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obesity Flashcards

go through this lec again maybe even extra reading bc dam

1
Q

what is obesity

A

Abnormal and/or excessive fat accumulation with systemic low-grade
inflammation to create a health risk

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2
Q

is obesity considered an inflammatory disease and why/why not

A

yes as inflammatory diseases effect beyond adipose tissues into the circulation and other tissues e.g. liver

obesity disturbs a wide range of inflammatory cascades leading to infection complications and inc risk of vaccine failure

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3
Q

what are monocytes

A

make up 5-10% of circulating leukocytes

several roles including phagocytosis, antigen presentation and cytokine production

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4
Q

what can monocytes differentiate into

A

macrophages

typically M1-like macrophages or M2-like macrophages

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5
Q

what are M1-like macrophage functions - 3

A

pro inflammatory
microbicidal
tumoricidal

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6
Q

M2-like macrophages functions - 4

A

anti inflammatory
phagocytosis
angiogenesis
tissue repair

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7
Q

how many people does obesity affect

A

1/4 adults and 1/5 children aged 10-11 in uk

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8
Q

what is an indicator of obesity

A

BMI (weight and height)

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9
Q

BMI, what is considered a healthy weight

A

<25

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10
Q

BMI, what is considered overweight

A

25-30

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11
Q

BMI, what is considered obese

A

30-40

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12
Q

BMI, what is considered morbidly obese

A

> 40

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13
Q

causes of obesity - 2

A

consuming more calories than u burn off

underlying health conditions like hypothyroidism

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14
Q

treatments of obesity - 4

A

eat healthy reduced calorie diet, exercise regularly

recieve psychological support

medication like orlistat

weight loss surgery

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15
Q

problems related to obesity/ symptoms - 6

A

depression

psychological problems

breathlessness

joint and back pain

increased sweating

fatigue

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16
Q

what is white adipose tissue WAT

A

white fat

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17
Q

what is the healthy WAT amount of body fat in men

A

20%

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18
Q

what is the healthy amount of WAT of body fat in females

A

25%

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19
Q

how much of WAT is adipocytes

A

1/3

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20
Q

what does WAT include - 4

A

adipocytes

fibroblasts

leukocytes

endothelial cells

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21
Q

examples of where WAT is found

A

subcutaenous layer under skin

buttocks

thighs

abdominal cavity

around organs

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22
Q

what does adipose tissue act as

A

endocrine system - generates hormones that influence metabolic activity e.g. inc insulin sensitivity to protect against obesity

