Adipose Tissue, Inflammation and Obesity Flashcards
What is the BMI level to categorise men/women with obesity ages 18 and over? - WHO
> 30kg/m^2
What is the prevalence (%) of obesity in the UK? - National Obesity Observatory (Nov 2011)
26.1% (2010)
What are the 3 main reasons that obesity is an issue?
- It is widespread
- Prevalence remains high
- Consequences are costly
In terms of the spread of obesity, how much of England is overweight/obese for: adults, 2-10yo, 11-15yo?
- two-third adults
- quater 2-10yo
- one-third 11-15yo
Define obesity:
Chronic adverse condition due to excess amount of body fat
Most widely used method to determine relative amount of body fat:
BMI
What is the metric BMI formula
weight (kg)/height^2 (m^2)
What are the types of body fat and their % storage?
- Subcutaneous fat (70-75%)
- Visceral Fat (10-15%)
- Ectopic Fat (10-15%)
What is ectopic fat?
Non-adipose tissue fat.
In the liver, skeletal muscles and heart
For subcutaneous, visceral and ectopic fat, what are their clinical clues, respectively?
- BMI
- Waist circumference, triglycerides
- ALT levels
What is the normal BMI range?
18.5 - 24.9
What is the BMI for being obese?
> 30
Purpose of measuring BMi:
to see the level of risk in mortality
Where is fat accumulated in individuals with poor “fat health”?
- visceral compartment
- non-adipose tissue compartments (liver and heart)
Since ethnicity plays role in body fat%, what is the overweight and obese BMI threshold for the south asian community, respectively?
Overweight = 23 Obese = 25
What is the waist circumference cut-off for south asian women and men with obesity?
women - 80cm
men - 90cm
How much visceral fat (total body fat) do men have compared to premenopausal women?
2x
What is the relative risk of death in cardiovascular disease for women and men with highest WHR (waist-hip ratio)?
women - increased 8 times
men - increased only 2 times
What are the differences in adipose tissue in men and women?
- increase amounts of brown adipose tissue
- enlarged peripheral fat depots in women
- intra-abdominal fat depots increased in men
- metabolic/endocrine functions of depots differ, with diminished disease risk in women
At what waist-hip circumference in men and women poses increased risk?
men:
Low: <94cm
High: 94-102cm
Very high: >102cm
Women:
Low: <80cm
High: 80-88cm
Very high: >88cm
Describe a person at an obese BMI (metabolically healthy):
- Excess subcutaneous > visceral fat
- increase muscle/fitness
- hyperinsulinemia
- normal insulin sensitivity/blood sugar
- mild cardiovascular risk
Describe a person at an obese BMI (metabolically unhealthy):
- Excess subcutaneous > visceral fat
- Muscle loss (sarcopenia)
- hyperinsulinemia
- Diabetes
- Dyslipedemia
- Inflammation
- High cardiovascular/cancer risk
Whats the difference in description of metabolically unhealthy and healthy individual with normal BMI?
- chronic illness
- muscle loss (sarcopenia)
- excess visceral fat
- insulin resistance
- diabetes
- inflammation
- high cardiovascular/cancer risk
How would the classification of body fat based on BMI and metabolic health be?
- MUNO/MONW = metabolically unhealthy non-obesity/normal weight
- MUO = metabolically unhealthy obesity
- MHNO = metabolically healthy non-obesity
- MHO - metabolically healthy obesity
What can cause fat accumulation?
- genes
- excess energy intake
- physical inactivity
- environment
- behavior
What happens when the expandability of subcutaneous fat depots and adipocyte function is IMPAIRED?
- ectopic fat deposition @ visceral/liver/heart/etc
- proinflammatory adipocytokines increase
= unhealthy obesity
How do you preserve metabolic health in metabolically healthy obesity AT THE LIVER?
decrease liver lipid
How do you preserve metabolic health in the metabolically healthy obesity AT THE GI tract?
- decrease visceral adiposity/inflammasome activity/macrophage-specific t-cell signature
- increase incretin response to meals
- favourable metagenomic signature
How do you preserve metabolic health in the metabolically healthy obesity AT VESSELS?
- decrease systemic inflammation
- increase adiponectin
How do you preserve metabolic health in the metabolically healthy obesity AT MUSCLES?
- increase metabolic flexibility
- specific lipidomic signature
How do you preserve metabolic health in the metabolically healthy obesity at ADIPOSE TISSUE?
