Hypothalamic Regulation of Appetite and Satiety
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Questions and Answers

Which of the following peptides is classified as orexigenic?

  • Insulin
  • Ghrelin (correct)
  • CART
  • Leptin

    • What is the effect of anorexigenic signals on energy expenditure?

  • Increase energy expenditure (correct)
  • Increase food intake
  • Increase energy storage
  • Decrease energy expenditure

    • Which neuropeptide is argued not to be a neuropeptide but plays a role in appetite regulation?

  • Neuropeptide Y (NPY)
  • Leptin (correct)
  • Melanocyte Stimulating Hormone (αMSH)
  • Ghrelin

    • What is the primary role of αMSH in the hypothalamus?

    <p>Inhibit food intake</p> Signup and view all the answers

    How does fasting affect POMC gene expression?

    <p>Decreases expression</p> Signup and view all the answers

    Which receptor subtype is primarily associated with melanocortin in the brain?

    <p>MC-3</p> Signup and view all the answers

    What effect do orexigenic signals have on energy storage?

    <p>Increase energy storage</p> Signup and view all the answers

    Which peptide is considered anorexigenic and acts to reduce food intake?

    <p>PYY3-36</p> Signup and view all the answers

    What role do synthetic agonists play in food intake regulation?

    <p>They suppress food intake.</p> Signup and view all the answers

    Which receptor deletion is primarily associated with obesity in mice?

    <p>MC-4 receptor.</p> Signup and view all the answers

    What is the primary effect of Neuropeptide Y (NPY) when injected into the hypothalamus?

    <p>Stimulates food intake.</p> Signup and view all the answers

    What type of peptides are predominantly involved in anorexigenic signaling?

    <p>Regulatory hormones.</p> Signup and view all the answers

    Which substance causes long-lasting hyperphagia when administered intracerebroventricularly?

    <p>Agouti-related Protein (AgRP).</p> Signup and view all the answers

    What characterizes mice that lack NPY receptor subtypes Y1 or Y5?

    <p>They are predisposed to obesity.</p> Signup and view all the answers

    Which of the following is considered to be orexigenic?

    <p>Neuropeptide Y (NPY).</p> Signup and view all the answers

    Which neuropeptide is most abundant in the human brain?

    <p>Neuropeptide Y (NPY).</p> Signup and view all the answers

    What is the primary function of leptin in the context of energy balance?

    <p>Inhibiting food intake and decreasing body weight</p> Signup and view all the answers

    Which of the following accurately describes the source of insulin in the body?

    <p>Secreted from the pancreas in relation to blood glucose levels</p> Signup and view all the answers

    Which neuropeptide is classified as orexigenic?

    <p>Ghrelin</p> Signup and view all the answers

    What is a significant effect of neuronal deletion of the leptin receptor (Ob-Rb)?

    <p>Increased appetite and resulting obesity</p> Signup and view all the answers

    What regulatory role does leptin NOT play in the body?

    <p>Stimulating fat deposition</p> Signup and view all the answers

    Which peptide is produced exclusively in the hypothalamus rather than peripheral tissues?

    <p>NPY</p> Signup and view all the answers

    Which statement about the effects of insulin in the hypothalamus is true?

    <p>It inhibits food intake and decreases body weight</p> Signup and view all the answers

    Which biological function is primarily associated with leptin?

    <p>Control of appetite and energy expenditure</p> Signup and view all the answers

    Which peptide is primarily produced and secreted by the endocrine mucosal L-cells of the gastrointestinal tract?

    <p>Glucagon-like peptide 1 (GLP-1)</p> Signup and view all the answers

    What is the main action of Peptide YY (PYY 3-36)?

    <p>Inhibits gastric motility</p> Signup and view all the answers

    Which orexigenic peptide is NOT classified as a neuropeptide?

    <p>Ghrelin</p> Signup and view all the answers

    What stimulus leads to the release of Cholecystokinin (CCK)?

    <p>Lipids and proteins in a meal</p> Signup and view all the answers

    Which of the following statements accurately describes Oxyntomodulin (OXM)?

    <p>Suppresses appetite with an unclear mechanism</p> Signup and view all the answers

    Which anorexigenic signal is released from enteroendocrine cells of the duodenum?

    <p>Glucagon-like peptide 1 (GLP-1)</p> Signup and view all the answers

    What is the primary function of ghrelin?

    <p>Stimulates hunger</p> Signup and view all the answers

    What is the role of obestatin in relation to ghrelin?

