7 Fat Flashcards
What is the “old view” of fat?
Fat is a passive organ that is a DEPOT for fat storage
“Fat” refers to lipids and cells/tissues that store lipids
What is the “modern view” of fat?
Fat is a DYNAMIC organ
Energy conversion and storage Regulates energy balance and nutritional homeostasis Generates heat (“brown fat”) Cushions organs Affects body shape and appearance
What is adiposity?
How fat deposition occurs in the body
How is BMI calculated?
BMI = weight (kg) / height (m^2)
Or
BMI = weight (lbs) x 703 / height (inches^2)
BMI>30
Obese
BMI = 25-29.5
“Overweight”
BMI = 18.5 - 24.9
Health lean
BMI<18.5
Underweight
What happens to BMI with age?
Increases
What is the definition of obesity
Clinical state of excessive accumulation of body fat
Usually based upon BMI (>30)
The condition of abnormal lipid levels and/or their lipoproteins
Dyslipidemia or hyperlipidemia
Can be elevated cholesterol and triglycerides or elevated chylomicrons and LDL
White adipose tissue can be subdivided into …
Visceral vs subcutaneous white adipose tissue
Which is more dangerous: visceral or subcutaneous fat
Visceral
Obesity is associated with…
Heart disease
Stroke
Diabetes
Cancers
36.5% of US adults are obese
What groups are disproportionally obese?
Non-Hispanic blacks (48.1%)
Middle age (40.2% vs young adults 32.3%)
What are the three types of adipocytes?
White, Brown, Beige
What are the two types of fat deposits?
White adipose tissue (WAT)
Brown adipose tissue (BAT)
What types of cells are found in WAT?
Adipocytes (~50% of cells)
Pre-adipocytes (~2% of cells) - these are adipo stem cells
Fibroblasts - connective tissue
Endothelial cells - circulatory
Nerve cells
Macrophages (M1 pro-inflammatory vs M2 anti-inflammatory)
Brown fat is a _______ organ
Heat-generating
Hormone dependent - requires UCP1 transcription and G-protein second messenger
Daily heat production: 27 kcal/kg body weight
What allows brown adipose tissue to directly transfer food energy into heat energy?
Uncoupling Protein 1 (UCP1)
Dependent upon both Epi and TSH
T4 enters, converted to T3, binds to receptor and transcription —> UCP1 production; UCP1 enters mitochondria and generates heat.
Brown fat is found predominantly in _______.
Infants
It decreases with age but adults still have some concentrated around neck, shoulders, lungs (F>M)
BAT contains numerous small lipid droplets, uncoupled mitochondria, and myoglobin
BAT activity can be increased in response to cold exposure or epi
What is Beige Fat?
Occurs in WAT, has INTERMEDIATE mitochondria, UCP1 and lipid droplets, heat production compared to BAT
Possible induction by T3 and epi, cold, hepatic bile acids, and ANP/BNP, skeletal muscle hormone Irisin
What hormone promotes storage of fats into adipocytes and stimulates anti lipolysis effect (FA—>TG)?
Insulin
Stimulates lipoprotein lipase to convert TG to FA
Stimulates GLUT4 to increase glucose uptake into adipocytes
Inhibits hormone-sensitive lipase
Results: Lower fatty acids and increased storage Increased glucose uptake into adipocytes Increased enzymes that produce fatty acids Increased fatty acid uptake Decreased lipolysis
What hormones stimulate a lipolysis effect (TG —> FA)?
Epinephrine, cortisol, glucagon, and GH
Epi acts via HSL and adipose tissue triglyceride lipase (ATGL)
Thyroid hormone also has some indirect effect:
Doesn’t directly regulate fuel metabolites b/c onset is too slow to rapidly adjust blood levels of nutrients
Women tend to have more ________ fat depots, whereas men tend to have more ________ fat depots
Women = Subcutaneous (Gynecoid Adiposity)
Blood drains to skeletal muscle and free fatty acids are utilized for energy during exercise
Men = Visceral (Android Adiposity)
Mental and messenteric
Blood drains to hepatic portal and free fatty acids are cleared by the liver
How does testosterone affect adiposity?
It decreases subcutaneous depots and increases visceral depots, particularly in men
How does insulin affect adiposity differently in men v women?
Higher whole body insulin sensitivity in women (increases adiposity)
Men are less sensitive to anti-lipolysis effects of insulin
Estrogens and androgens lower body fat and improve insulin sensitivity in both sexes
How does metabolic activity differ in different types of WAT?
Subcutaneous WAT in lean people —> active metabolic activity
Gluteal-femoral WAT tissue —> least active metabolic activity
Visceral WAT —> most active metabolic activity
How does sensitivity to sex hormones vary between the different types of WAT?
Subcutaneous WAT in lean people is LEAST sensitive
Gluteal-femoral WAT is ESTROGEN sensitive
Visceral WAT is TESTOSTERONE sensitive
How does macrophage activity vary between different types of WAT?
Subcutaneous WAT: 10-15%, mostly M2 anti-inflammatory
Gluteal-femoral WAT: 10-15%, mostly M2 anti-inflammatory
Visceral WAT: 40-60%, mostly M1 pro-inflammatory***
This is why visceral fat is the most dangerous
What is the difference between hypertrophy and hyperplasia of adipose tissue?
