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ENDOCRINOLOGY > 10. The endocrine regulation of energy balance > Flashcards

10. The endocrine regulation of energy balance Flashcards

1
Q

what are our sources pf ENERGY INPUT

A

food & drink

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2
Q

what are our sources of ENERGY OUTPUT (3)

A

RESTING METABOLISM

THERMIC EFFECT of FOOD

ACTIVITY

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3
Q

what factors INFLUENCE ENERGY BALANCE

A

BIOLOGICAL (inherited or
acquired – eg drugs, disease)

PSYCHOLOGICAL (affect CNS)

SOCIAL (affect CNS)

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4
Q

if you intake 100 kcal excess every day, how many extra kcal & kg of fat in a year?

A

36,500 kcal
5kg of extra fat

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5
Q

how is ENERGY EXPENDITURE in HEAVIER people

A

EXPEND MORE ENERGY

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6
Q

how do you measure ENERGY EXPENDITURE

A

whole-body calorimeter

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7
Q

REGULATION of FOOD INTAKE is largely CONTROLLED by…

A

the CNS
- particularly HYPOTHALAMUS

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8
Q

Food Intake can be modified by HEDONIC FACTORS:

A

TASTE
MEMORY
BEHAVIOURAL FACTORS

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9
Q

what are APETITE SIGNALS

A

FALLING GLUCOSE
FALLING NUTRIENTS (other)

GHRELIN (Increases) from stomach

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10
Q

what INDICATE FULLNESS

A

stomach STRETCHING
absorbing of NUTRIENTS
CHEMORECEPTORS (detect nutrients)
GUT HOROMES - tell brain we are full

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11
Q

what does GI TRACT do when regulating food intake

A

sends HORMONES & NEURAL SIGNALS via VAGUS NERVE or BLOOD to NTS of BRAIN

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12
Q

what area of the BRAIN receives hormones/neural signals from GI Tract and communicates with Hypothalamus

A

NTS
- NUCLEUS TRACTUS SOLLITARIUS

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13
Q

2 important NUCLEI of HYPOTHALAMUS in regulation of food intake

A

ARC
PVN

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14
Q

what are the ADIPOSITY SIGNALS in regulation of food intake

A
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15
Q

what are the ADIPOSITY SIGNALS in regulation of food intake

A

FAT MASS

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16
Q

what is the MAIN SIGNAL indicating FAT MASS in regulation of food intake

A

LEPTIN

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17
Q

what are the GUT HORMONES in regulation of food intake

A
  • 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
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18
Q

what is the STOMACH HORMONE that STIMULATES APPETITE & INCREASES FOOD INTAKE

A

GHRELIN

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19
Q

what does GHRELIN also promote

A

FAT STORAGE

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20
Q

GHRELIN also has a role in regulation of …. release

A

GROWTH HORMONE RELEASE

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21
Q

GHRELIN RECEPTORS AKA

A

GHS-R
GROWTH HORMONE SECRETAGOGUE RECEPTOR

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22
Q

where do you find GHRELIN RECEPTORS / GHS-R

A

NPY/AgRP NEURONES in HYPOTHALAMIC ARCUATE NUCLEUS (arc)

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23
Q

when do GHRELIN levels RISE

A

BEFORE a meal, when stomach is EMPTY

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24
Q

when do GHRELIN levels FALL

A

shortly AFTER a meal, when stomach is FULL

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25
Q

how does GHRELIN CHANGE with WEIGHT LOSS

A

after you LOSE weight:
HIGHER GHRELIN LEVELS
- therefore feel more HUNGRY (hard to maintain weight loss)

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26
Q

when does PYY 3-36 INCREASE

A

AFTER MEALS (feel FULL)

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27
Q

how are PYY levels in OBESE people as opposed to lean people

A

LOW
- therefore feel HUNGRY

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28
Q

affects of GLP-1 in food intake

A
  • REDUCES FOOD INTAKE
  • ACTIVATES BRAIN areas involved in SATIETY : NEURONS in PVN and AMYGLADA
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29
Q

