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Obesity Medicine > Obesity Pathophysiology and Genetics > Flashcards

Obesity Pathophysiology and Genetics Flashcards

1
Q

Effects of the sympathetic nervous system on obesity

A

Increased brown fat thermogenesis

Increased adipose lipolysis

Increased spontaneous locomotor activity and myocardial activity

Increased muscle glycogenolysis, glucose, and fatty acid oxidation, and protein synthesis

Overall increased energy expenditure and decreased food intake

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2
Q

Is Serotonin orexigenic or anorexigenic

A

Anorexigenic, suppresses food intake

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3
Q

Where is POMC created

A

Arcuate Nucleus

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4
Q

Bardet-Biedl Syndrome is inherited via this type of inheritance

A

Autosomal recessive inheritance

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5
Q

Stress is particularly linked to this type of obesity

A

Visceral adiposity

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6
Q

The circadian rhythm is primarily regulated by this part of the brain

A

SCN Suprachiasmatic Nuclei (anterior hypothalamus)

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7
Q

Obesity is correlated with these changes in gut microbiota

A

Obesity causes a decrease in gut bacteroidetes and increased firmicutes

Bacteroidetes:Firmicutes ratio is low

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8
Q

Ghrelin is suppressed most by intake of this type macronutrient

A

Protein

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9
Q

This part of the brain is involved with impulse control and decision making

A

Prefrontal cortex

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10
Q

This type of obesity causes red hair, pale skin, hypopigmentation, low blood pressure, corticosteroid deficiency and adrenal insufficiency (low ACTH)

A

POMC Mutation

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11
Q

Which hormones are increased by Bariatric surgery

A 
Adiponectin
CCK
GLP-1
PYY
Glucagon
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12
Q

What type of obesity presents with developmental delay, short stature, short fingers, hypocalcemia, pseudohypoparathyroidism, precocious puberty, mild cognitive defects, and round facies

A

Albright Hereditary Osteodystrophy

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13
Q

What is CCK

A

Cholecystokinin

Short term satiation leading to meal termination

Slows gastric emptying

Stimulates pancreatic enzymes and bile

Opposes grehlin

Stimulated by fat and protein intake

Released by the I cells primarily in the duodenum

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14
Q

Is POMC orexigenic or anorexigenic

A

Anorexigenic, decreases food intake

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15
Q

What is Leptin?

A

An adipokine (created in fat) that acts in the hypothalamus (primarily Ventromedial hypothalmus)

Is increased in obesity/overfed –> General obesity is associated with Leptin resistance

However lack of Leptin leads to obesity also

Decreased appetite and increases energy expenditure.

Levels drops quickly when start to calorie restriction or have bariatric surgery

Along with Insulin, cross talks between homeostatic and hedonic system

Along with insulin activated the Sympathetic system (POMC/CART…)

Decreases as insulin decreases

Can be effected by poor quality sleep and fasting.

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16
Q

What activates AgRH/NPY

A

Ghrelin

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17
Q

Thiazolidinediones increase this obesity related hormone

A

Adiponectin

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18
Q

Hypoperfusion of the right frontal lobe leads to this change in weight

A

Overeating and Klein-Levin Syndrome

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19
Q

The prevalence of mono genetic obesity syndromes is higher in what area of the world

A

Eastern world (Pakistan, Turkey, Egypt, Austria …)

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20
Q

Gourmand Syndrome involves damage to this part of the brain

A

Right frontal lobe injury

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21
Q

Change in level of Leptin and Insulin in overfed state

A

Increased

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22
Q

GLP-1 is secreted by

A

I cells of the pancrease

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23
Q

What testing is done to eval for Bardet-Biedl Syndrome

A

Molecular testing for the BBS gene locus mutation

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24
Q

Glucagon is secreted from

A

alpha cells of pancreas

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25
Q

This type of obesity is caused by a maternal epigenetic methylation defect in adenylate cyclase-stimulating G alpha protein

A

Albright Hereditary Osteodystrophy

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26
Q

Melanin Concentrating Hormone is created here

A

Lateral Hypothalamus

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27
Q

Difference between hunger and appetite

A

Hunger is physical need for food

Appetite is a desire for food that can be emotional, sight/smell based etc

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28
Q

Change in level of GLP-1 after bariatric surgery

A

Increased

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29
Q

Where is serotonin created

A

Raphe nuclei in the brainstem

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30
Q

This part of the hypothalamus is the “satiety center”. Lesion in this area in mice causes obesity

A

Ventromedial hypothalamus (VMH)

Dense in Leptin receptors

Produces brain-derived neurotrophic factor (BDNF)

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31
Q

Does POMC/CART/MCR ultimately leads to activation of the sympathetic or parasympathetic system?

