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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
What does epinephrine act on to trigger FA synthesis and release
Hormone sensitive lipase (HSL) and adipose tissue triglyceride lipase (ATGL)
26
How does thyroid hormone regulate fuel metabolites
No effect!
27
What are adipokines
Hormones of adipose organ
28
What are the two major adipokines
Leptin and adiponectin
29
What is the role of leptin
Metabolic regulator and feedback signal on appetite
30
What is the role of adiponectin
Insulin sensitizing and anti-inflammatory hormone
31
What is resistin
Released from macrophages, promotes insulin resistance and development of inflammation
32
What adipokine opposes adiponectin and is linked to type II DM and elevated LDL
Resistin
33
What is the role of omentin
Plays crucial role in the maintenance of body metabolism and insulin sensitivity. Has anti-inflammatory, anti-atherosclerotic, and cardiovascular protective effects
34
What is the role of visfatin
Released from visceral fat, binds the insulin receptor and exerts a hypoglycemic effect
35
What is the role of apelin
Decreases HR and increases BP; enhances brown adipogenesis of WAT. Upregulated by insulin and obesity
36
What type of macrophage increases pro-inflammatory cytokines
M1
37
What inflammatory cytokines does M1 increases
TNF-alpha, IL-6, and IL-1
38
What is TNF-alpha effect on insulin
Inhibits insulin
39
Inflammation of fat results in insulin ____
Resistance
40
Inflammation of fat causes increased levels of ___ released by macrophages
ROS
41
Inflammation of fat is associated with an elevated risk of ___
Cancer
42
Which proinflammatory cytokine promotes tumor growth
IL-1
43
What does leptin do to appeteite
Binds to receptors in hypothalamus and suppresses appetite
44
What is the mechanism in which leptin suppresses appetite
Stimulation of anorexigenic (appetite suppressing) neural pathways and suppression of orexigenic (appetite stimulating) neural pathways Increases energy expenditure
45
If leptin suppresses appetite why is it increased in obesity
Obese individuals become resistant to the actions of leptin
46
What hormone stimulates adiponectin signaling
Insulin
47
What are the beneficial effects of adiponectin signaling
Improves insulin sensitivity, anti-inflammatory, anti-athlerogenic
48
What are the targets of adiponectin signaling
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
Adiponectin ___ is associated with obesity and insulin resistance
Deficiency
50
Over expression of adiponectin can have negative effects and lead to what
Increase subcutaneous fat
51
Obese dogs have more ___ and less ___
More leptin and less adiponectin
52
Obese cats have less ___
Less adiponectin
53
Where does leptin and insulin signaling take place in hypothalamus
Accurate nucleus
54
What are the two opposing brain pathways in leptin and insulin signaling
1. Melanocortins and cocaine and amphetamine regulated transcript 2. Neuropeptide Y and agouti related protein
55
What is the role of melanocortins (POMC) and cocaine amphetamine regulated transcript (CART)
Suppress appetite via activation of melanocortin 4 receptor (MC4R) and CRH: anorexigenic
56
What is the role of neuropeptide Y (NPY) and agouti-related protein (AgRP)
Potent appetite stimulants for melanin concentrating hormone and orexin: orexigenic
57
Where is Ghrelin released from and how does it impact NYP/AgRP and POMC/CART
Released from stomach and stimulates NYP/AgRP and inhibits POMC/CART
58
Weight loss in obese individuals ___ leptin
Reduces
59
Leptin stimulates what hormone in HPA axis
CRH
60
What hormone inhibits neuropeptide Y cells
Insulin
61
Which hormone slows gastric emptying and signals satiety
Amylin
62
What does peptide PTT do
Released from small and large intestines and inhibits neuropeptide Y neurons
63
What does cholecystokinin (CCK) do
Released from mucosal lining of small intestine in response to meal and signals satiety
64
What does Glucagon like peptide 1 (GLP-1) do
Promotes insulin secretion and promotes appetite satiety
65
An increase in CRH activates the HPA axis and ___ appetite
Inhibits
66
What is the hunger hormone
Ghrelin
67
Effect of leptin, insulin, PPY, and glucagon like peptide 1 on POMC/CART
Activates POMC/CART in arcuate nucleus signals to hypothalamus MCH1 and MCH14 to decrease appetite or feeding
68
How does Ghrelin impact POMC/CART
Inhibits
69
How does leptin, insulin, PPY, and glucagon like peptide affect NYP/AgRP
Inhibit
70
What does ghrelin do to NPY/AgRP
Activates it to signal to hypothalamus to increase appetite
71
High levels of leptin during obesity leads to ___ leptin signaling in hypothalamus
Decreased
72
High leptin and decrease leptin signaling to hypothalamus results in what
Increased appetite
73
What are plasma GH levels in obese individuals
Decreased
74
What is thought to cause GH deficiency in obese animals
GHRH hyposecretion and somatostatin hypersecretion and hyperinsulinemia
75
Leptin stimulates CRH and ACTH in HPA axis. What disease state would this resemble
Cushings
76
How does obesity and leptin impact HPT axis
Exacerbate thyroid hormone resistance leading to hypothyroid state
77
How does hypothyroidism caused by obesity and increase leptin affect basal metabolic rate
Decrease
78
What type of tissue is a source and reservoir for sex steroids
Adipose
79
What happens to free testosterone in male dogs due to obesity
Decrease free testosterone
80
What happens to androgen levels in obese female dogs
Hyper androgen is leading to masculinization
81
How does obesity affect pancreatic hormones
Results in insulin resistance and glucagon increased
82
Insulin resistance is reversible with
Weight loss
83
What causes hyperglucagonemia in obese animals
Insulin resistance in pancreatic alpha cells, promotes release of hepatic glucose and exacerbation of diabetes
84
What happens to ghrelin levels during obesity
Decreases but bodies are more sensitive to ghrelin Down regulated by high insulin and leptin
85
GLP-1 affects on insulin and glucagon
Stimulates B cell insulin and inhibits glucagon
86
GLP-1 levels in obesity
Reduced
87
Peptide YY levels in obesity
Decreased *similar to GLP-1
88
How does fasting impact leptin levels
Decrease
89
What is the correlation between leptin regained and weight
Increase leptin correlates to increase weight

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