    <p>It antagonizes ghrelin's effects on food intake</p> Signup and view all the answers

    What is the primary role of leptin in energy balance?

    <p>Reduces appetite by signaling fullness to the brain</p> Signup and view all the answers

    What genetic mutation is responsible for obesity in the db/db mouse model?

    <p>Mutation in the leptin receptor gene</p> Signup and view all the answers

    How does the Ay mutation affect obesity in mice?

    <p>Antagonizes MC-4 receptor, leading to obesity</p> Signup and view all the answers

    What is the biochemistry behind the Zucker fa/fa rat's obesity?

    <p>Loss of function of the leptin receptor</p> Signup and view all the answers

    Which of the following describes the relationship between obesity genes in humans and corresponding mouse models?

    <p>LepR mutations in humans and mice exhibit similar obesity characteristics</p> Signup and view all the answers

    What is the impact of the Ob gene mutation in Ob/Ob mice?

    <p>Decreased leptin production</p> Signup and view all the answers

    Which receptor is directly affected by the agouti protein?

    <p>MC-4 receptor</p> Signup and view all the answers

    How does fasting influence leptin levels?

    <p>It decreases leptin levels.</p> Signup and view all the answers

    What characterizes the function of CPE (carboxypeptidase E) in obesity?

    <p>Affects the processing of multiple hormones</p> Signup and view all the answers

    What is a significant physiological outcome observed in Ay heterozygotes?

    <p>Hyperglycemia</p> Signup and view all the answers

    Study Notes

    Hypothalamic regulation - Appetite and Satiety

    • Hypothalamus regulates food intake and energy expenditure through short-term and long-term processes
    • Short term processes regulate meal initiation, termination and inter-meal frequency
    • Long term processes regulate body weight and food intake

    Neuropeptides and Obesity

    • Hypothalamic regulation of food intake and body weight is influenced by neuropeptides
    • Neuropeptides can be produced and released intrinsically in the hypothalamus or produced and secreted peripherally and access hypothalamus
    • Orexigenic neuropeptides increase food intake and energy storage and decrease energy expenditure
    • Anorexigenic neuropeptides decrease food intake and energy storage and increase energy expenditure
    • Examples of orexigenic neuropeptides include NPY, GALANIN, MCH, OREXINS, AGOUTI, GHRELIN, ENDOCANNABINOIDS
    • Examples of anorexigenic neuropeptides include LEPTIN, INSULIN, a-MSH, CART, GLP-1, TRH, CRH, PYY3-36

    Melanocortins – αMSH

    • αMSH (α melanocyte stimulating hormone) is formed by sequential cleavages of the proopiomelanocortin (POMC) precursor polypeptide
    • POMC gene expression is reduced on fasting and increased following attainment of a positive energy balance
    • αMSH levels are high in the hypothalamus and this peptide inhibits food intake (anorexigenic)
    • Melanocortin receptor subtypes MC-3 & MC-4 are mainly expressed in the brain
    • Synthetic agonists and antagonists to these receptors suppress and enhance food intake respectively
    • Deletion of MC-4 or MC-3 receptor produces obesity in mice

    Neuropeptide Y (NPY)

    • NPY is a 36 aa peptide and one of the most abundant in the human brain. A significant number of NPY-containing neurons exist in the arcuate nucleus (ARC)
    • Injection of NPY into the hypothalamus stimulates food intake and reduces energy expenditure (orexigenic)
    • Repeated administration of NPY leads to obesity
    • NPY receptor antagonists attenuate feeding and reduce obesity
    • Mice lacking NPY receptor subtypes, Y1 or Y5 are pre-disposed to obesity
    • AgRP co-expresses with NPY in ARC neurons
    • AgRP and Agouti (Ay) are antagonists to MC3 and MC4 receptors
    • Intracerebroventricular (ICV) AgRP causes long-lasting hyperphagia (Orexigenic)

    Adiposity signals – Leptin

    • Leptin is a member of the cytokine family, 146 aa long, made and secreted from adipocytes
    • Leptin circulates in proportion to fat mass (adiposity)
    • A specific transport system exists for leptin to enter the brain
    • High levels of leptin receptors (Ob-Rb) are expressed on hypothalamic ARC neurons.
    • ICV leptin inhibits food intake and decreases body weight of rodents
    • Neuron-specific deletion of the leptin receptor (Ob-Rb) results in obesity

    Biological Roles of Leptin

    • Leptin plays a role in food intake, energy expenditure, fat deposition, peripheral glucose homeostasis, insulin sensitivity, maintenance of the immune system, maintenance of the reproductive system, angiogenesis, tumorigenesis and bone formation.

