5070: OBESITY

what type of disease is obesity?

what type of care does this require- short term? long term? lifelong?

chronicj

lifelong care

obesity is what type of disease (what does it effect?) x 2 things

metabolic and brain disease

what are 4 characteristics/descriptors of obesity as a disease?

chronic, relapsing, multi-factorial neurobehavioral disease

what happens during obesity?

what does this result in?

increase in body fat promotes adipose tissue dysfunction

adverse metabolic, biomechanical and psychosocial health consequences

what is the definition of BMI?

what 2 things does this relate?

body mass index

relationship between a person’s height and weight

what can’t BMI distinguish between? x 3 things

fat, muscle, bone

regarding where fat is located, BMI can’t tell us what two locations fat could be ?

visceral adipose tissue

central adipose tissue

what are demographic identifiers that BMI doesn’t account for ?

doesn’t account for age, sex, race, ethnicity

what is the range of BMI to consider when classifying if someone is obese?

30 < BMI < 34.9

How many adults were classified as obese in the US in 2018

42.4%

How many americans were obese in 1976-1980 survey of obesity?

15%

in 2018, how many children and adolescents were classified as obese?

19.3%

are a greater % of women or men classified as obese?

women

what is the patho of obesity a combination of?

genetics, environement, metabolism, neural circuitry

what is the prader-willi syndrome?

what does it cause? x2 things

defect of chromosome 15, causes constant hunger, uncontrollable eating

common obesity has this type of genetic influence

polygenic

in almost every human chromosome a locus was found that linked to _____.

predisposition to obesity phenotype

what are 2 other theories of obesity patho?

gut microbiota

thrifty gene hypothesis

what does the thrifty gene hypothesis mean?

during times of fluctuating food availability, weight was gained when food was plentiful and those energy stores were used when food was scarce

when there is plentiful food supply, this becomes maladaptive

what are some environmental factors about obesity? x 3 things

abundance of sugary/salty/fatty foods

increased portion sizes

proliferation of fast food restaurants

what meal of the day is the most popular for fast food?

lunch

what do adipocytes do? x2 things

store fat in the form of triglycerides

release triglycerides to be used for energy/fuel when needed

during conditions of energy excess, what do adipocytes do? x2 things

proliferate or hypertrophy

hypertrophy is considered what type of response to energy excess?

maladaptive

what is adiposopathy, or sick fat? x2 things

hypertrophy of adipocytes with visceral fat accumulation

what happens when adipocytes are so large that their diameter exceeds the diffusion limit of oxygen?

what could this develop into?

localized hypoxia

could cause necrosis/apoptosis, attracting macrophages and promoting chronic inflammation

what does central obesity look like?

what is the fruit shape of this?

fat distributed primarily on the trunk

apple shape

what does peripheral obesity look like?

what fruit is this associated with ?

primarily on the hips and limbs

referred to as pear shape

if the capacity of adipocytes to store fat is exceeded, where will the fat be deposited?

in, on, around lean organs like heart, kidneys, liver

what is ectopic fat?

fat stored in, on and around organs

what is visceral fat?

internal abdominal fat, intra-abdominal, mostly in the mesentary, ectopic

what type of obesity is often a strong indicator of underlying visceral fat?

central obesity

subQ fat is found where?

what type of obesity is it typically associated with?

under the skin

peripheral obesity

what type of adipose (visceral/subq) is more hormonally active and more inflammation-promoting ?

visceral

what type of adipose is pro-inflammatory?

visceral adipose

adipose tissue has what 2 endocrine functions?

release of cytokines/adipokines

adipose tissue produces multiple hormones and cytokines that promote what 6 things?

what type of adipose tissue is this especially true for?

insulin resistance, inflammation

HTN

atherosclerosis, thrombosis

create conditions that promote development and maintenance of obesity

visceral adipose tissue

what is the normal function of leptin? x 3 things

increase satiety and energy expenditure

increase insulin sensitivity

under conditions of increased and/or hypertrophied adipocytes, what hormone is produced in excess?

leptin

what does too much leptin lead to ?

leptin resistance

what is leptin resistance?

brain and the body fail to respond to leptin properly w regard to satiety and energy expenditure

leptin is also considered an overall ______ cytokine, that does _____.

pro-inflammatory cytokin

upregulates adaptive/innate immune systems, including activity of macrophages

what 4 things does adipsin do?

stimulate insulin production

preserves pancreatic B cell function/survival

facilitates glucose uptake

increases triglyceride synthesis in adipocytes, inhibits lipolysis in adipocytes

during conditions of obesity, adipsin production is increased or decreased?

decreased

what kind of overall action does adipsin have?

what does this decrease the risk of?

overall anti-hyperglycemic action

decreased risk of diabetes

adiponectin normally stimulates what?

what affect does this have in the body and what does this help do?

the production of nitric oxide in vasculature

increases the antiatherogenic activities of the vascular endothelium

helps prevent atherogenesis and is considered anti-inflammatory

when fat mass increases, what does the amount of adiponectin do?

what does this promote?

decreases

promotes atherogenesis

what role do hypertrophied adipocytes play in the production of adiponectin?

their large size induces the transceiption factors that increase transcription of genes coding for angiogenic growth factors and which inhibit adiponectin gene transcription

what is atherogenesis?

the formation of subintimal lipid-containing plaques in the lining of arteries

what does MMCP-1 stand for?

