KIN 404 3 Flashcards
Is obesity a result of hypertrophy or hyperplasia?
Adipocyte number increases in childhood and adolescence then levels off and remains constant in adulthood in both lean and obese (early onset) individuals.
What does weight loss from bariatric surgery stem from?
Major weight loss by bariatric surgery results in a significant decrease in cell volume but fails to reduce adipocyte cell number
What is fat mass determined by?
Both adipocyte number and size
Steps in the development of obesity (process through hypertrophy and hyerplasia)
1) Mesenchymal cells 2) preadipocytes 3) adipocytes filled with small lipid droplets 4) adipocyte with one large lipid droplet encompassing greater than 90% of the entire cell body 5) Adipocytes can enlarge up to 1000 times their original size (hypertrophy) and once it reaches a certain size it triggers other preadipocytes to differentiate, increasing the number of adipocytes (hyperplasia)
Once a preadipocyte becomes an adipocyte can it become anything else?
Nope…the change is permanent
How many adipokines does adipose tissue secrete?
50+ adipokines
What are the adipokines that contribute to insulin resistance in an obese state?
TNF-alpha, IL-6, FFA, MCP-1, TIMP-1, and RBP4
What 2 body masses cause type 2 diabetes?
Both obesity and lipodystrophy cause severe defects in lipid and glucose homeostasis resulting in peripheral insulin resistance and type 2 diabetes
Steps in the mechanism is which fatty acids cause insulin resistance T2D
- Positive net energy balance leads to TG accumulation in many tissues 2) Increased TG in adipose tissue leads to increased lipolysis by a mass effect which in association with adipocyte insulin resistance leads to 3. net spillover of fatty acids to nonadipose tissue which leads to the 4. insulin resistant state and type 2 diabetes
What is normal insulin signaling and the regulation of glucose and lipid homeostasis like in a healthy state?
Insulin is released from the pancreas in response to elevated blood glucose following a meal. It decreases hepatic glucose output and lipolysis in adipocytes, while increasing glucose uptake into muscle and liver and increasing fatty acid synthesis in adipocytes.
What is metabolic flexibility?
Ability to switch fuel use (fat vs. carb) under appropriate nutritional condition (fast vs. fed)
How are obese people/T2Diabetics metabolically inflexible?
They primarily use glucose (high RER) in a fasted state when they should be oxidizing fat (low RER), so in response to insulin, they can’t increase carbohydrate metabolism
What is the role of insulin in the stimulation of adipose tissue fatty acid uptake, esterification and storage?
It inhibits HSL, which decreases lipolysis. It increases lipoporitein lipase activity and fatty acid uptake. It increases glucose uptake (for glycerol-3-P). It may also increase DGAT activity. All of this leads to increased intracellular TG and decreased lipolysis.
What are the 2 ways that glucose is transported into muscle?
Insulin-stimulated and contration-stimulated
Muscles stimulated with supramaximal insulin plus exercise have greater transport than either alone…what does this illustrate?
Insulin and exercise use distinctive mechanisms to increase glucose transport in muscle
What activates PI3K?
Insulin
What activates AMPK?
Exercise
PI3K inhibitor blocks effects of….
insulin but not exercise
Muscles from ZUcker rats are insulin resistant but…
have normal contraction stimulated glucose transport
Mice with expression of inactive AMPK…
contractile glucose uptake is inhibited but insulin mediated is fine
LKB1 knockout mice…
contractile inhibited, but insulin mediated is fine