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Physiology > Lecture 18: Endocrinology of Obesity > Flashcards

Lecture 18: Endocrinology of Obesity Flashcards

1
Q

What are a few common disorders associated with obesity

A

Orthopedic disorders, osteoarthritis, fractures, CCL’s, IVD, joint disorders, Cushing’s, DM, laryngeal paralysis, urolithiasism heat intolerance, exercise intolerance, reduced life span

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2
Q

What is the old view on the function of fat

A

Passive organ that is a depot for fat storage

Fat refers to lipids and cells/tissues that store lipids—> adipose tissue

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3
Q

What is the modern view on the functions of fat

A

Fat is a dynamic organ that does energy conversion and storage, influenced by hormones, releases hormones, regulates energy balance and nutritional homeostasis, generates heat with brown fat, cushions organs affects body shape and appearance

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4
Q

What is adiposity

A

How fat deposition occurs in the body

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5
Q

What are the three main fuel conversions

A
  1. Body proteins—> amino acids
  2. Glycogen storage—> glucose
  3. Triglycerides—> fatty acids
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6
Q

Obesity

A

Clinical state of excessive accumulation of body fat

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7
Q

Dyslipidemia or hyperlipidemia

A

Condition of abnormal lipid levels and/or their lipoproteins

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8
Q

How does dyslipidemia impact cholesterol, triglycerides, chylomucrons and low density lipoprotein levels

A

Elevates all

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9
Q

What are the two types of fat depots

A

White adipose tissue
Brown adipose tissue

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10
Q

What are the three types of adipocytes

A

White, brown beige

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11
Q

What are the two main cell types in WAT

A

Adipocytes ~50%
Pre-adipocytes ~2%

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12
Q

What type of fat generates heat

A

Brown fat

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13
Q

What hormones regulate brown fat

A
  1. Thyroid hormone- T3
  2. Epinephrine
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14
Q

How does thyroid hormone and epinephrine assist brown fat in heat production

A

Thyroid; T4–>T3 and then binds to THR-RXR in nucleus and promotes transcription of uncoupling protein 1 (UPC-1)

Epinephrine: binds G protein with second messenger signaling which converts triacylgycerol to FA

Both mechanisms result in heat production

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15
Q

What does UPC1 allow BAT to do

A

Directly transfer food energy into heat energy

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16
Q

Brown fat is predominately in what animals

A

Neonatal and hibernating

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17
Q

How can BAT activity be increased

A

Cold or epinephrine

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18
Q

How can beige fat in WAT be converted to BAT

A

T3, epinephrine, cold, hepatic bile acids, ANP/BNP, and Irisin

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19
Q

what is Hyperplasia in adipose tissue and when does it occur

A

Increase in number of adipocytes

Generally occurs during first year of life, late pregnancy, beginning of puberty, and during over- nutrition

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20
Q

Which is reversible and which is not in regards to expansion of adipose tissue: hypertrophy vs hyperplasia

A

Hypertrophy: reversible
Hyperplasia: irreversible

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21
Q

What hormone promotes storage of fats into adipocytes and stimulates an antilipolytic effect: FA-> TG

A

Insulin

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22
Q

What 3 things does insulin do in fuel conversion

A
  1. Stimulates lipoprotein lipase to convert TG to FA
  2. Stimulates GLUT4 to increase glucose uptake into adipocytes
    3., inhibits hormone sensitive lipase (blocks converting to FA)
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23
Q

What is insulins effect on lipids as fuel source

A

Decrease blood fatty acids, increase storage

Increases glucose uptake by adipocytes
Increase enzymes that produce FA
Increase fatty acid uptake
Decrease lipolysis

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24
Q

What hormones stimulate the lipolysis effect of TG-> FA

A

Epinephrine, cortisol, glucagon and growth hormone

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25
Q

What does epinephrine act on to trigger FA synthesis and release

A

Hormone sensitive lipase (HSL) and adipose tissue triglyceride lipase (ATGL)

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26
Q

How does thyroid hormone regulate fuel metabolites

A

No effect!

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27
Q

What are adipokines

A

Hormones of adipose organ

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28
Q

What are the two major adipokines

A

Leptin and adiponectin

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29
Q

What is the role of leptin

A

Metabolic regulator and feedback signal on appetite

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30
Q

What is the role of adiponectin

A

Insulin sensitizing and anti-inflammatory hormone

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31
Q

What is resistin

A

Released from macrophages, promotes insulin resistance and development of inflammation

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32
Q

What adipokine opposes adiponectin and is linked to type II DM and elevated LDL

A

Resistin

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33
Q

What is the role of omentin

A

Plays crucial role in the maintenance of body metabolism and insulin sensitivity. Has anti-inflammatory, anti-atherosclerotic, and cardiovascular protective effects

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34
Q

What is the role of visfatin

A

Released from visceral fat, binds the insulin receptor and exerts a hypoglycemic effect

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35
Q

What is the role of apelin

A

Decreases HR and increases BP; enhances brown adipogenesis of WAT. Upregulated by insulin and obesity

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36
Q

What type of macrophage increases pro-inflammatory cytokines

A

M1

37
Q

What inflammatory cytokines does M1 increases

A

TNF-alpha, IL-6, and IL-1

38
Q

What is TNF-alpha effect on insulin

A

Inhibits insulin

39
Q

Inflammation of fat results in insulin ____

A

Resistance

40
Q

Inflammation of fat causes increased levels of ___ released by macrophages

A

ROS

41
Q

Inflammation of fat is associated with an elevated risk of ___

A

Cancer

42
Q

Which proinflammatory cytokine promotes tumor growth

A

IL-1

43
Q

What does leptin do to appeteite

A

Binds to receptors in hypothalamus and suppresses appetite

44
Q

What is the mechanism in which leptin suppresses appetite

A

Stimulation of anorexigenic (appetite suppressing) neural pathways and suppression of orexigenic (appetite stimulating) neural pathways