    Adiposity signals – Insulin

    • Insulin circulates in proportion to adiposity, although it is secreted from the pancreas
    • A transport system for insulin to enter the brain exists
    • High levels of insulin receptors are expressed in the hypothalamus, most notably in the ARC
    • ICV insulin inhibits food intake and decreases body weight of rodents
    • Neuron-specific deletion of the insulin receptor results in obesity
    • Peripheral actions of insulin are opposite

    Satiety Signals

    • Satiety signals are released in response to food ingestion and act to reduce food intake and decrease energy expenditure
    • CCK (Cholecystokinin) is released from enteroendocrine cells of the duodenum and jejunum in proportion to lipids and proteins in a meal. It signals via sensory nerves to the hindbrain and directly to the hindbrain (nucleus of solitary tract – NTS)
    • PYY 3-36 (Peptide YY) is released from endocrine mucosal L-cells of the G-I tract and increases rapidly postprandially. It inhibits gastric motility, slows emptying and reduces food intake (Hypothalamus)
    • GLP-1 (Glucagon-like peptide 1) is released from L-cells of the G-I tract in response to food ingestion. It inhibits gastric emptying and reduces food intake (Hypothalamus and NTS)
    • OXM (Oxyntomodulin) is released after the meal from oxyntic and L-cells of the small intestine. It acts to suppress appetite, although the mechanism and site are unclear.
    • Obestatin is released in response to ingestion from cells lining the stomach and small intestine. It reduces food intake.
    • Ghrelin is an octanoylated peptide produced by oxyntic cells in the stomach. It is a powerful orexigenic peptide that stimulates food intake and decreases fat utilization by acting on the growth hormone secretagogue receptor (GHSR)

    Models of Obesity

    • Rodent models of obesity are important for elucidating neural pathways of energy balance and play a key role in obesity research
    • Monogenic mutations in mouse strains resulting in obesity have been identified and these genes are crucial elements of physiological pathways for energy balance control
    • Ob/Ob mouse spontaneously develops obesity through a mutation in the Ob gene, which codes for leptin. Reduced leptin mimics starvation and causes unrestrained appetite.
    • db/db mouse spontaneously develops obesity through a mutation in the db gene, which codes for the leptin receptor (Ob-R). The mutation prevents the formation of Ob-Rb, leading to obesity.
    • Ay mutation (Agouti yellow) leads to obesity through ubiquitous ectopic expression and acts as an antagonist for hypothalamic MC-4 receptor.

    Mouse models of obesity

    • Mouse models are used to study the role of different genes in obesity
    • In the Zucker fa/fa rat, a mutation in the Ob-R gene results in a dysfunctional leptin receptor, causing obesity and leptin resistance.
    • In the db/db mouse, a mutation in the Ob-R gene results in a dysfunctional leptin receptor, causing obesity and leptin resistance.
    • In the Ob/Ob mouse, a mutation in the Ob gene causes a deficiency in leptin production, resulting in obesity.
    • In the fat/fat mouse, a loss of function mutation in the CPE gene (carboxypeptidase E) results in a deficiency in α-MSH production, leading to obesity.

    Rodent mutations in the signalling pathway

    • Rodent mutations in genes involved in the leptin-melanocortin signalling pathway are crucial for understanding how the hypothalamus regulates energy balance
    • These mutations affect the production and function of key proteins, including leptin, leptin receptor, POMC, AgRP, α-MSH and MC4-R

    Parallels between Mouse Models and Humans

    • The leptin receptor (Ob-R) gene, POMC gene and MC4-R gene are found in both humans and mice.
    • Mutations in these genes can lead to obesity in both humans and mice

    Searching for human obesity genes

    • Monogenic causes for obesity are rare in humans but are important for understanding the underlying genetic mechanisms.
    • Ob mutations are extremely rare in humans.
    • Truncated leptin receptor (Ob-R) has been reported in humans.
    • Loss of Function POMC mutations are relatively rare, but are present in humans.

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    Hormonal Regulation of Appetite and Satiety PDF

    Description

    Explore the role of the hypothalamus in regulating appetite and satiety through various neuropeptides. This quiz covers both short-term and long-term processes that influence food intake and energy expenditure. Discover the distinctions between orexigenic and anorexigenic neuropeptides and their impact on body weight.

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