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23
Q

what state do adipocytes exist in

A

semi liquid state

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24
Q

what are adipocytes primarily composed of - 2

A

triglycerides

cholesteryl esters

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25
adipocytes and excess weight
adipocytes inc size by 4x before dividing to increase number
26
how are adipocytes produced
adipogensis
27
describe adipogenesis process in obesity
mesenchymal stem cell pre-adipocyte adipocyte undergoes hypertrophy (and to a lesser extent hyperplasia/proliferation) wham adipocyte
28
what does insulin promote in the context of obesity and what is result
free fatty acid uptake into adipocytes by stimulating LPL mediated release of free fatty acids from lipid proteins free fatty acids enter cell through passive diffusion or fatty acid transporters insulin then stimulates glucose transport into adipocyte by inc avaliability of glycerol-3-phosphate for triglyceride synthesis produces triglyceride storage
29
fatty acid transporter example
CD36
30
where is insulin produced
by beta cells of pancreatic islets
31
what does insulin do
regulates metabolism of carbohydrates, fats and protein
32
when is insulin released
in response to high blood glucose
33
what is ghrelin
hunger hormone
34
what is ghrelin released by
stomach and upper intestine
35
what is leptin
satiety hormone
36
what is leptin produced by
adipose tissue indirectly or in an autocrine action
37
what does leptin stimulate - 2
fatty acid oxidation pro inflammatory response
38
hunger response - adipose, leptin, response
adipose cells empty no leptin signal to hypothalamus munch
39
satiety response - adipose, leptin, response
adipose cells full leptin signal sent to hypothalamus no munch
40
leptin resistance occurs how - 2
excess eating, higher levels of leptin produced, body becomes desensitised, causes overeating as dont know when full also inc with age
41
leukocytes express OB-R (LEPR/CD295). what is this
receptor for leptin
42
what does activation of OB-R (LEPR/CD295) cause
activation of innate immune cells - monocytes, neutrophils, MK cells downregulates apoptosis upregulates proliferation (including of adaptive immune cells), enhances function: cytotoxicity of MK cells phagocytosis of monocytes cytokine release of granulocytes overall, pro inflammatory response
43
what does leptin inhibit production of
anti viral type 1 interferons against viruses
44
what type of environment does hypertrophy and hyperplasia occur in
leptin-rich environment
45
what pathways does leptin activate, where, what is result
MAPK and STAT in preadipocytes promotes adipogenesis causing increased PPARi, lipoprotein lipase levels, fat storage
46
what is hypertrophy - 2
adaptive response to nutrient excess, diet dependent protects other tissues from lipotoxicity
47
what happens if hypertrophic threshold is passed (occurs in obesity)
ectopic lipid production in other tissues
48
effect of hypertrophic threshold being passed on adipocyte function - 3
hypoxia inflammation metabolic dysfunction
49
what is hyperplasia - 3
differentiation of preadipocytes influenced by transcription factors like PPAR(gamma) and CCAAT (enhancer binding protein alpha) diet and genetics thought to only occur at early development stages
50
what maintains insulin sensitive phenotype
macrophages esp il-10
51
how are macrophages and adipose tissue replenished
circulating monocytes
52
how are monocytes recruited in obesity (contributing to inc insulin resistance)
in obesity, triacylglycerides get broken down into free fatty acids, induces glycolysis and release of pro inflammatory markers as byproduct e.g. MCP-1 released into bloodstream, recruits monocytes to adipose tissue in adipose tissue, monocytes convert to pro inflammatory M1 macrophage these produce pro inflammatory cytokines released into bloodstream act in a paracrine fashion, cause insulin resistance in adipose tissue - by activating protein that inhibits protein involved in insulin signalling pathway
53
pro inflammatory marker example
MCP-1
54
intermittent fasting and obesity
can improve obesity by inhibiting MCP1 / CCL2 production, redcuing pro inflammatory cytokines released
55
what is GLP-1
ozempic vibes drugs that suppress hormone glucagone like peptide-1 GLP-1 released after eating, makes u feel full resulting in people eating less
56
examples of organs GLP-1 receptors exist on
eyes intestines heart kidneys brain pancreas
57
other than organs, where do GLP-1 receptors exist
leukocytes: monocytes, etc
58
what is non alcoholic fatty liver disease NAFLD
new definition: metabolic associated fatty liver disease (MAFLD) build up of fat in liver causing hepatic lipotoxicity leads to serious liver damage and cirrhosis
59
risk factors of NAFLD or MAFLD - 5
obesity T2DM/ type 2 diabetes gut microbiota genetic environmental
60
do GLP-1R agonists promote pro or anti inflammatory cytokines
anti inflammatory cytokines downreg of CD36 (fatty acid transporter) and pro inflammatory cytokines inc in M2 like markers and anti inflammatory cytokines
61
health risks of obesity - 6
type 2 diabetes pregnancy complications - pre eclampsia or gestational diabetes coronary heart disease reduced fertility cancer asthma
62
obesity, NAFLD, and lipolysis
pts have inc lipolysis in adipose tissue abnormal production of hormones released from adipocytes e.g. dec adiponectin (adip is anti inflammatory) inc inflammation inc free fatty acids in liver (from both adipose tissue and diet) liver produces more lipids in compensation, induces elevated glucose uptake leads to inc SREBP-1c and ChREBP expression causing transciptional activation of lipogenic genes - these activate enzymatic machinery needed to convert extra glucose into free fatty acids to then be esterified to triglycerides free fatty acids can be released from triglyceride stores via autophagy or intracellular lipases to be oxidised in mitochondria forming ATP OR incorporated into VLDL via MTP
63
what is lipolysis
breakdown of triacylglycerides into glycerol and free fatty acids
64
how are free fatty acids released from triglyceride stores
free fatty acids can be released from triglyceride stores via autophagy or intracellular lipases
65
free fatty acids induce lipotoxicity. what can this cause - 5
ER stress - inc insulin resistance and cell death oxidative stress autophagy lipoapoptosis - of mitochondria as well as liposome inflammation overall, NAFLD progression
66
obesity and infection
more likely death and inc ICU length of stay inc infection susceptibility post operative complications reduced type 1 IFN inc pro inflammatory cytokines metabolic endotoxemia - like leaky gut syndrome if LPS leaks into system due to dec insulin resistance impairs T and B cell response
67
what are pulmonary lipofibroblasts
special type of adipocytes contain lipid droplets in alveoli vital role in prog of covid pts with obesity can differentiate into myofibroblasts to induce pulmonary fibrosis - lung disease when lung tissue becomes damaged, scarred, lungs canny work properly and short of bref
68
what regulates FFA uptake into adipocytes
insulin
69
what does inflammation promote - 2
insulin resistance and FFA deposits
70
what occurs first - hypertrophy or hyperplasia
trophy
71
what hormone does WAT release
adiponectin
72
what is adiponectin
hormone released by WAT acts in brain to inc metabolism and breakdown of fat, inc energy use in muscles reduce body weight
73
in lean state, what are macrophages normally in the state of
M2, secreting il-10 for insulin sensitivity

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