10. The endocrine regulation of energy balance Flashcards
what are our sources pf ENERGY INPUT
food & drink
what are our sources of ENERGY OUTPUT (3)
RESTING METABOLISM
THERMIC EFFECT of FOOD
ACTIVITY
what factors INFLUENCE ENERGY BALANCE
BIOLOGICAL (inherited or
acquired – eg drugs, disease)
PSYCHOLOGICAL (affect CNS)
SOCIAL (affect CNS)
if you intake 100 kcal excess every day, how many extra kcal & kg of fat in a year?
36,500 kcal
5kg of extra fat
how is ENERGY EXPENDITURE in HEAVIER people
EXPEND MORE ENERGY
how do you measure ENERGY EXPENDITURE
whole-body calorimeter
REGULATION of FOOD INTAKE is largely CONTROLLED by…
the CNS
- particularly HYPOTHALAMUS
Food Intake can be modified by HEDONIC FACTORS:
TASTE
MEMORY
BEHAVIOURAL FACTORS
what are APETITE SIGNALS
FALLING GLUCOSE
FALLING NUTRIENTS (other)
GHRELIN (Increases) from stomach
what INDICATE FULLNESS
stomach STRETCHING
absorbing of NUTRIENTS
CHEMORECEPTORS (detect nutrients)
GUT HOROMES - tell brain we are full
what does GI TRACT do when regulating food intake
sends HORMONES & NEURAL SIGNALS via VAGUS NERVE or BLOOD to NTS of BRAIN
what area of the BRAIN receives hormones/neural signals from GI Tract and communicates with Hypothalamus
NTS
- NUCLEUS TRACTUS SOLLITARIUS
2 important NUCLEI of HYPOTHALAMUS in regulation of food intake
ARC
PVN
what are the ADIPOSITY SIGNALS in regulation of food intake
what are the ADIPOSITY SIGNALS in regulation of food intake
FAT MASS
what is the MAIN SIGNAL indicating FAT MASS in regulation of food intake
LEPTIN
what are the GUT HORMONES in regulation of food intake
- AMYLIN
- CHOLECYSTOKININ
(also stimulates gallbladder contractions after a meal) - GLP-1 : GLYCOGEN-LIKE PEPTIDE 1
(also stimulates insulin secretion after a meal) - PYY : PEPTIDE YY
what is the STOMACH HORMONE that STIMULATES APPETITE & INCREASES FOOD INTAKE
GHRELIN
what does GHRELIN also promote
FAT STORAGE
GHRELIN also has a role in regulation of …. release
GROWTH HORMONE RELEASE
GHRELIN RECEPTORS AKA
GHS-R
GROWTH HORMONE SECRETAGOGUE RECEPTOR
where do you find GHRELIN RECEPTORS / GHS-R
NPY/AgRP NEURONES in HYPOTHALAMIC ARCUATE NUCLEUS (arc)
when do GHRELIN levels RISE
BEFORE a meal, when stomach is EMPTY
when do GHRELIN levels FALL
shortly AFTER a meal, when stomach is FULL
how does GHRELIN CHANGE with WEIGHT LOSS
after you LOSE weight:
HIGHER GHRELIN LEVELS
- therefore feel more HUNGRY (hard to maintain weight loss)
when does PYY 3-36 INCREASE
AFTER MEALS (feel FULL)
how are PYY levels in OBESE people as opposed to lean people
LOW
- therefore feel HUNGRY
affects of GLP-1 in food intake
- REDUCES FOOD INTAKE
- ACTIVATES BRAIN areas involved in SATIETY : NEURONS in PVN and AMYGLADA
what is another SIGNAL of SATIETY that helps DECREASE FOOD INTAKE
INSULIN
- ANOREXIGENIC EFFECT
INSULIN secreted by
PACREATIC BETA CELLS
what does INSULIN SIGNAL to the HYPOTHALAMUS
that you are FED / FULL
INSULIN has what effect
ANOREXIGENIC EFFECT - decrease food intake
where are INSULIN RECEPTORS HIGHLY EXPRESSED
CNS
especially in:
- OLFACTORY BULBS
- HYPOTHALAMIC ARCUATE NUCLEUS
what happens when there is a NEURON-SPECIFIC DISRUPTION of INSULIN RECEPTOR GENE
INCREASED FOOD INTAKE & OBESITY
- with INCREASED BODY FAT & PLASMA LEPTIN LEVELS
what is a KEY HYPOTHALAMIC NUCLEUS in the REGULATION of APPETITE
hypothalamic ARCUATE NUCLEUS (ARC)
also
Ventromedial Nucleus
how does GHRELIN INCREASE FOOD INTAKE
STIMULATES NPY in ARC
- activates NPY Y5 RECEPTORS in PVN
- increased food intake
how does PYY INHIBIT FOOD INTAKE
INHIBITS NPY
inhibits activation of NPY Y5 RECEPTORS
NPY NEURONES in ARCUATE nucleus ACTIVATE NPY Y5 RECEPTORS in PVN to..