A

Sympathetic

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32
Q

Difference between probiotics and prebiotics

A

Prebiotics are non-digestible polysaccharides

Probiotics are live microorganisms

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33
Q

What is an adipokine? Most important examples

A

Cell signaling proteins/cytokines secreted by adipose tissue

Leptin
Adiponectin

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34
Q

Compared to lean individuals, in obese individuals Glucagon levels are

A

High

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35
Q

This part of the hypothalamus is the “hunger center”. Lesion in this area in mice causes anorexia

A

Lateral Hypothalamus (LH)

Creates melanin concentrating hormone (MCH)

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36
Q

What is adiponectin

A

An adipokine that is low in obesity and increases after bariatric surgery

Insulin sensitizing in the muscle. Anti-atherosclerosis effect. Increases fatty acid oxidation

Increased by TZDs

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37
Q

In mice models, when exposed to light at night what happens

A

Shift timing of food intake

Overall calorie intake doesn’t change, but does correlate with obesity

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38
Q

Change in Leptin and Insulin levels after bariatric surgery

A

Decreased

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39
Q

What type of obesity presents with hypotonia, blindness, polydactyly, hypogonadism, and retinitis pigmentosa

A

Bardet-Biedl Syndrome

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40
Q

Does AgRP/NPY ultimately leads to activation of the sympathetic or parasympathetic system?

A

Parasympathetic

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41
Q

What testing is done to eval for Prader Wili

A

DNA Methylation analysis

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42
Q

What is correlated with increased brown fat thermogenesis

A 
Cold
Thermic effect of food
Women have more then men
Young have more than old
Lean have more than obese

Especially high in newborns and hibernating animals

Sympathetic nervous system innervation

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43
Q

The most common known genetic cause of obesity

A

Melanocortin 4 Receptor Deficiency

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44
Q

The only circulating orexigen is

A

Ghrelin

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45
Q

Which hormones are high in obesity

A

Leptin
Insulin
Glucagon

Ghrelin high in PWS. Unclear if high in general obesity

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46
Q

Change in level of Amylin in overfed state

A

Increased

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47
Q

Site of action of insulin

A

Hypothalamus

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48
Q

Effects of Alpha Melanocyte Stimulating Hormone on appetite

A

Decreased

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49
Q

What parts of the brain are involved with the Hedonic Pathway

A

Ventral Tegmental Area
Nucleus Accumbens
Frontal Accumbens

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50
Q

Which hormones are decreased by Bariatric surgery

A

Leptin
Ghrelin
Insulin

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51
Q

How is stress linked to obesity

A

Like transient diabetes

Stress —> Cortisol —> insulin resistance —> Leptin resistance

52
Q

Dementia with degeneration of the right frontal lobe leads to this change in weight

A

Hyperphagia and weight gain

53
Q

What inhibits AgRH/NPY

A

POMC

54
Q

This type of obesity presents with tall stature, normal mental status, increased lean muscle mass and hyperphagia

A

Heterozygous MC4R frameshift mutation

55
Q

Compared to lean individuals, in obese individuals Leptin and Insulin levels are

A

High

56
Q

Leptin is created here

A

White fat

57
Q

This type of syndromic obesity can be very successfully treated

A

Leptin deficiency, treat with Leptin

There is a new drug Setmelanotide that shows promise in POMC deficiency

58
Q

Change in level of CCK after bariatric surgery

A

Increased

59
Q

What activates Cocaine and Amphetamine Regulation Transcript (CART)

A

Insulin and Leptin

60
Q

Which hormones are decreased in an over fed state and increased in an underfed state

A

Ghrelin

61
Q

CCK is secreted from

A

I cells in the duodenum

62
Q

This type of genetic obesity has increased Ghrelin

A

Prader Willi Syndrome

63
Q

Change in level of Adiponecton after bariatric surgery

A

Increased

64
Q

This type of obesity is caused by a autosomal recessive defect in cilia

A

Bardet-Biedl Syndrome

65
Q

Does Insulin ultimately leads to activation of the sympathetic or parasympathetic system?