what is another SIGNAL of SATIETY that helps DECREASE FOOD INTAKE

A

INSULIN

  • ANOREXIGENIC EFFECT
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30
Q

INSULIN secreted by

A

PACREATIC BETA CELLS

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31
Q

what does INSULIN SIGNAL to the HYPOTHALAMUS

A

that you are FED / FULL

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32
Q

INSULIN has what effect

A

ANOREXIGENIC EFFECT - decrease food intake

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33
Q

where are INSULIN RECEPTORS HIGHLY EXPRESSED

A

CNS
especially in:
- OLFACTORY BULBS
- HYPOTHALAMIC ARCUATE NUCLEUS

34
Q

what happens when there is a NEURON-SPECIFIC DISRUPTION of INSULIN RECEPTOR GENE

A

INCREASED FOOD INTAKE & OBESITY
- with INCREASED BODY FAT & PLASMA LEPTIN LEVELS

35
Q

what is a KEY HYPOTHALAMIC NUCLEUS in the REGULATION of APPETITE

A

hypothalamic ARCUATE NUCLEUS (ARC)

also
Ventromedial Nucleus

36
Q

how does GHRELIN INCREASE FOOD INTAKE

A

STIMULATES NPY in ARC
- activates NPY Y5 RECEPTORS in PVN

  • increased food intake
37
Q

how does PYY INHIBIT FOOD INTAKE

A

INHIBITS NPY
inhibits activation of NPY Y5 RECEPTORS

38
Q

NPY NEURONES in ARCUATE nucleus ACTIVATE NPY Y5 RECEPTORS in PVN to..

A

INCREASE FOOD INTAKE

(& INHIBIT MC4 & CART RECEPTORS)

39
Q

POMC CART NEUROTENSIN ACTIVATES MC4 (melanocortin 4) RECEPTOR / CART RECEPTOR to…

A

DECREASE FOOD INTAKE

(inhibitory mechanism)

40
Q

how does GLP-1 DECREASE FOOD INTAKE

A

INHIBITS NPY
ACTIVATES POMC CART

41
Q

how does LEPTIN DECREASE FOOD INTAKE

A

ACTIVATES POMC CART
- ACTIVATES MC4 & CART RECEPTORS

& INHIBITS NPY

42
Q

what does CLEAVAGE of POMC produce

A

MELANOCORTINS

43
Q

how do we get CLEAVAGE of POMC

A

by PROHOMONE CONVERTASES: PC1 & PC2

44
Q

what does targeted DELETION of MC4-R result in (in mice)

A

HYPERPHAGIA (excessive eating) & OBESITY

45
Q

ADIPOSE TISSUE is LOOSE CONNECTIVE TISSUE comprising of: (2)

A
  • ADIPOCYTES
  • STROMOVASCULAR CELLS

(and immune cells)

46
Q

ADIPOCYTES make up what proportion of our total cells

A

20-40%

majority is WHITE ADIPOSE CELLS

47
Q

STROMOVASCULAR COMPONENT of ADIPOSE TISSUE consists of:

A
  • ADIPOSE PRECURSORS
  • VASCULAR cells
  • IMMUNE cells
  • FIBROBLASTS
  • NERVE cells
48
Q

ADIPOCYTES are …. CELLS

A

LIPID-STORING cells

Safely STORE excess calories - overnutrition
- Free fatty acids (FFAs) and their products can be toxic when stored elsewhere

49
Q

ADIPOCYTES release..

A

energy-nutritional deprivation

  • RESERVE when levels are low
50
Q

what happens in ADIPOCYTES during POST-PRANDIAL PHASE (after eating)

A

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)

51
Q

what happens in ADIPOCYTES during FASTING (low insuline)