Increases energy expenditure

45
Q

If leptin suppresses appetite why is it increased in obesity

A

Obese individuals become resistant to the actions of leptin

46
Q

What hormone stimulates adiponectin signaling

A

Insulin

47
Q

What are the beneficial effects of adiponectin signaling

A

Improves insulin sensitivity, anti-inflammatory, anti-athlerogenic

48
Q

What are the targets of adiponectin signaling

A
  1. Skeletal muscle to increase GLUT4
  2. Cardio protective effects- attenuates BP
  3. Stimulates liver to promote glucose uptake and energy storage
  4. Promotes adipogenesis and insulin directed glucose transport
49
Q

Adiponectin ___ is associated with obesity and insulin resistance

A

Deficiency

50
Q

Over expression of adiponectin can have negative effects and lead to what

A

Increase subcutaneous fat

51
Q

Obese dogs have more ___ and less ___

A

More leptin and less adiponectin

52
Q

Obese cats have less ___

A

Less adiponectin

53
Q

Where does leptin and insulin signaling take place in hypothalamus

A

Accurate nucleus

54
Q

What are the two opposing brain pathways in leptin and insulin signaling

A
  1. Melanocortins and cocaine and amphetamine regulated transcript
  2. Neuropeptide Y and agouti related protein
55
Q

What is the role of melanocortins (POMC) and cocaine amphetamine regulated transcript (CART)

A

Suppress appetite via activation of melanocortin 4 receptor (MC4R) and CRH: anorexigenic

56
Q

What is the role of neuropeptide Y (NPY) and agouti-related protein (AgRP)

A

Potent appetite stimulants for melanin concentrating hormone and orexin: orexigenic

57
Q

Where is Ghrelin released from and how does it impact NYP/AgRP and POMC/CART

A

Released from stomach and stimulates NYP/AgRP and inhibits POMC/CART

58
Q

Weight loss in obese individuals ___ leptin

A

Reduces

59
Q

Leptin stimulates what hormone in HPA axis

A

CRH

60
Q

What hormone inhibits neuropeptide Y cells

A

Insulin

61
Q

Which hormone slows gastric emptying and signals satiety

A

Amylin

62
Q

What does peptide PTT do

A

Released from small and large intestines and inhibits neuropeptide Y neurons

63
Q

What does cholecystokinin (CCK) do

A

Released from mucosal lining of small intestine in response to meal and signals satiety

64
Q

What does Glucagon like peptide 1 (GLP-1) do

A

Promotes insulin secretion and promotes appetite satiety

65
Q

An increase in CRH activates the HPA axis and ___ appetite

A

Inhibits

66
Q

What is the hunger hormone

A

Ghrelin

67
Q

Effect of leptin, insulin, PPY, and glucagon like peptide 1 on POMC/CART

A

Activates POMC/CART in arcuate nucleus signals to hypothalamus MCH1 and MCH14 to decrease appetite or feeding

68
Q

How does Ghrelin impact POMC/CART

A

Inhibits

69
Q

How does leptin, insulin, PPY, and glucagon like peptide affect NYP/AgRP

A

Inhibit

70
Q

What does ghrelin do to NPY/AgRP

A

Activates it to signal to hypothalamus to increase appetite

71
Q

High levels of leptin during obesity leads to ___ leptin signaling in hypothalamus

A

Decreased

72
Q

High leptin and decrease leptin signaling to hypothalamus results in what

A

Increased appetite

73
Q

What are plasma GH levels in obese individuals

A

Decreased

74
Q

What is thought to cause GH deficiency in obese animals

A

GHRH hyposecretion and somatostatin hypersecretion and hyperinsulinemia

75
Q

Leptin stimulates CRH and ACTH in HPA axis. What disease state would this resemble

A

Cushings

76
Q

How does obesity and leptin impact HPT axis

A

Exacerbate thyroid hormone resistance leading to hypothyroid state

77
Q

How does hypothyroidism caused by obesity and increase leptin affect basal metabolic rate

A

Decrease

78
Q

What type of tissue is a source and reservoir for sex steroids

A

Adipose

79
Q

What happens to free testosterone in male dogs due to obesity

A

Decrease free testosterone

80
Q

What happens to androgen levels in obese female dogs

A

Hyper androgen is leading to masculinization

81
Q

How does obesity affect pancreatic hormones

A

Results in insulin resistance and glucagon increased

82
Q

Insulin resistance is reversible with

A

Weight loss

83
Q

What causes hyperglucagonemia in obese animals

A

Insulin resistance in pancreatic alpha cells, promotes release of hepatic glucose and exacerbation of diabetes

84
Q

What happens to ghrelin levels during obesity

A

Decreases but bodies are more sensitive to ghrelin

Down regulated by high insulin and leptin

85
Q

GLP-1 affects on insulin and glucagon

A

Stimulates B cell insulin and inhibits glucagon

86
Q

GLP-1 levels in obesity

A

Reduced

87
Q

Peptide YY levels in obesity

A

Decreased

*similar to GLP-1

88
Q

How does fasting impact leptin levels

A

Decrease

89
Q

What is the correlation between leptin regained and weight

A

Increase leptin correlates to increase weight

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