A

Sympathetic

66
Q

What is PYY

A

Increases satiety and stimulates glucose mediated insulin secretion.

Degraded by DPP-4

Secreted by intestinal I cell (most in the ileum/colon)

Experimental drug combo used for obesity

67
Q

This system in the nervous system is implicated in desire for food palatability and reward seeking behavior

A

Hedonic System

68
Q

Prader Wili has what changes in Leptin and Grehlin

A

Increased ghrelin

Leptin increased, but at similar level to non-syndrome obese

69
Q

Change in level of Ghrelin in overfed state

A

Decreased

70
Q

Compared to lean individuals, in obese individuals GLP-1 levels are

A

Low

71
Q

What 2 substances are secreted by the pancrease to decrease hunger and increase satiety

A

Amylin

Insulin

72
Q

What is an Orexigen

A

Hormone or substance that stimulates appetite

73
Q

What activates POMC

A

Leptin
Insulin

Through LepR

74
Q

Change in level of Glucagon in overfed state

A

Increased

75
Q

How does the activity of the dorsolateral prefrontal cortex in obese patients compare to lean patients

A

Decreased activation potentially causing less impulse control

Remains low even after weight loss

Is increased in obese children and is linked to low self esteem

76
Q

This obesity condition includes short stature, hypotonia and developmental delay as well as narrow temple distance, narrow nasal bridge, almond shaped eyes, mild strabismus, and downturned upper lip

A

Prader Willi

77
Q

Change in level of PYY in overfed state

A

Increased

78
Q

Appetite from the hedonic system is highest when _ is low

A

Insulin and Leptin

79
Q

Which type of adipose tissue is more dangerous

A

Visceral adipose (in liver, pericardium, muscle etc)

Subcutaneous fat is much less dangerous

80
Q

This part of the brain creates brain-derived neurotrophic factor (BDNF) which is involved in hedonic and homeostatic energy regulation and if decreased can contribute to obesity

A

Ventromedial hypothalamus

81
Q

What inhibits POMC

A

AgRH

NPY

82
Q

What is Ghrelin

A

Growth Hormone Release Inducing Peptide

Hunger hormone, peaks before meals

Secreted by the fundas

Suppressed the most by protein intake

Increased in Prader Wili

Increase when calorie restrict

83
Q

What is GLP-1

A

Secreted by I cells in the intestine (the most in ileum/colon)

Degraded by DPP-4

Increases beta cell insulin release, delays gastric motility/secretions, delays carb absorption, and increases satiety (by inhibiting orexigenic NPY)

84
Q

What type of obesity presents with altered immune system, delayed puberty, and hyperphagia

A

Congenital Leptin Deficiency

Congenital Leptin Receptor Deficiency

85
Q

This neurotransmitter stimulates MCR4 and inhibits AgRP/NPY

A

Proopiomelanocortin (POMC)

86
Q

This type of obesity has very high levels of Leptin

A

Leptin receptor deficiency

87
Q

Change in level of GLP-1 in overfed state

A

Increased

88
Q

Is Agouti Related Peptide (AgRP) orexigenic or anorexigenic

A

Orexigenic, increases food intake

89
Q

Where is AgRP created

A

Arcuate Nucleus

90
Q

What 3 substances are secreted by the intestine to act peripherally decreasing hunger and increase satiety

A

CCK
GLP-1
PYY

91
Q

This general picture should raise concern for genetic obesity

A

Normal birth weight followed by rapid severe onset of obesity with impaired satiety, hyperphasia, and constant food seeking behavior

92
Q

This virus has been linked to an infectious type of obesity

A

Adenovirus 36

30% in obese humans and 11% in thin

Presence of antibodies among population has been increasing

Induced obesity in animal models

Thought to induce stem cell differentiation into preadipocytes via PPAR gamma signaling

93
Q

These hormones from the homeostatic system augment the affects of the hedonic system