- decrease macrophage-specific t-cell signature
- health adipose tissue expansion
- better mitochondrial function
What was the prevalence % of overweight indians which was intepreted as under-diagnosed for overweight/obese patients?
75%
What are the diagnostic factors for clinical examination of obesity?
- height
- weight
- waist circumference
- hip circumference
- comorbid conditions
What are possible comorbid conditions of obesity?
- TD2, CVD, HTN
- hyperlipidaemia
- hiatal hernia
- asthma, obstructive sleep apnoea
- stroke, gout, arthritis
- cancer
urinary incontinence - gallbladder disease
- depression
What further investigations can be made to diagnose patients?
- FBC (full blood count)
- serum transaminases
- thyroid function tests
- ECG
- abdominal ultrasound scan
- polysomnography (sleep study)
What does the elevated waist circumference indicate?
- risk for obesity-related disease
- high risk of hypertension/diabetes/dyslipidaemia/metabolic syndrome
What are the types of body composition tests?
- skinfold measurement
- hydrodensitometry
- bioelectrical impedance analysis
- DXA
What does a BMI z-score indicate?
how many units (of a SD) a child’s BMI is above or below the average BMI value for their age and sex
What is the general cut off points for children BMI?
Underweight: ≤2nd centile
Healthy weight: >2 - <85th centile
Overweight: ≥ 85th centile
Obese: ≥95th centile
What assessment is not used to gauge BMI of children?
Waist circumference
Where are white and beige adipocytes derived from?
Pax7-
Myf5-
via distinct precursor cells
Explain the differentiation process of beige adipocytes:
- following activation by cold/other inducers
- then cell become inactive when the cold challenge is removed
- then take morphology of “white” adipocyte
What lineage do classic brown fat come from?
Pax7+ and Myf5+, shared with skeletal muscle
Explain the adipocyte metabolism:
- After meal, triglycerides (TG) packaged into chylomicrons and transported to adipocytes
- LPL produced by adipocytes secreted to capillary endothelium - cleaves TG
- TG are taken up by adipocyte and esterified
- Insulin stimulates this process, mainly by stimulating glucose uptake
- process of lipolysis is stimulated by catecholamines and inhibited by insulin
What do healthy adipose tissue buffer?
the daily influx of dietary fatty acids
What type of effects result from secreting variety of adipokines?
autocrine, paracrine and endocrine effects
Is adipose tissue a metabolic organ?
YES
Is adipose tissue an endocrine organ?
YES
What is the function of adipose tissue?
- prevents insulin resistance
- lipid metabolism
- insulin sensitivity
- glucose homeostasis
- inflammation immunity
- blood pressure regulation
- angiogenesis
- vascular homeostasis
- appetite
- energy balance
What is the result of enlarge adipocytes with reduced buffering capacity for lipid storage?
- exposes other tissues to excessive influx of lipids
- lead to ectopic fat deposition
- insulin resistance where energy intake exceed EE
- lipodystrophy
- obesity
- impaired insulin secretion
Explain what happens to adipocytes in overnutrition:
- Adipocytes increase in size
- Further expansion limited by matrix
- Matrix undergoes fibrotic change
- Triggers changes: hypoxia, inflammation, cell death - all contribute to insulin resistance
What happens when adipose tissue BLOOD FLOW is decreased in obesity?
- lipid handling affected
- excessive fat storage in non-adipose tissues
- hypoperfusion may induce hypoxia
Describe what happens in adipose tissue hypoxia:
there’s disturbance in adipokine secretion and increased macrophage infiltration in adipose tissue
What are the general roles of adipocytes?
Store and release calories to the body
may have additional roles of fat in a wide array of biological processes
How do adipocytes affect the heart?
increases atherosclerosis/blood pressure
How do adipocytes affect the muscle?
- regulation of insulin sensitivity
- regulation of browing by myokines
- intramuscular adipocytes affect muscle function
How do adipocytes affect the skin/hair?
- Improved wound healing
- regulation of hair growth
How do adipocytes affect the lymphatics?
- lymphatic fluid promotes fat accumulation
- adipocytes provide nutrient to local lymph nodes
How do adipocytes affect the bone marrow?
- increase marrow fat associated with osteoporosis
- decreased hematopoiesis
How do adipocytes affect cancer?
- adiposity positively associated with tumour growth
- metastasis