MCP Lecture 9 Flashcards
How do you measure BMI?
kg/m2
What is obesity a risk factor for?
- psychological stress
- obstructive sleep apnea
- joint diseases, gallbladder disease, reproductive disorders
- 20% cancer death
- cardiovascular disease
- type II diabetes
What factors effect obesity?
- genetics (polygenic)
- environment (diet, exercise)
- gut microflora
- number of adipocytes established early in life
How does the fat-to-brain signaling system work?
- leptin hormone-like signal released from adipocytes
- goes to hypothalamic leptin receptors
- hypothalamic centers influence energy intake and energy expenditure through effector molecules
What does the ob gene encode for?
the protein/hormone leptin
behave as if starved (decreased body temp, energy expenditure, immune function, infertility, increased feeding)
if leptin is given, mouse becomes less obese effects reversible
What does the db gene encode for?
leptin receptor
give extra leptin, continues to become more obese
What are orexigenic effectors? What neurons release them?
substances that stimulate food intake
AgRP neurons
What are anorexigenic effectors? What neurons release them?
substances that promote lower food intake
POMC neurons
What are long term, short term, and medium term signals that influence appetite and energy expenditure through neuronal activities in the brain?
long term: leptin
short term: cholecyskinin
medium term: PYY
What happens to leptin levels in obese people?
leptin levels extremely high - develop leptin resistance so leptin has limited role in body weight control
What are the five main components of energy expenditure?
- resting energy expenditure (or basal metabolic rate)
- energy expended in digesting, metabolizing, storing food
- volitional exercise: mechanical and thermic
- nonexercise activity thermogenesis (typing, walking)
- adaptive (faculative) thermogenesis
What are forms of adaptive (facultative) thermogenesis?
- shivering (skeletal muscle) bc cold
- nonshivering - brown fat tissue - uncoupling proteins
What are the three types of adipocytes?
- white fat cells - fat storage and body insulation
- brown fat cells - heat production - uncoupling protein
- beige fat cells - white adipose tissue that has been partially converted
What is the uncoupling protein and how does it work?
UCP1 - mitochondria
allows proton leak pathways without being coupled with ATP synthesis
-adaptive thermogenesis because energy is released as heat
What are proteins with similar function to UCP1 to increase uncoupling? Examples?
membrane proteins (adenine nucleotide translocase ANT in skeletal muscle) protonophores (poke hole in membrane - 2,4-dinitro-pheno DNP)
How is UCP1 activated?
- by fatty acids
in response to cold and overfeeding - sympathetic neurons release catecholamines to activate the receptores, increasing lipolysis and releases FA activating UCP1 - nuclear receptors such as PPARgamma and retinoic acid receptor
What is MC4R?
melanocortin 4 receptor
involved in appetite regulation
What does a mutation in KSR2 cause? Why?
severe early-onset obesity
KSR2 activates AMPK which increases FA and glucose oxidation and decreases energy storage
What does dinitrophenol do?
anti-obesity drug that increases energy expenditure
also thyroid hormone
What does phentermines do?
anti-obesity drug that reduces feeding by controlling activity of neural circuit
What does orlistat do?
interferes with fat absorption
What does locarserin do?
promotes satiety by activating serotonin receptors in the brain
What does qysmia do?
combination of phentermine and topiramate (anti-epileptic
drug)
