Metabolic Changes In Obesity And Metabolism Flashcards
BMI cut off levels
<18.5 = underweight
18.5-<25 = normal
25-30 = overweight
> 30.0 = obesity
NOT a diagnostic tool for body fatness or the health of an individual
is weight (kg)/ height (m2)
Definition of obesity
A health condition where’re someone is significantly above his or her ideal healthy weight
Is a complex disease that involves and excess amount of body fat and leads to increase risk of health problems
Waist-to-hip ratio (WHR)
Normal Women = 0.8
Normal Men = 1.0
Measure waist circumference and then measure hip circumference
- higher than normal ratio for each sex = upper body obesity (“apple” or “android” shaped)
- *apple is at higher risk fro metabolic diseases and is more dangerous**
- lower than normal ratio for each sex = lower body obesity (“pear” or “gynoid” shaped)
- *pear is at lower risk of metabolic diseases and may actually be protective**
Difference between subcutaneous and visceral fat
Subcutaneous WAT
- primary role = energy storage
- insulin’s sensitive
- slower lipolysis and FFA release
- contain high MW adiponectin
- FFAs and adipokines are released into peripheral circulation first
- marker genes = SHOX2/EN1/GPC4
- is overall better for you, but still not great
Visceral WAT
- primary role = energy storage
- insulin insensative
- high lipolysis and FFA release
- contain high resistin
- high rate of metabolic activity but also secretes more pro-inflammation markers
- FFAs and adipokines are released directly into portal vein in the liver first
- marker genes = HOXC8/HOXA5/MCP1
- *is overall worse for you**
upper body obesity = excessive visceral WAT and abdominal subcutaneous WAT
Brown/brite adipose tissues
Primary role = energy expenditure/thermogenesis
- regulated by cold and adrenergic stimulation
- marker genes = UCP1/PRDM16/PGC1a
- *Is the best fat**
What are the metabolic changes in obesity?
Increases chronic FFA and blood lipids = leads to hyperlipidemia
Increases inflammatory cytokines and abnormal adipokines = leads to chronic inflammation
Increases leptin levels chronically = leptin and insulin resistance
What is ectopic fat accumulation?
Fat accumulation into new WAT due to excess FFAs in the blood
Includes
- liver organ = NAFLD/NASH
- pancreas tissue = Type 2 diabetes
- muscle tissue = type 2 diabetes
- endothelial cells and vessels = atherosclerosis and CVD
Dyslipidemia
Low levels of HDL cholesterol
Elevated TAGs
Elevated total and LDL cholesterol
Produces HTN
What are the genetic and environmental components of obesity
Adopted children body weight correlates with biological parents
- environmental NOT genetic
Identical twins have very similar BMIs regardless of environment
- genetic
Dizygotic twins DONT share any BMI similarities
- environmental NOT genetic
- *common chromosomal translocations associated with obesity**
- 16q12 on FTO gene = highest known rate
- TMEM18 gene on 2 chromosome = 2nd highest known rate
POMC deficiency
Autosomal recessive Deficiency that results in obesity and adrenocorticotropic hormone insufficiency
Very early onset of obesity and is severe
also shows red hair due to no pro-opiomelanocortin gene
Other monogenic obesity syndromes
1) Leptin deficiency
- autosomal recessive
- very severe and early onset obesity
- also shows hypogonadotropic hypogonadism
2) leptin receptor deficiency
- is identical to #1
3) PC-1 deficiency
- autosomal recessive
- severe and early onset of obesity
- also shows hyper proinsuilinemia, hypercortisolism, hypogonadism
4) NTRK2 deficiency
- autosomal dominant
- severe and early onset of obesity
- shows with mental retardation
5) MC4R deficiency
- autosomal dominant
- makes up 2.5% of all clincially obese patients
- variable onset but is severe
- no other additional phenotypes
Metabolic syndrome (syndrome X)
A cluster of metabolic disorders that includes at least 3 of the following
1) abdominal obesity (waist in men = >40 inch); (waist in women = >35 inch)
2) altered blood lipids
- triglycerides >150mg/dL
- HDL cholesterol <40 mg/dL in men
- HDL cholesterol <50 mg/dL in women
3) elevated blood pressure
- systolic >130 or diastolic >85 mmHg
4) insulin resistance/hyperglycemia
- fasting glucose >100 mg/dL
obesity alone is NOT = metabolic syndrome
Difference between normal adipose development, healthy adipose expansion and metabolically unhealthy adipose expansion
1) Normal adipose development and expansion
- contains preadipocytes and mature adipocytes
- contains resident macrophages
- contains insulin receptors
- low inflammation when healthy adipose expansion occurs
- NOTHING ELSE
2) metabolically unhealthy
- everything seen in #1 except
- high levels of inflammation
- low levels of insulin receptors (sometimes none)
- pro inflammation macrophages present
What is lipodystrophies?
Diverse group of clinical disorders characterized by a complete or partial lack of adipose tissue in certain body areas but is excess elsewhere
Produce the following metabolic abnormalities
- insulin resistance
- severe hyperlipidemia
- progressive hepatic steatosis
- increased metabolic rate
Treatment for obesity
1) negative energy intake to promote ulitilzation of stored fat
- decreases caloric intake
- exercise (increase energy expenditure)
2) pharmacological treatment
- orlistat = decreases absorption of fat in GI
- lorcaserin and phentermine w/ topiramate = promote satiety through serotonin signaling
- liraglutide = decreases appetite by activating glucagon like peptide receptor
- bupropion w/ naltrexone = increases norepinephrine so increases metabolism
3) surgery
- bariatric surgery = #1 in severe obesity (induces metabolic effects by less ghrelin and other unknown components. Also improves blood sugar control in diabetic)
