Obesity and Metabolic Syndrome Flashcards
Adipose tissue can be found
Most around visceral organs
Adipose tissue is made of
adipocytes
Adipocytes are used
1) to store TAGS (triacyglycerol)
2) For lipid homeostasis and maintenance of energetic metabolism
Increase of fat mass occurs in 2 ways
1) Hyperplasia: Enlargment of an organ or tissue because of cell proliferation (more cells)
2) Hypertrophy: Enlargment of an organ or tissue from increase in size of its cells
What two tissues expand through hypertrophy and hyperplasia
1) Subcutaneous adipose tissue (SAT)
2) Vicsceral adipose tissue (VAT)
T or F: Hyperplasia has a protective effect against obesity-associated metabolic complications.
T
What happens to unhealthy individuals in terms of hyperplasia
1) In unhealthy obese individual, hyperplasia of adipocytes in SAT is compromised, limiting the storage capacity of fatty acids.
2) The excess lipids will be stored in VAT as well as ectopic tissues, leading to lipotoxicity.
3) The lipotoxicity will take multiple forms: hypoxia, inflammation, insulin resistance which causes
Metabolic syndrome, type 2 diabetes, heart disease.
Adipogenesis and obesity (healthy vs unhealthy adipogenesis)
Energy homeostasis
Maintains amount of adipose tissue at a healthy level
Energy homeostasis
Maintains amount of adipose tissue at a healthy level
Purpose of thermic effect of food
Thermic effect of food is the energy necessary to process, digest, absorb and store nutrients in the body
T or F: Total energy expenditure over a lifetime is constant
True
Obesity BMI
BMI greater than 30, overweight (25-29.9)
Obesity (especially visceral obesity) increases the risk of developing other diseases like
-Cardiovascular disease (heart attack, stroke)
-Type II Diabetes
-Sleep apnea
-Fertility problems
-Osteoarthritis
-Cancer (Breast, colon, prostate, endometrium, kidney and gallbladder)
Adipokines
Signaling molecules important in many physiological and metabolic processes. Mostly produced by adipocytes…but also resident macrophages
Physiological and metabolic processes regulated by adipokines secreted by adipocytes
Physiological and metabolic processes regulated by adipokines secreted by adipocytes
The hypoxia theory
1) As adipose tissue mass expands (obesity), groups of adipocytes will become more and more distant to blood vessels.
2) Increase in adipose tissue does not lead to an increase in blood flow to this tissue
3) Hypertrophic adipocytes (150-200mm in diameter) are larger then the normal diffusion distance of O2 (100-200mm in diameter)
4) Under hypoxic conditions, a variation of expression in adipokines is observed.
Effects of hypoxia on the secretion of key adipokines by human adipocytes in cell culture
What is induced by hypoxia/obesity
HIF-1a (hypoxia inducible factor-1a) expression
HIF1α is linked to Cancer
Rapid growth of tumour and hypoxic conditions found by degradation of HIF1α
T or F: HIF1α regulated experssion of 1300 genes and decreases the release of which adipokine
Adiponectin
Effects of hypoxia on adipokine expression
explain obesity and metabolic syndrom
Metabolic syndrome is a cluster of conditions — increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels — that occur together, increasing your risk of heart disease, stroke and diabetes. (Mayo Clinic)
Group of risk factors that raises your risk for heart disease and other health problems.
What are 3 mdtabolic consequences of obesity
1) Regulation of body weight
2) Inflammation
3) Insulin resistance
T or F: Leptin regulates body weight
True
Leptin
An adipokine secreted by the adipose tissue that is involved in multiple processes including the control of appetite, the rate of of b-oxidation and FA synthesis in the various tissues.
Control of appetite by leptin
What happens if we remove the LEP (Leptin) gene from a mouse genome
Mice become obese
Suffer from hyperphagia (abnormal increase in appetite)
What happens if we remove the LEP (Leptin) gene from a mouse genome
Mice become obese
Suffer from hyperphagia (abnormal increase in appetite)
t or F: Obese individuals do not develop resistance to leptin
False they do and leptin is a long term response so have increased leptin but stop responding (hyperleptinaemia)
Obesity and inflammation
Obesity and inflammation
TNF-α is secreted by
adipose tissue-resident macrophages
Action of TNF-α (pro inflammatory response)
1) Stimulates lipolysis
2) TNF-α counteracts the action of insulin (prevents binding to the receptor and lowers the expression of GLUT4)
3) Block the entry of new free fatty acid.
4)Decrease TAG biosynthesis through inhibition of the peroxisome proliferator-activated receptor gamma (PPARγ)
Summary of Action of TNF-a in regars to Insulin signaling
1) The TNF-α pathway stimulates the expression of proinflammatory genes but also blocks the downstream activation of insulin signalling by inhibiting the kinase activity of IRS1.
2) IRS1 can be destabilized by the Interleukin-6 (IL-6) signaling cascade.
3) Higher concentrations of IL-6, which is an adipokine, are observed in obese individuals.
Explain the interleukin-6 (IL-6) paradox
1) In healthy subjects, 10-35% of the circulating IL-6 is produced by adipose tissue (mainly by adipose resident macrophages).Levels of IL-6 increase in response to acute and low-grade chronic inflammation.It was shown that a transient/acute expression of IL-6 in response to exercise was causing an increase in sensitivity to insulin.
2) On the other hand, multiple studies have also shown that chronic elevated level of IL-6 was leading to a decrease in insulin sensitivity. Obese individuals display a chronic elevated level of IL-6.
Explain obesity and m,etabolic consequences (insulin resistance)
obesity leads to an adipokines imbalance, which in turn causes the body to be in a proinflammatory state. Over time, it will cause cells/organs to become insulin resistant. Insulin resistance will develop into type 2 diabetes.
Effects of insulin
3 consequences of insulin resistance
Adiponectin (Acrp30)
Peptide hormone (adipokine) produced uniquely in adipose tissue.
Function of adiponectin (Acrp30)
When add adiponectin back = decrease gluconeogenesis and can use glucose again
Adiponectin is [blank] in obese indivdiuals and why
Decreased because adiponectin is secreted by visceral fat which obese levels have decreased levels of (VAT and SAT communicate with one another) so if one decreases the other increases
T or F: Adiponectin decreases insulin sensitivity
False, increases
Adiponection can bind to 2 receptors
1) AdipoR1
2)AdipoR2
AdipoR1
-Expressed mainly in the liver, muscle and hypothalamus
-Function: Activation of AMPK.
-Binds to the globular portion of adiponectin
AdipoR2
-Expressed mainly in the liver, WAT and vasculature.
-Function: Activation of PPAR (α, δ, γ)
-Binds to the full-length adiponectin
Adiponectin activates
1)AMPK
2)PPAR
Roles of adiponectin
How does adiponectin protect against atherosclerosis
= prevents inflammation
Obesity [blanks] PPARs concentration
decreases
Function of PPARs
These transcription factors respond to change in lipids coming from the diet by regulating the expression of genes involved in fat and carbohydrates.Their translocation to the nucleus requires the binding of a fatty acid (or fatty acids derivatives).
Function of PPARs
These transcription factors respond to change in lipids coming from the diet by regulating the expression of genes involved in fat and carbohydrates.Their translocation to the nucleus requires the binding of a fatty acid (or fatty acids derivatives).
3 types of PPAR and function
3 types of PPAR and function
PPARy is essential for the differentiation of
preadipocytes
Summary of regulation of inflammation, insulin resistance, and atherosclerosis in terms of obesity
Summary of regulation of inflammation, insulin resistance, and atherosclerosis in terms of obesity