INCREASE FOOD INTAKE
(& INHIBIT MC4 & CART RECEPTORS)
POMC CART NEUROTENSIN ACTIVATES MC4 (melanocortin 4) RECEPTOR / CART RECEPTOR to…
DECREASE FOOD INTAKE
(inhibitory mechanism)
how does GLP-1 DECREASE FOOD INTAKE
INHIBITS NPY
ACTIVATES POMC CART
how does LEPTIN DECREASE FOOD INTAKE
ACTIVATES POMC CART
- ACTIVATES MC4 & CART RECEPTORS
& INHIBITS NPY
what does CLEAVAGE of POMC produce
MELANOCORTINS
how do we get CLEAVAGE of POMC
by PROHOMONE CONVERTASES: PC1 & PC2
what does targeted DELETION of MC4-R result in (in mice)
HYPERPHAGIA (excessive eating) & OBESITY
ADIPOSE TISSUE is LOOSE CONNECTIVE TISSUE comprising of: (2)
- ADIPOCYTES
- STROMOVASCULAR CELLS
(and immune cells)
ADIPOCYTES make up what proportion of our total cells
20-40%
majority is WHITE ADIPOSE CELLS
STROMOVASCULAR COMPONENT of ADIPOSE TISSUE consists of:
- ADIPOSE PRECURSORS
- VASCULAR cells
- IMMUNE cells
- FIBROBLASTS
- NERVE cells
ADIPOCYTES are …. CELLS
LIPID-STORING cells
Safely STORE excess calories - overnutrition
- Free fatty acids (FFAs) and their products can be toxic when stored elsewhere
ADIPOCYTES release..
energy-nutritional deprivation
- RESERVE when levels are low
what happens in ADIPOCYTES during POST-PRANDIAL PHASE (after eating)
LIPOGENESIS
FREE FATTY ACIDS are ESTERIFIED to TRIGLYCERIDES / triacylglycerols TAGs
(glucose converted to glycerol, merges with ffa)
stored in adipose tissue
(under influence of insulin)
what happens in ADIPOCYTES during FASTING (low insuline)
TAGs/TRIGLYCERIDES HYDROLYSED to FREE FATTY ACIDS and GLYCEROL
LIPASE activated
- used as a source of ENERGY
ADIPOSE TISSUE also acts as an…
ENDOCRINE ORGAN
secretes ADIPOKINES
ADIPOKINES/HORMONES secreted by ADIPOSE TISSUE
IL-6
TNF ALPHA
- inflammatory mediators
PAI
- modifies blood coagulation
ANGIOTENSINOGEN
- regulates vascular tone
LEPTIN
- appetite regulation
ADIPONECTIN
- insulin sensitivity
what is the main FUNCTION of LEPTIN
DECREASE FOOD INTAKE
where is LEPTIN almost exclusively expressed
ADIPOSE TISSUE
what is LEPTIN
SMALL POLYPEPTIDE
- 167 amino acids
LEPTIN is encoded by which gene
LEP GENE
aka Ob gene
effect of FATTY FOODS on LEPTIN
causes LEPTIN RELEASE
due to increased blood lipids
another FUNCTION of LEPTIN
Regulates Activity of GONADAL and THYROID axis
MUTATION in LEPTIN GENE (LEP) or LEPTIN RECEPTOR GENE results in
INTENSE HYPERPHAGIA (intense overeating) and consequently OBESITY
what is ADIPONECTIN
highly secreted hormone from ADIPOSE TISSUE
- most ABUNDANT ADIPOKINE
FUNCTION of ADIPONECTIN
ENHANCES INSULIN SENSITIVITY
in LIVER and PERIPHERAL tissue
ADIPONECTIN acts via..