macrophage and monocyte chemoattractant protein 1

what does MMCP-1 do, how does it do this? x2 things

promotes inflammation by activating macrophages resident in adipose tissue

increases insulin resistance

what is the function of resistin?

increases insulin resistance

what is the function of plasminogen activator inhibitor-1

what does this mean?

inhibits the breakdown of fibrin clots

it is pro-thrombotic

what is the function of TNF-a?

promotes inflammation and increases insulin resistance

what is the function of IL-6 ? x 4 things

promotes inflammation

increases insulin resistance

increases hepatic lipid and glucose production

identified angiotensin II and aldosterone have been found in adipose tissue to cause what?

hypertension

what do hypertrophied adipocytes release lots of ?

free fatty acids (FFA’s)

what do excess FFA’s do in the body?

what does this result in?

overwhelm the normal metabolic pathways

leads to toxic intermediates that interfere with normal insulin signaling and GLUT4 functions

with regard to insulin, what do excess FFAs contribute to?

insulin resistance

what do excess FFAs attract?

what do these release and what does this cause?

attract macrophages

they release TNF-a

results in increased inflammation

obesity can cause sleep apnea, which causes sleep deficit in patients. What does this lead to regarding leptin and ghrelin?

decreased leptin and increased ghrelin

what organ is ghrelin produced by?

what is the action of ghrelin?

a hormone produced by the stomach

stimulates appetite

what does MASLD stand for ?

metabolic dysfunction -associated steatotic liver disease

what is MASLD?

fat droplets accumulate in the liver cells, causing swelling and damage to the liver

what is MASLD?

a sequelae of obesity

how does obesity influence when someone gets COVID-19?

obesity increases the risk of severe illness with COVID-19

how is obesity connected to diabetes?

through insulin resistance

all cause mortality rises especially fast as BMI goes over what levle?

35

children with obesity have what risk of developing diabetes?

what is the risk of developing diabetes in obese adolescents vs those with adult-onset obesity

increased

increased risk than in adults

can children develop MASLD?

yes, 70-80% have have MASLD

regarding atherosclerosis, what is the connection with obesity in children

have early evidence of atherosclerosis

what is metabolic syndrome? x 4 things

central obesity

dyslipidemia

increased BP

hyperglycemia

what does MetS do regarding risk for another disease?

increases the risk of cardiovascular disease

a person must have 3 or more of the what 5 characteristics to be defined as having MetS

waist size

triglycerides >150 mg/dL

HDL cholesterol

blood pressure > 130/85 mm Hg

fasting blood glucose > 100 mg/dL

can normal-weight people have MetS?

yes

fructose is what?

part of the disaccharide sucrose

what are chylomicrons, and what are they made of?

where are they synthesized?

lipoproteins, composed of triglycerides

GI tract

what is the travel pattern of chylomicrons (where synthesized, where they enter, where they travel)? x 3 steps

synthesized in the GI tract

enter the GI lymph vessels

travel to thoracic duct to enter the bloodstream

chylomicrons travel in circulation to deliver what to tissues?

triglycerides

what does lipoprotein lipase do?

what can the products do?

breaks down triglycerides from VLDLs and chylomicrons into fatty acids

they can diffuse into the adipocyte and re-form triglycerides with glycerol

what tissue is lipoprotein lipase particularly found in?

adipose tissue

what are lipoproteins?

a protein membrane surrounded by a core of lipids

what do lipoproteins transport? x 3 things

cholesterol, triglycerides, other lipids

what characteristic of lipoproteins allow it to travel easily through the plasma?

hydrophilic shell

what do chylomicrons carry from and to?

triglycerides from dietary intake from GI system to the liver and other tissues

what is the function of VLDL?

Delivers triglycerides to tissues

what is the function of LDL?

what does it play a major role in that gives it the ‘bad cholesterol’ name?

delivers cholesterol to tissues

major role in atherogenesis in blood vessels

what does HDL do?

what name does this earn it?

‘reverse cholesterol transport’ and brings cholesterol back to the liver

“good cholesterol”

where is LDL-C recycled?

in the liver

what is HDL also known as?

good cholesterol

what is the definition of dyslipidemia? X3 THINGS you need

abnormal blood lipid panel with

high triglycerides

high VLDL or LDL

low HDL

what is dyslipidemia also used interchangeably with?

hyperlipidemia

with dyslipidemia, excess fatty acids can circulate, which can contribute to what?

insulin resistance

hormone sensitive lipase promotes what?

where is the product released and taken up?

the lipolysis of triglycerides in adipose tissue into glycerol and free fatty acids

released into bloodstream and taken up by the liver

how much dietary cholesterol is absorbed?

50%

what is the definition of incretin?

hormones released when stimulated by glucose ingestion

GLP-1 AND GIP both generally do what in the body?

increase insulin secretion

what is the most likely reason that semaglutide is helpful with weight loss?

mechanism of GLP-1 action and the neural reward circuitry

what is the abdominal gastric band bariatric surgery?

how effective is it compared to other types of surgeries? x2 things

band below gastro-oesophageal junction to create small gastric pouch with narrow stoma

patients have less weight loss with this, needs regular follow up for tightness control

what is the gastric sleeve bariatric surgery?

how often is this surgery preformed?

part of the stomach excised and removed

the most often surgery