A

TAGs/TRIGLYCERIDES HYDROLYSED to FREE FATTY ACIDS and GLYCEROL

LIPASE activated

  • used as a source of ENERGY
52
Q

ADIPOSE TISSUE also acts as an…

A

ENDOCRINE ORGAN
secretes ADIPOKINES

53
Q

ADIPOKINES/HORMONES secreted by ADIPOSE TISSUE

A

IL-6
TNF ALPHA
- inflammatory mediators

PAI
- modifies blood coagulation

ANGIOTENSINOGEN
- regulates vascular tone

LEPTIN
- appetite regulation

ADIPONECTIN
- insulin sensitivity

54
Q

what is the main FUNCTION of LEPTIN

A

DECREASE FOOD INTAKE

55
Q

where is LEPTIN almost exclusively expressed

A

ADIPOSE TISSUE

56
Q

what is LEPTIN

A

SMALL POLYPEPTIDE
- 167 amino acids

57
Q

LEPTIN is encoded by which gene

A

LEP GENE
aka Ob gene

58
Q

effect of FATTY FOODS on LEPTIN

A

causes LEPTIN RELEASE
due to increased blood lipids

59
Q

another FUNCTION of LEPTIN

A

Regulates Activity of GONADAL and THYROID axis

60
Q

MUTATION in LEPTIN GENE (LEP) or LEPTIN RECEPTOR GENE results in

A

INTENSE HYPERPHAGIA (intense overeating) and consequently OBESITY

61
Q

what is ADIPONECTIN

A

highly secreted hormone from ADIPOSE TISSUE
- most ABUNDANT ADIPOKINE

62
Q

FUNCTION of ADIPONECTIN

A

ENHANCES INSULIN SENSITIVITY
in LIVER and PERIPHERAL tissue

63
Q

ADIPONECTIN acts via..
to enhance insulin sensitivity

A

ADIPOR1 & ADIPOR2 RECEPTORS

64
Q

what is the correlation between ADIPOSE TISSUE and ADIPONECTIN

A

HIGHER ADIPOSE TISSUE LEVELS
= LOWER ADIPONECTIN secretion

Paradoxically for an adipocyte-derived hormone, expression and secretion is diminished in central obesity

65
Q

ADIPONECTIN is an excellent biomarker for INSULIN RESISTANCE.
when there is LOW ADIPONECTIN…

A

HIGH INSULIN RESISTANCE

66
Q

ADIPONECTIN SECRETION is STIMULATED by…

A

THIAZOLIDINEDIONES (antidiabetic
agents)

67
Q

what are the 2 TYPES of ADIPOSE TISSUE

A

WHITE adipose tissue
BROWN adipose tissue

68
Q

ROLE of WHITE ADIPOSE TISSUE

A

STORES (excess) ENERGY as triglycerides

& SECRETES SIGNALLING FACTORS that regulate APPETITE & ENERGY HOMEOSTASIS
- leptin & adiponectin

69
Q

ROLE of BROWN ADIPOSE TISSUE

A

GENERATES BODY HEAT

  • helps SURVIVE COLD TEMPERATURES
    by transferring ENERGY FROM FOOD into HEAT
70
Q

CELLS in WHITE ADIPOSE TISSUE contain…

A

a SINGLE LARGE FAT DROPLET
- which forces the NUCLEUS to be SQUEEZED into a THIN RIM at the PERIPHERY

71
Q

WHITE ADIPOSE TISSUE responds to/ has RECEPTORS for…

A

INSULIN
SEX HORMONES
NORADRENALINE
GLUCOCORTICOIDS

72
Q

what does BROWN ADIPOSE TISSUE consist of

A

SMALL LIPID DROPLETS

numerous IRON-RICH MITOCHONDRIA (gives brown appearance)

73
Q

what gives BROWN ADIPOSE TISSUE its brown appearance

A

IRON-RICH MITOCHONDRIA

74
Q

where is BROWN ADIPOSE TISSUE (BAT) adundant

A

in SMALL MAMMALS and NEWBORNS

(some found in adults)

75
Q

OBESITY is associated with

A

INCREASE in ADIPOSE TISSUE MASS

76
Q

OBESITY occurs as a result of…

A

chronic IMBALANCE between ENERGY INTAKE and EXPENDITURE

involves interaction between GENETIC and ENVIRONMENTAL FACTORS

77
Q

GENETIC OBESITY CAUSES

A
  • 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
78
Q

EFFECTS of WEIGHT LOSS from Dieting

A
  • DECREASED LEPTIN
  • DECREASED PYY & GLP-1
  • INCREASED GHRELIN
    (feel hungry)
  • DECREASED ENERGY EXPENDITURE due to lower size

therefore hard to maintain weight loss

79
Q

Examples of treatments for obesity
- drugs that modify appetite control

A
  • LEPTIN TREATMENT
  • Setmelanotide drug - MC4R RECEPTOR for MC4R deficiency
  • Semaglutide - GLP1 AGONIST

(drugs that act on leptin pathway or melanocortin system)

80
Q

what is the action of Melanocortin Peptides eg (alpha-melanocyte-stimulating hormone) MSH released from ARC POMC NEURONS

A

BINDS to MELANOCORTIN RECEPTORS - MC4-Rs

to INHIBIT FOOD INTAKE

ENDOCRINOLOGY (11 decks)

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