Endo 2:1 Komar Adipose Tissue

Front 1

What are the 6 organ systems affected by adipocyte-derved factors?

Back 1

1. vasculature
2. muscle
3. brain
4. repro
5. beta cells
6. liver

Front 2

What are the stages of adipogenesis? 4

Back 2

1. Mesenchymal cells ungergo proliferation and determination becoming
2. Preadipocytes that undergo proliferation and differentiation into
3. Immature multiocular adipocytes that hypertrophy into
4. mature unilocular adipocytes

Front 3

From a mesenchymal stem cell what are the 3 options of what they could turn into? and what 3 things determine that?

Back 3

1. osteocyte, adipocyte, and myocyte
2. gene expression, timing, and balance

Front 4

What is the receptor that activates mesenchymal stem cells into adipocytes?

Back 4

Perozone Proliferator Activated receptor. PPAR

Front 5

What are the 2 phases that adipogenesis is divided into?

Back 5

1. determination - involves the commitment of a pluripotent stem cell to the adipocyte lineage
2. as terminal differentiation, the preadipocyte takes on the characteristics of the mature adipocyte

Front 6

What does the determination phase of adipogenesis result in?

Back 6

This results in the conversion of the stem cell to a preadipocyte, which cannot be distinguished morphologically from its precursor cell but has lost the potential to differentiate into other cell types

Front 7

What are the characteristics of a mature adipocyte?

Back 7

1. lipid transport and synthesis
2. insulin sensitivity
3. the secretion of adipocyte-specific proteins

Front 8

What are adipokines?

Back 8

- proteins produced by adipose tissue that have autocrine, paracrine, and /or endocrine effects
- some are unique to adipose tissue and others are not

Front 9

What are the adipokines of the adipose tissue involved in the immune system? 3

Back 9

TNF alpha, IL-6, C-reactive protein

Front 10

What are the adipokines of the adipose tissue involved in growth factors? 2

Back 10

TGF - beta and IGF - 1

Front 11

What are the adipokines of the adipose tissue involved in the complement pathway? 1

Back 11

adipsin

Front 12

What are the adipokines of the adipose tissue involved in the appetite and metabolism? 3

Back 12

1. leptin
2. adiponectin
3. resistin

Front 13

What are the adipokines of the adipose tissue involved in the vascular system? 3

Back 13

1. VEGF
2. RAS
3. PAI -1

Front 14

What are the adipokines of the adipose tissue involved with steroids? 2

Back 14

1. glucocorticoids
2. estradiols

Front 15

What is Leptin? What determines how much is secreted?

Back 15

1. a polypeptide hormone similar to cytokines with long and short receptors that reside in the CNS and peripheral tissues
2. It is secreted in direct proportion to the amount of adipose tissue

Front 16

When is Leptin secretion increased? 4

Back 16

1. insulin
2. glucocorticoids
3. TNF-alpha
4. estrogen

Front 17

When is Leptin secretion decreased? 4

Back 17

1. Beta3-adrenergic
2. androgens
3. Free Fatty acids
4. Growth hormone

Front 18

What is the effect of Leptin?

Back 18

energy intake and expenditure -> satiety factor.

Front 19

What mediates the effect of Leptin?

Back 19

Hypothalamic pathways
- increased by POMC
- decreased by NPY

Front 20

What happens to Leptin in obese pts?

Back 20

elevated in obesity and develops resistance, dec the signaling and is no longer effective as a satiety factor

Front 21

What peripheral tissues does Leptin effect? 4

Back 21

1. ovary, prostate, testis, placenta
2. immune factors
3. hematopoiesis
4. bone development

Front 22

What increases Leptin satiety factor? 3

Back 22

1. POMC
2. Glucose uptake by skeletal muscle
3. TRH expression and secretion from hypothalamus: important for secretion in puberty

Front 23

What dec the effect of Leptin in satiety factor? 2

Back 23

1. NPY neurons
2. insulin secretion and synthesis of pre-proinsulin

Front 24

What kind of relationship does adiponectin have with insulin resistance and inflammatory states?

Back 24

It has an inverse relationship. The more adiponectin there s the less insulin resistance and inflammatory states there will be.

