Obesity

Question 1

Obesity

Answer 1

Over-accumulation of adipose tissue.

Overweight: BW>15% optimal
Obese: BW>30% optimal

increased rick of metabolic disorders

Question 2

Fundamental causes of obesity

Answer 2

• Breed
• