Neuroendocrinology of Energy Homeostasis Flashcards
What are 3 sources of metabolic fuel in the body?
Carbohydrate
Fat
Protein
What is energy balance achieved by?
Matching energy expenditure & food intake
What happened when rats had a lesion of lateral hypothalamus?
Lost weight
What happened when rats had a lesion of ventromedial hypothalamus?
Gained weight
What two things do neural pathways link?
Hypothalamic nuclei with each other & other brain centres
What are some hormones found in adipose tissue?
Leptin
IL-1
fatty acids
chemokines
adiponectin
What is leptin?
167aa peptide hormone
What is leptin secreted by?
Adipocytes
What does leptin function as?
Indicator of adiposity (energy stores)
How does leptin exerts its effect?
via a cell membrane receptor -> type 1 cytokine receptor family, JAK/STAT pathway
What is the only active leptin receptor?
LepRB (CNS)
What are some actions of leptin?
Food intake & energy expenditure matching
vascular function (atherosclerosis)
reproduction (placental function)
bone & cartilage (regulation of bone mass)
immune system modulation
also targets kidneys, bowel, pancreas, muscle
What happens in the ob/ob mouse?
null mutation of leptin gene (chr6) -> obesity & mild diabetes
What happened in the db/db mouse?
null mutation of leptin receptor gene -> obesity, fatal diabetes & hyperleptinemia
What is the difference between the mice and satiety factor?
db/db = overproduced satiety factor but couldn’t respond to it
ob/ob = responded to satiety factor but could not produce its own
Which stomach hormone is not a satiety factor?
Ghrelin
What is ghrelin?
peptide hormone (28aa) produced in P and D1 cells in fundus
What other cells is ghrelin found in?
Epsilon cells (islets of langerhans)
arcuate nucleus (hypothalmus)
What does ghrelin have an effect on?
increases glucose, lipid and energy metabolism in liver, adipose tissue & pancreas
What brain regions does ghrelin signal?
Hypothalamus
Hippocampus
ventral tegmentum & NA
brainstem
What is ghrelin synthesized as?
94 aa prohormone
What does processing yield?
Mature ghrelin & obestatin
What does the active form of ghrelin have?
n-octanoic acid moiety -> essential for receptor binding & crossing BBB
What does antagonism of ghrelin receptor reduce?
Food intake & body weight gain
What are the names for the feeding and satiety pathways?
orexigenic = feeding
anorexigenic = satiety
What happens if the MC4R melanocortin receptor is defective?
cause autosomal dominant obesity
What protein is a functional antagonist of the melanocortin 4 receptor?
Agouti related protein
What does overexpression of Agrp in transgenic mice cause?
Hyperphagia & obesity mimicing effect of MC4R deficiency
What brain regions do the feeding and satiety pathways signal to?
LHA
DMN
PVN
VMN
What two brain areas is the hypothalmus linked to?
Nucleus accumbens
Ventral tegmental area
What 3 things are the NA and VTA associated with?
Pleasure
reward
hedonic pathways
What system is found throughout the CNS and PNS?
Endogenous lipophilic cmpounds -> Endocannabinoid system
What processes are ECS implicated in?
Appetite regulation
pain-sensation
mood
memory
psychoactive effects of cannabis
Which EC receptor is the most abundant?
CB1 found in the brain & nervous system
highly expressed in NA
What is CB1’s endogenous ligand?
Anandamide & binds phytocannabinoid THC
What do endocannabinoids act as?
Appetite signals
What are exogenous cannabinoids?
Tetrahydrocannabinol
2 arachidonglycerol
What is a selective receptor blocker of CB1?
Rimonabant -> reduce food intake
What happens if FAAH is mutated?
Increased BMI as EC is not degraded