Front 25

What are the effects of Adiponectin in the liver? 3

Back 25

1. inc insulin sensitivity
2. dec hepatic glucose output
3. inc Fatty acid oxidation

Front 26

What are the effects of adiponectin in the muscles? 2

Back 26

1. inc. glucose use
2. inc fatty acid oxidation

Front 27

What are the uses of adiponectin in the vascular wall? 4

Back 27

1. dec adhesion molecule expression
2. dec monocyte adhesion
3. dec macrophage transformation into foam cells
4. dec VSMC proliferation

Front 28

What are the 3 effects of Resistin?

Back 28

1. resistance to insulin
2. dec glucose uptake by the liver
3. proinflammatory

Front 29

How is IL-6 implicated in the pathogenesis of obesity and insulin resistance?

Back 29

1. dec secretion of adiponectin
2. dec expression of insulin receptor signaling

Front 30

How does skeletal muscle IL-6 differ from adipose IL-6?

Back 30

In the skeletal m. IL-6 increases glucose uptake and dec inflammation. In adipose and hepatic, IL-6 s proinflammatory and impairs insulin induced IR and IRS1 phorylation thus inhibiting insulin.

Front 31

What does Caspase-1 do?

Back 31

activates IL-1beta and IL-18 causing the inflammatory state associated with obesty

Front 32

What is TNFalpha implicated with? 4

Back 32

1. pathogenesis of obesity and insulin resistance
2. inc in obesity
3. dec uptake and storage of NEFA and glucose
4. dec insulin signaling via degradation of IRS 1 and 2

Front 33

What does PAI-1 inhibit?

Back 33

uPA and tPA

Front 34

What is PAI-1 (Plasminogen Activator Inhibitor -1 correlated with?

Back 34

1. inc in obesity and insulin resistance may lead to DM II and CVD
2. may promote neointimal growth by dec fibrinolysis thereby stabilizing fibrin matrix for VSMS migration and promting VSMC proliferation

Front 35

How are adipose tissue marcophages (ATMs) connected with CVD and DM?

Back 35

In obese ppl, they lose the ability to store triglycerides well and allow them into circulation. Then, FFAs trigger ATMs to produce proinflamatory cytokines, such as TNF-alpha and PAI-1. These can lead to insulin resistance, which sustains FFA release and feed-forward mechanisms. PAI- causes ectopic fats deposits that inc the risk for thrombi.

Front 36

What are the changes in adipose tissue, liver, and muscle with obesity and insulin resistance?

Back 36

1. Lean subjects = few macrophages, high adiponectin, and low inflammatory cytokines. β-Oxidation of lipids in muscle is high, and little ectopic fat in the muscle and liver.
2. Obesity and insulin resistance = many macrophages, high adipokines, and low levels of adiponectin. This adipose tissue may be limited in its lipid storage capacity, and this feature, along with the pro-inflammatory state, promotes ectopic lipid accumulation

Front 37

What is the link between the FFA and the Toll Like Receptor 4 pathway?

Back 37

FetA, FFAs and LPS can both stimulate Tlr4 signaling; LPS directly binds the Tlr4-CD14 complex, whereas FFAs bind FetA, which then binds Tlr4. TLR4 signaling leads to the activation of the transcription factors nuclear factor-κB (NF-κB) and AP-1, which can then upregulate the transcription of inflammatory genes, resulting in the production of inflammatory cytokines that can lead to insulin resistance.

Front 38

Which is worse: viceral or subcutaneous fat?

Back 38

increased visceral adipose tissue is associated with an increased risk of insulin resistance and cardiovascular disease, whereas increased subcutaneous adipose tissue is not

Front 39

What is the role of 11betaHSD1?

Back 39

the role of 11betaHSD1 is to convert inactive cortisone into active cortisol and glucocorticoids (+) adipocyte formation

Front 40

What are the main things visceral adipose produces? 7

Back 40

1. IL-6
2. PAI-1
3. Resistin
4. Angiotensinogen
5. ACE
6. 11betaHSD1
7. capase-1

Front 41

What are the main things subcutaneous adipose produces? 3

Back 41

1. leptin
2. TNF-alpha
3. adiponectin

Front 42

What suppresses appetite? 7

Back 42

1. POMC - proopiomelanocortin
2. CART - cocaine and amphetamine regulated transcript
2. Leptin
3. Insulin
4. PYY -peptide YY
5. GLP1 - glucagon‐like peptide 1
6. Oxm - oxyntomodulin
7. PP - pancreatic polypeptide

Front 43

What increase appetite?

Back 43

1. NPY - neuropeptide Y
2. AgRP - agouti related peptide
3. Ghrelin
4. MCH - , melanin concentrating hormone;
5. Orexins

Front 44

Draw the appetite control schematic.

