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Lecture 13

PSYC 342 Lecture Notes - Lecture 13: Menopause, Flutamide, Leptin Receptor

Course Code
PSYC 342
Jens C Pruessner

of 6
PSYC 342 Lecture 13 - Mar. 8
Eating & Eating Disorders:
Hedonic foods, such as chicken wings and cupcakes, that are high in fat and sugar, act on the reward pathway of the brain
and increase their incentive salience
Hedonic Feeding:
The maintenance of a steady state of an organism by physiological or behavioural feedback control mechanisms
Feeding behaviour is fundamentally governed by homeostasis, due to the body’s need to maintain an optimal energy “set
Evolutionarily speaking, humans were often in a state of starvation, so it was adaptive to prefer high sugar and fat foods.
However, in recent years, this adaptation with the dramatic increase in food supply has led to higher incidences of obesity
Orexigenic peptides: increase motivation to eat
E.g., ghrenlin, NPY, AgRP, MCH, Orexin A, Orexin B, Gallatin
Anorexigenic peptides: decrease motivation to eat
E.g., leptin, insulin, alpha-MSH, CRH, TRH, CART, POMC, GL-PI
A peptide hormone produced by the stomach cells; it is thought to increase feelings of hunger
Also an Orexigenic hormone (stimulating appetite)
May have evolved as a response to the feast or famine conditions of early humans
In recent years, however, this in direct conflict with the dangerous phenomenon of overeating in the developed world
Secreted from the stomach into the bloodstream, it travels to receptors in the brain to stimulate food intake
Also produced in the hypothalamic arcuate nucleus, it stimulates the secretion of growth hormone from the anterior pituitary
Also activates the mesolimbic cholinergic-dopaminergic reward link, a circuit that communicates the hedonic and reinforcing
aspects of natural rewards, such as food
Systematic injections of ghrelin stimulate food intake and increase body mass in rats
Increased hyperphagia, weight gain and adiposity occur after continuous systematic ghrelin administration at much lower
doses than previously thought
Findings point to a physiological role for circulation of ghrelin in the regulation of food
Blood concentrations of ghrelin levels increase nearly twofold immediately before
each meal and fall within one hour after eating
Ghrelin levels showed a diurnal rhythm that is exactly in phase with that of leptin - ris-
ing and falling at the same times during the day
This rise and fall supports the hypothesis that ghrenlin plays an important role in
mean initiation in humans
Prader Willi Syndrome:
Genetic disorder with mild growth retardation
Hyperphagia and obesity common
Fasting plasma ghrelin levels elevated
Leptos: “thin”
Adipokine Hormone
Produced in fat (adipose) tissue
Levels are higher in larger people, and after meals, and lower in thinner people
and during fasting periods
Actions of Leptin:
Active transport mechanism brings leptin across BBB
Binds to receptors in hypothalamus to inhibit eating and send satiety signals
Leptin levels are proportional to body fat
High while fat is being stored
Fall rapidly when fat begins to be metabolized
High levels of lepton cause long-term satiety
Rodent Studies:
Mutations in mice in genes coding for leptin (“ob”) or leptin receptors “db”
Leptin treatment of ob/ob mice caused significant weight loss
Mutation of both leptin and leptin receptor genes have been found in humans, though very rare
The ob(lep) gene is found on chromosome 7
Can be treated with daily leptin injections
Farooqi et al, 2005:
As Leptin cannot cross the blood brain barrier by itself, obesity may be a result of a malfunction of an active transfer mecha-
Obese people exhibit heightened levels of blood leptin, which does not appear to be absorbed into the CNS
Aging may also contribute to leptin resistance
Study by Dalton et al in 2003 showed that when rats are chronically stressed (and maybe people), they crave high-fat foods
in an attempt to reduce anxiety...this may explain some parts of the epidemic of obesity occurring in Western culture
Dalton’s suggests that glucocorticoids work differently in the long term than in the short term chronic release of glucocorti-
coids and CRH drive stressed individuals to seek out pleasurable foods which leads to weight gain
Both hedonic feeding and homeostasis are important for the regulation of human food intake via anorexigenic and orexigenic
Ghrelin is an orexigenic hormone produced by the stomach and arcuate nucleus
Leptin is an anorexigenic hormone produced by fat cells; dysregulation can lead to obesity; obese individuals may have lep-
tin resistance
Insulin is an anorexigenic hormone produced by the pancreas that regulates long-term patterns of food intake
Evidently, feeding is a complex process regulated by many hormones. Researchers are still in the process of finding out how
we can use them to tackle issues such as obesity
Eating Disorders: Anorexia & Bulimia
What is Anorexia Nervosa?
What is Bulimia Nervosa?
Gender ratios
Hormonal factors affecting gender ratios
Environmental factors affecting gender ratios
Anorexia Nervosa: DSM IV Criteria
Refusal to maintain body weight at or above a minimally normal weight for age and height
Intense fear of gaining weight or becoming fat, even though underweight
Disturbance in the way in which one’s body weight or shape is experienced, undue influence of body weight or shape on
self-evaluation, or denial of the seriousness of the current low body weight
In postmenarcheal females, amenorrhea, i.e., the absence of at least three consecutive menstrual cycles
Anorexia Nervosa: The Facts
Symptoms associated with AN seem to have existed as far back as the 1600s
Individuals with AN tend to be highly perfectionist
Only psychiatric disorder in the DSM-IV that requires an endocrine dysfunction as criteria for diagnosis (menstrual abnormal-
10% diagnosed die
Alterations Observed in Anorexia Nervosa:
Oligomenorrhea (irregular menstrual cycles)
Delayed puberty
Hypercortisolism (elevated cortisol)
Increased CRH in the CNS
Increased Basal/Pulsatile GnRH secretion
Increased Osteoporosis
Lower circulating leptin levels
Decreased Insulin secretion
Increased vasopressin in the CNS
Altered Melatonin levels
Bulimia Nervosa: DSM IV Criteria
Recurrent episodes of binge eating characterized by both:
Eating in a discrete period of time (e.g., within any 2-hour period), an amount of food that is definitely larger than most
people would eat during a similar period of time and under similar circumstances
A sense of lack of control over eating during the episode, defined by a feeling that one cannot stop eating or control
what or how much one is eating
Recurrent inappropriate compensatory behaviour to prevent weight gain
Self-induced vomiting
Misuse of laxatives, diuretics, enemas, or other medications
Excessive exercise
Clinical Correlates: