
Also, amylin, CCK, and PYY levels have been shown to decrease with weight loss, thus satiety is more difficult to achieve
Ghrelin
- Inhibiting neurons that coexpress the orexigenic hormones NPY and AgRP
- Stimulating neurons that coexpress the anorexigenic hormones alpha-MSH and CART
Leptin action in the arcuate nucleus
Fasting plasma levels of __ are high in partients with anorexia nervosa and in subjects w/ diet-induced weight loss
Ghrelin
Lesions to the __ hypothalamus induce excessive hunger
This area acts through MC4 receptor
Ventromedial
What are times when fat stores need to be developed, thus when energy intake»_space; energy expenditure?
Growth and development
Pregnancy
Recovery from an illness
Peptide that is synthesized and released from endocrine L cells from the distal gut in response to food consumption
- particularly dietary fat
Levels increase w/in 30 minutes of nutrients reaching the distal gut
PYY
One of the most potent orexigenic peptides peptides known
Hypothalamic __ mRNA levels are increased under conditions of acute food deprivation and chronic food restriction
NPY
Neuropeptide that is abundantly present in the CNS
Provides a dominant inhibitory tone onto POMC
NPY
Alpha-MSH’s receptor
When stimulated results in down-stream appetite control and energy balance
MC4R
Hypothalamus responds with inflammation when pt is eating on a __
Inflammation may reduce responsiveness to normal neuropeptide signaling
- neuron damage
Causes a resistance to AgRP and POMC –> increase in body weight
High fat diet
Is ideally suited as a receptor site for body adiposity as well as for integration of hormonal and neural signals because its “leaky BBB” and location at the base of the hypothalamus
Arcuate nucleus
3% of subjects with severe early onset obesity have a __ mutation
Leptin receptor
Breaks down GLP-1
DPP-4
__ have been proven to have higher circulating leptin levels in proportion to fat mass when comparing them to their cohort
Females
Released postprandially from I cells in the small intestine
Reduces food intake through CCK1 receptors on the vagus nerve
CCK
For longer-term energy regulation, humoral signals derived from __ are integrated in specific regions of the hypothalamus
adipose tissue
Refers to the energy expenditure associated with digestion, absorption, and increased sympathetic nervous system activity after eating a meal
5-10% of TEE
Thermic effect of feeding (TEF)
Primary brain area regulating appetite and response to emotions
May mediate a hunger response even when an individual is not physically hunger
Amygdala
Day-to-day intake is primarily governed by which hormone?
Ghrelin
Leptin is a key regulator of signaling in the hypothalamic __ __
Arcuate nucleus (ARC)
Only gut derived signal that increases hunger
Ghrelin
Expressed in the CNS and in the distal ileum and colon
- rapidly released after food ingestion into the circulation in response to nutrient uptake
Incretin hormone - controls blood sugar by stimulating insulin secretion and inhibiting both glucagon secretion and gastric emptying
GLP-1
2 neuropeptides that leptin acts to release from the arcuate nucleus
- anorexigenic
POMC (turns into alpha-MSH)
CART
Mechanoreceptors and chemoreceptors in the GI tract signal through the __ to the brainstem for short-term regulation of appetite (hunger and satiety).
Vagal nerve
Leptin system is more effective in signaling __ of energy stores and less effective in signaling energy surplus
Depletion
Acts as an inverse agonist on constitutively active MC4 receptors
During a negative energy balance, __ neurons are activated and act to suppress the MC receptor activity
AgRP
__ is associated with metabolic regulation in gut hormones that are intended to drive energy stores back to initial replete levels
Weight loss
Obesity is associated with __
As BMI increases, leptin increases
- saturation occurs at a certain level
Leptin resistance
The default in the brain is the __ system
- this is due to evolution’s priority on eating to stay alive
Orixogenic (hunger)
Peptide hormone released from the fundic region of the stomach
Endogenous ligand for the growth hormone -secretagogue receptor (GHS-R)
Only known factor to increase appetite
Increased by fasting, fall after a meal
Ghrelin
6% of children with severe obesity have a mutation in the __
MC4 receptor
Lesions to the __ hypothalamus induce loss of appetite
Lateral
__ administration has been shown to reduce food intake mediated through both peripheral and central mechanisms, via projection to the hypothalamus and brainstem areas
Mimetic agents are used as drugs for Type 2 diabetes and cause weight loss
GLP-1
Has a reproductive function by letting the brain known that menstruation can begin because body fat starts to accumulate during pregnancy
Leptin
Result of a volitional mechanical work
- exercise
- daily activities
Also, result of nonvolitional mechanical work
- fidgeting
- maintaining posture
- spontaneous muscle contractions
15-30% of TEE
Physical activity
Despite the elevated secretion and circulation of __ in obesity, CNS levels do not rise proportionately due to saturation of the leptin receptor and reduced intracellular signaling
Thus, the CNS does not properly sense the expanded adipose mass
Leptin
Refers to the energy expended for normal cellular and organ function during post-absorptive resting conditions
Comprises 65% of TEE
Can be clinically measured by indirect calorimetry
RMR (Resting metabolic rate)
Pathways consist of dopaminergic neurons which originate in the ventral tegmental area and substantia nigra in the midbrain and project throughout the brain
Responsible for “liking, wanting, and craving of food”
- responsible for food-seeking behavior
Hedonic System (reward center)
Receptors that mediate the effects of __ belong to the NPY receptor family with high affinity for the NPY2R in the arcuate nucleus
PYY
Adipose-derived satiety hormone
- secreted in diurnal rhythm
Receptor in the CNS is a member of the IL-6 receptor family of type I cytokine receptors
Leptin
Comprised of 3 components:
- Resting metabolic rate (RMR)
- Thermic effect of feeding (REF)
- Energy expenditure of physical activity (PA)
Daily total energy expenditure (TEE)
Neuroendocrine peptide that is co-secreted together w/ insulin from pancreatic islet beta-cells
Plasma levels increase in response to nutritional stimuli
Inhibits gastric emptying and glucagon secretion and reduces short-term food intake
Directly stimulates neurons in the area postrema of the hindbrain
Mimetic agents used as a DM medication and cause weight loss
Amylin
Produced from the ob gene expressed in adipose cells
Communicates the status of energy stores to the brain
Leptin
2 neuropeptides that leptin acts to inhibit in the arcuate nucleus
- orixogenic
AgRP and NPY
Injury or lesions in the hypothalamus may result in a pattern of weight gain that is characterized as abrupt in onset and rapidly accelerating
Causes include:
- craniopharyngioma
- head trauma
- sarcoidosis
- aneurysm
- meningioma
- metastasis
- surgery
- radiation
Hypothalamic obesity