to enhance insulin sensitivity
ADIPOR1 & ADIPOR2 RECEPTORS
what is the correlation between ADIPOSE TISSUE and ADIPONECTIN
HIGHER ADIPOSE TISSUE LEVELS
= LOWER ADIPONECTIN secretion
Paradoxically for an adipocyte-derived hormone, expression and secretion is diminished in central obesity
ADIPONECTIN is an excellent biomarker for INSULIN RESISTANCE.
when there is LOW ADIPONECTIN…
HIGH INSULIN RESISTANCE
ADIPONECTIN SECRETION is STIMULATED by…
THIAZOLIDINEDIONES (antidiabetic
agents)
what are the 2 TYPES of ADIPOSE TISSUE
WHITE adipose tissue
BROWN adipose tissue
ROLE of WHITE ADIPOSE TISSUE
STORES (excess) ENERGY as triglycerides
& SECRETES SIGNALLING FACTORS that regulate APPETITE & ENERGY HOMEOSTASIS
- leptin & adiponectin
ROLE of BROWN ADIPOSE TISSUE
GENERATES BODY HEAT
- helps SURVIVE COLD TEMPERATURES
by transferring ENERGY FROM FOOD into HEAT
CELLS in WHITE ADIPOSE TISSUE contain…
a SINGLE LARGE FAT DROPLET
- which forces the NUCLEUS to be SQUEEZED into a THIN RIM at the PERIPHERY
WHITE ADIPOSE TISSUE responds to/ has RECEPTORS for…
INSULIN
SEX HORMONES
NORADRENALINE
GLUCOCORTICOIDS
what does BROWN ADIPOSE TISSUE consist of
SMALL LIPID DROPLETS
numerous IRON-RICH MITOCHONDRIA (gives brown appearance)
what gives BROWN ADIPOSE TISSUE its brown appearance
IRON-RICH MITOCHONDRIA
where is BROWN ADIPOSE TISSUE (BAT) adundant
in SMALL MAMMALS and NEWBORNS
(some found in adults)
OBESITY is associated with
INCREASE in ADIPOSE TISSUE MASS
OBESITY occurs as a result of…
chronic IMBALANCE between ENERGY INTAKE and EXPENDITURE
involves interaction between GENETIC and ENVIRONMENTAL FACTORS
GENETIC OBESITY CAUSES
- Leptin deficiency
- Leptin Receptor deficiency
- deficiency in production of alpha MSH due to problems in POMC
- deficiency in PC1 enzyme (POMC to MC4 receptor)
- Mutations in MC4 Receptor
EFFECTS of WEIGHT LOSS from Dieting
- DECREASED LEPTIN
- DECREASED PYY & GLP-1
- INCREASED GHRELIN
(feel hungry) - DECREASED ENERGY EXPENDITURE due to lower size
therefore hard to maintain weight loss
Examples of treatments for obesity
- drugs that modify appetite control
- LEPTIN TREATMENT
- Setmelanotide drug - MC4R RECEPTOR for MC4R deficiency
- Semaglutide - GLP1 AGONIST
(drugs that act on leptin pathway or melanocortin system)
what is the action of Melanocortin Peptides eg (alpha-melanocyte-stimulating hormone) MSH released from ARC POMC NEURONS
BINDS to MELANOCORTIN RECEPTORS - MC4-Rs
to INHIBIT FOOD INTAKE
