FORM & FUNCTION (Obesity 1)

Question 1

Obesity:

Answer 1

-over-accumulation of adipose tissue
-increased risk for metabolic disorders (ex. diabetes, steatosis)
-associated with various endocrine alterations (thyroid, insulin, etc.)

Question 2

Overweight and Obese BW:

Answer 2

-overweight: over 15% of optimal
-obese: over 30% of optimal

Question 3

Percent of dogs, cats and horses that are overweight or obese:

Answer 3

-dogs: 35-40%
-cats: 25-35%
-horses: 27-35%

Question 4

Fundamental cause:

Answer 4

-multiple risk factors
-human sociological factors
*when caloric intake is way greater then energy expenditure (metabolism)

Question 5

Multiple risk factors:

Answer 5

-breed
-age
-sex hormones (neuter/spay
-metabolic disorders (ex. hypothyroidism, hyperadrenocorticism)
-medication (ex. steroids, anticonvulsants, antidepressants and more)

Question 6

Sex hormones (neuter/spay)

Answer 6

-excess early weight predispose animal to adult obesity (1.5x)
>due to reduction of sex hormones when they are spayed/neutered

Question 7

Human sociological factors:

Answer 7

-feeding = means of communication
-lifestyle (of owner)

Question 8

Obesity is a difficult topic:

Answer 8

-more about communication issues than medical
-only 50% of owners know their pets have a weight problem
-MANY believe that food intake has nothing to do with obesity
>will blame inactivity but not too much food!

Question 9

Fat from digestive CHO, protein or lipids

Answer 9

-excess from diet ends up becoming fat

Question 10

Fat molecules:

Answer 10

-very metabolically active
>they will grow over time
-they are an endocrine organ when they hypertroph

Question 11

Fat that has hypertrophied:

Answer 11

-attracts macrophages, lymphocytes, neutrophils and other immune cells
*’adipokines’ dysfunction

Question 12

High circulating fat with inflammatory markers eventually leads to:

Answer 12

-pancreatitis (pancreas inflammation)
-cirrhosis (liver scaring)

Question 13

(white) adipose tissue:

Answer 13

-classically though as an organ that ONLY serves to store energy and provid insulation
-recent evidence shows it is an endocrine organ

Question 14

Adipose tissue: endocrine organ

Answer 14

-controls energy metabolism via hormone and cytokine release (adipokines)
>release of hormones and cytokines can have a hug impact on the body

Question 15

Leptin: peptide hormone

Answer 15

-made from fat
-secreted into the blood
-acts on the brain
-level is proportional to fat level

Question 16

Leptin after high fat diet:

Answer 16

-increases for around 8hrs then decreases back to normal state

Question 17

Major function of leptin:

Answer 17

-regulate appetite (signals to brain to stop eating)
-slow down fat synthesis
-promote fate break down (beta-oxidation)

Question 18

Leptin and obesity:

Answer 18

-ob/ob alleles
-inability to make it OR development of leptin resistance DIRECTLY leads to obesity

Question 19

Leptin in liver:

Answer 19

-controls fat metabolism by stimulating AMP kinase activation (AMPK)
>acts to slow down FA biosynthesis by inactivating ACC via AMPK
*promotes fat usage rather than storage

Question 20

Leptin in muscle:

Answer 20

-stimulates beta-oxidation to reduce body fat mass
>inhibits AMPK and therefore ACC to reduce malonyl CoA accumulation
>reduction of malonyl-CoA will allow for beta-oxidation to continue

Question 21

No FAS in muscle (leptin):

Answer 21

• but malonyl-CoA are still synthesized by ACC when acetyl-CoA are in excess
  *high malonyl-CoA inhibits carnitine attachment=inhibits beta-oxidation

Question 22

Circulating leptin levels in obese animals:

Answer 22

-constitutively high
*due to development of leptin resistance

Question 23

Leptin resistance:

Answer 23

-not leptin deficient, but diminished end-organ response
-primarily impairs the satiety effect, but can diminish AMPK regulation in peripheral tissues (liver, muscle)

Question 24

Tumour necrosis factor-alpha (TNF-a)

Answer 24

-when high levels it disrupts insulin function via 2 mechanisms
-cytokine
-levels are increased when fat is elevated

Question 25

Development of insulin resistance:

Answer 25

-leads to cells not properly storing glucose/fat
-then leads to progression towards diabetes and steatosis

Question 26

2 mechanisms how TFN-a disrupts insulin function:

Answer 26

-inhibits IRS-1
-inhibits PP1

Question 27

TNF-a inhibits IRS-1:

Answer 27

-normal: required for GLUT4 activation
-impairs glucose uptake in muscle and fat

Question 28

TNF-a inhibits PP1:

Answer 28

-impair glycogen and fat formation (via inhibition of protein phosphatase 1)
-disrupts insulin’s inhibitory effect on hormone-sensitive lipase

Question 29

TNF-a in obese dogs:

Answer 29

-elevated levels
-insulin resistance development
*more insulin required after a meal to process glucose
-very little changes in pre meal insulin, but changes in post meal insulin
>overtime triggers insulin resistance and leads to type 2 diabetes

Question 30

Obesity effects:

Answer 30

-joint disorders
-osteoarthritis
-diabetes mellitus
-reduced life span