Back 44

Front 45

What provides the stimulation of feeding?

Back 45

Neuropeptide Y pathway

Front 46

What peptide elicits satiety?

Back 46

Cholecystokinin (CCK) released from I cells in the duodenal mucosa in repsonse to fat and protein digestion. It inhibits gastric empying resulting in distention and contributes to the satiety response.

Front 47

What is the source? site of action? and clinical effects of insulin?

Back 47

1. beta cells
2. Hypothalamus
3. dec appetite, inc metabolism

Front 48

What is the source? site of action? and clinical effects of leptin?

Back 48

1. adipocytes
2. hypothalams
3. dec app, inc metabolism

Front 49

What is the source? site of action? and clinical effects of CCK (Cholecystokinin) ?

Back 49

1. I cells of the duodenum
2. vagal afferents
3. dec appeitie, dec gastric emptying

Front 50

What is the source? site of action? and clinical effects of PYY?

Back 50

1. L cells of the ileum, cecum, colon
2. hypo and vagus
3. dec appetite, inc meta, dec gastric emptying

Front 51

What is the source? site of action? and clinical effects of ghrelin?

Back 51

1. endocrine cells of gastric fundus
2. hypo
3. inc appetite, dec metabolism

Front 52

What is the source? site of action? and clinical effects of PP?

Back 52

1. pancreatic islet PP cells
2. Hypo
3. dec appetite

Front 53

What is the source? site of action? and clinical effects of amylin?

Back 53

1. pancreatic islet PP cells
2. hypo
3. dec gastric empying, dec glucagon, dec appetite

Front 54

What is the source? site of action? and clinical effects of GLP-1?

Back 54

1. L cells
2. Brainstem and Pancreas
3. inc insulin release, dec glucagon, dec gastric emptying, dec appetite

Front 55

What is the source and clinical effects of GIP?

Back 55

1. K cells
2. inc insulin release and dec glucagon

Front 56

What is the source? site of action? and clinical effects of Glucagon?

Back 56

1. pancreatic alpha cells
2. liver
3. inc hepatic glycogenolysis and gluconeogenesis

Front 57

What is the source and clinical effects of oxyntomodulin?

Back 57

1. L cells
2. dec appetite and dec gastric emptying

Front 58

What is metabolic syndrome or syndrome X? 5

Back 58

Complex interrelated rsk factors for developing CVD and DM.
1. High BP
2. Elevated blood glucose
3. high triglycerides
4. low levels of HDL
5. central adipocity

Front 59

What are the clinical criteria for metabolic syndrome? 5

Back 59

waist circumference: ♂ >102 cm (40 in); ♀ >88 cm (35 in)
triglycerides > 150 mg/dL
HDL cholesterol <40 mg/dL ♂; <50 mg/dL ♀
blood pressure > 130 / 85 mmHg
fasting glucose >100 mg/dl

Front 60

tx for obesity, metabolic syndrome, or type 2 DM?

Back 60

1. lifestyle changes
2. pharm
3. surgery -> baratric

Front 61

What are the pharm interventions for obesity, DM, and metabolic syndrome? 3

Back 61

1. Orlistat (Xenical) - dec gastric and pancreatic lipases, ↓ absorption of undigested triglycerides
2. Lorcaserin (Belviq) - selective agonist of 5-HT2C receptor (satiety factor that can affect metabolism)
3. Phentermine + extended release topiramate (Qsymia) - reduce appetite and may increase metabolism (can cause birth defects: restricted use in US)

Front 62

What are some targets for antiobesity drugs? 3

Back 62

1. leptin
2. cholecystokinin
3. glucagon-like peptide = dec glucagon secretion and inc pancreatic beta cells
4. dipeptidyl peptidase 4 inhibitors - catabolzes GLP-1
5. peptide YY - anorexigenic and dec meal size
6. amylin - limits meal size
7. ghrelin - dec insulin secretion

Front 63

Mechanism behind success of surgery? 3

Back 63

1. Increased secretion of peptide YY and amylin
Amylin can synergize with leptin and peptide YY to increase satiety
thereby ↓ food intake
2. Removal of stomach – less ghrelin which is orexigenic primarily secreted from fundus

3. Interposition of ileum – early exposure of ingested food → GLP-1 secretion from L cells:
slows gastric emptying
(-) apoptosis of pancreatic β cells
(+) growth and differentiation of pancreatic β cells
plays a role in satiety