Leptin and Energy Balance

Question 1

what is obesity

Answer 1

BMI greater than or equal to 30

Question 2

what are the health risks associated with obesity?

Answer 2

diabetes
all cancers
gall stones
hypertension
CV disease

Question 3

define body weight

Answer 3

function of energy intake balanced with energy expenditure

Question 4

energy intake

Answer 4

ingestion of protein/fat/carbohydrates

Question 5

energy expenditure

Answer 5

physical activity
diet-induced thermoregulation
basal metabolic rate

Question 6

treatment

Answer 6

reduce intake and increase expenditure

Question 7

what is the fat mass heritability

Answer 7

40-70%

Question 8

obesity in twins

Answer 8

non-identical twins have variations in body shape
obesity is driven by many genes

Question 9

obesogenic environment

Answer 9

slow evolutionary adaptation (genes prone to starvation)
rapid environmental change (sedentary lifestyle/motorised transport)
rapid behavioural change

Question 10

surgical options for treatment

Answer 10

gastric bypass (reduction by ~25%)
gastric sleeve (reduction by ~14%)

Question 11

pharmacological treatment

Answer 11

orlistat
most drugs removed from market since cause CV/psychiatric side effects

Question 12

homeostatic integrative centres

Answer 12

hypothalamus
brainstem

Question 13

ghrelin

Answer 13

meal initiator
increases food uptake TO hypothalamus
grumbling

Question 14

what is leptin

Answer 14

decreases food intake
secreted from fat stores

Question 15

PYY3-36

Answer 15

decreases food intake
TO

Question 16

GLP-1

Answer 16

releases insulin
contacts B cells to release insulin

Question 17

hypothalamus anatomy and location

Answer 17

located above pituitary gland
leaky BBB

Question 18

lesions which are an oversimplification

Answer 18

lateral area hypothalamus lesion causes hunger/weight loss
ventromedial area hypothalamus lesion causes satiation/obesity

Question 19

nuclei in the hypothalamus

Answer 19

obesity:
paraventricular nucleus (PVN)
ventromedial nucleus (VMN)
dorsomedial nucleus (DMN)

anorexia/weight loss:
lateral hypothalamic area (LHA)

arcuate nucleus (ARC)

Question 20

Ingalls AM et al., 1950 study

Answer 20

normal vs ob/ob mutant
3 weeks WT weighed 12g vs ob/ob 16g 10 weeks WT 29g ob/ob 90g
ob/ob mutant has early onset obesity, hyperphagia, decreased energy expenditure, hyperglycemia, adipocyte hyperplasia

Question 21

circulating factor mutants

Answer 21

ob/ob - no circulating factor, truncated leptin so cannot bind to receptor
db/db - defective leptin receptor (unresponsive to circulating factor)

Question 22

parabiosis experiment (fusing circulation of 2 mice)

Answer 22

ob/ob X WT ob/ob mouse loses weight because it receives functional leptin from WT
db/db X WT WT has excessive leptin WT starves to death
ob/ob X db/db ob/ob loses weight

Question 23

VMH lesion X lean control

Answer 23

control mouse stops eating

Question 24

leptin R mRNA location

Answer 24

VMN
DMN
ARC

Question 25

leptin

Answer 25

167 aa of cytokine family
expressed mainly in adipose tissue
levels of leptin = total fat mass
starvation reduces leptin
decreases food intake and adrenal corticosteroids

Question 26

what is the set point model

Answer 26

maintains constant body weight by controlling eating behaviour and burning excess fuel

Question 27

adiposity signalling by leptin

Answer 27

1) leptin correlates to body fat levels (circulated)
2) after eating elevated leptin stimulates energy expenditure and inhibits eating
3) fat mass decreases, serum leptin falls. feeding is stimulated and energy expenditure is suppressed
4) fat reserves return to set point

Question 28

hormonal effects of leptin

Answer 28

more leptin needed in puberty
excessive weight loss causes iregular periods

Question 29

leptin therapy in humans

Answer 29

blood leptin levels are higher in obese patients
clinical trials are uneffective - no weight loss after injection
only effective in rare humans with severe obesity

Question 30

leptin receptor

Answer 30

member of the cytokine family
expressed mostly in ARC, liver, muscles, adipose

Question 31

leptin signalling

Answer 31

leptin-LEPR
phosphorylation of PSTAT3
leptin binds to 2 JAK molecules and phosphorylates PSTAT3 and moves to nucleus

Question 32

anorexigenic and orexigenic peptides

Answer 32

anorexigenic peptides increases releases POMC CART
orexigenic peptides decreases releases NPY and AGRP