A

Insulin/Leptin cross talk to hedonic dopamine system by affecting dopamine’s reuptake and clearance from the synapse

94
Q

Is Neuropeptide Y (NPY) orexigenic or anorexigenic

A

Orexigenic, increases food intake

95
Q

Concentration of Dopamine receptors in the brain of obese people compared to lean

A

Less

Unsure if cause or affect

96
Q

This is the signature protein in brown adipose tissue thermogenesis

A

Uncoupling protein 1 (UCP1) which uncoupled oxidative phosphorylation in mitochondria generating heat

97
Q

Patient with frontal lobotomy’s have this effect on weight

A

Overeating and obesity

98
Q

Change in level of PYY after bariatric surgery

A

Increased

99
Q

Which hormones are low in obesity

A

Adiponectin
CCK
GLP-1
PYY

100
Q

What neurotransmitters does the Arcuate nucleus create

A

POMC
NPY
AgRP

101
Q

Compared to lean individuals, in obese individuals Adiponecton levels are

A

Low

102
Q

Leptin acts here

A

Hypothalamus (Ventromedial hypothalmus)

103
Q

PYY is secreted from

A

I cells in the duodenum

104
Q

Change in level of CCK in overfed state

A

Increased

105
Q

This part of the brain is most closely associated with Norepinephrine production

A

Locus Coeruleus

106
Q

Which hormones are increased in an over fed state and decreased in an underfed state

A 
Leptin
CCK
GLP-1
PYY
Amylin
Insulin
Glucagon
107
Q

What is Leptin?

A

An adipokine (created in fat) that acts in the hypothalamus (primarily Ventromedial hypothalmus)

Is increased in obesity/overfed –> General obesity is associated with Leptin resistance

However lack of Leptin leads to obesity also

Increases appetite and decreases energy expenditure.

Levels drops quickly when start to calorie restriction or have bariatric surgery

Along with Insulin, cross talks between homeostatic and hedonic system

Along with insulin activated the Sympathetic system (POMC/CART…)

Decreases as insulin decreases

Can be effected by poor quality sleep and fasting.

108
Q

Changes in adiponectin are associated with what health conditions (independent of obesity)

A

Low in T2DM, NASH, atherosclerosis, MI, and CHF

High in osteoarthritis

109
Q

This adipokine is increased in obese and leads to atherosclerosis and insulin resistance

A

Resistin

110
Q

Effect of insulin on appetite

A

Decreases food intake

111
Q

Compared to lean individuals, in obese individuals PYY levels are

A

Low

112
Q

This is the “anti-Ghrelin” which leads to short term satiation and meal termination

A

CCK

113
Q

What is Amylin

A

Decreases food intake, inhibits gastric emptying, inhibits gastric acid secretion, enhances CCK, and effects bone metabolism

Consecreted with insulin by pancreatic beta cells

Symlin/Pramlintide is a diabetic drug being studied for possible use in combo weight loss medications

114
Q

Where is NPY created

A

Arcuate Nucleus

115
Q

Compared to lean individuals, in obese individuals CCK levels are

A

Low

116
Q

This type of obesity is caused by a epigenetic 15q partial deletion on paternal chromosome

A

Prader Willi

117
Q

Anorexigens

A

Hormone or substance which inhibits hunger and promotes satiety

118
Q

This type of obesity has very low levels of Leptin

A

Leptin deficiency

119
Q

Most abundant adipokine

A

Adiponectin

120
Q

Does Grehlin ultimately leads to activation of the sympathetic or parasympathetic system?

A

Parasympathetic

121
Q

When bacteria free mice are given a microbiota transfer of obese vs lean donor, what happens

A

Mouse adopts phenotype of donor

122
Q

Klein-Levin Syndrome is caused by this

A

Hypoperfusion of the right frontal lobe

123
Q

Hyperactivity of the right prefrontal cortex leads to this change in weight

A

Anorexia and weight loss

124
Q

The primary neurotransmitter of the Hedonic Pathway is

A

Dopamine

125
Q

Ghrelin is secreted by

A

Fundas of the stomach

126
Q

Does Leptin ultimately lead to activation of the sympathetic or parasympathetic system

A

Sympathetic

Obesity Medicine (5 decks)

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