Hypertrophy = increase in volume
Can but by up to 1000x
REVERSIBLE
Hyperplasia = increase in the number of adipocytes
Generally occurs during first year of life, late pregnancy, and beginning of puberty
NON-REVERSIbLE
Cells derived from pre-adipocytes
Visceral obesity results from deposit in the …
Mental, mesenteric, and retroperitoneal fat depots
Visceral obesity is usually a sign that lipids are also being deposited ectopically (muscle, liver, pancreas), which could aggravate DM
What are the hormones of the adipose organ called?
Adipokines - Leptin and Adiponectin
Adipokines that is a metabolic regulator and feedback signal on appetite
Leptin
Adipokine that is for insulin sensitizing and anti-inflammatory hormone
Adiponectin
Promotes the uptake of beneficial lipids
Other than Leptin and Adiponectin (the two main adipokines), what other adipokines regulate glucose metabolism?
Resistin: associated with T2DM and elevated LDL
Omentin: plays crucial roles in the maintenance of body metabolism and insulin sensitivity, and has anti-inflammatory, anti-atherosclerotic, and CV protective effects
Visfatin: released from visceral fat, binds the insulin receptor and exerts a hypoglycemic effect (promotes insulin function)
Visceral or Subcutaneous: Leptin
SC>V
Stimulated by increased adiposity, targets hypothalamus to decrease appetite, protects body from too much lipid
Visceral or Subcutaneous: Adiponectin
SC>V
Stimulated by weight loss, targets muscle, liver, heart, and vessels to increase oxidation of FFAs and has anti-inflammatory effects
Beneficial effects on insulin resistance
Visceral or Subcutaneous: Tumor necrosis factor alpha
V>SC
Stimulated by engorgment of adiposites, acts on liver, muscles, adipocytes etc to decrease adipocyte mass and opposes insulin signaling
Visceral or Subcutaneous: Interleukin-6
V>SC
Stimulated by inflammatory cytokines, targets liver, muscle, and adipose tissue to oppose insulin signaling
What are the beneficial effects of Adiponectin?
Improves insulin sensitivity
Anti-inflammatory
Anti-atherogenic
Targets resting skeletal muscle to increase GLUT4
Has CV protective effects
Stimulates liver to promote glucose uptake and energy storage
***Autocrine signaling in adipose promotes adipogenesis and insulin-directed glucose transport
In mouse studies, over expression of Adiponectin in fat tissue leads to …
An increase in SC fat, and yet it protects against diet-induced insulin resistance
What are the pro-inflammatory adipokines?
TNFa
Interleukin-6
Interleukin-1 (regulatory, promotes tumor growth)**
One of the theories as to why obesity is associate with a higher cancer risk
What happens when fat gets inflamed?
Constraints on extracellular matrix and diffusion limited hypoxia —> necrotic conditions
Macrophages increase 10% to 50% of cells
M1 macrophages increase proinflammatory cytokines (ie TNFa), which inhibit insulin action
Chronic low-grade inflammation —> increased ROS
Associated with elevated risk of cancer and can exasperate T2DM
Where does Leptin signaling occur in the brain?
In the arcuate nucleus of the hypothalamus
Anorexigenic or Orexigenic: Melanocortins
Melanocortins (POMC) suppress appetite —> anorexigenic
Anorexigenic or Orexigenic: Neuropeptide Y (NPY)
Potent appetite stimulus —> orexigenic
Also decreases metabolic rate and suppresses fertility
Anorexigenic or Orexigenic: Agouti-related protein (AgRP)
Potent appetite stimulant —> orexigenic
Also decreases metabolic rate and suppresses fertility
Anorexigenic or Orexigenic: Ghrelin
When released from the stomach, it stimulates NYP and inhibits the action of Leptin and POMC —> Orexigenic
What are the anorexigenic inputs to the hypothalamus?
Leptin (secreted from adipose tissue, weight loss in obese individuals reduces Leptin)
Insulin inhibit NYP cells
Amylin slows gastric emptying and signals satiety
Peptide PTT produced by small and large intestine inhibits NPY neurons
Cholecystokinin (CCK) released from the mucosal lining of the small intestine in response to a meal signals satiety
What are the orexigenic inputs to the hypothalamus?
Ghrelin, the hunger hormone released by the stomach, peaks before food is eaten and falls immediately after a meal
Explain why Leptin resistance is now an alternative theory as to the cause of obesity
Normally, Leptin inhibits insulin secretion in a classic negative feedback regulation
Leptin stimulates liver gluconeogenesis by vagal stimulation, and muscle, heart, BAT glucose uptake via ANS-sympathetic NS
When the feed back is lost, hyperinsulinemia increases weight gain, aggravates DM, and elevates Leptin levels
In Leptin resistant over-weight individuals, the permeability of the BBB to Leptin is decreased, leading to increases in appetite
Why do Biggest Loser contestants have a much reduced metabolic rate
Leptin levels crashed by the end of the season, and only recovered to ~50% of normal after six years (the never get back up to normal metabolic rate levels because of Leptin resistance)
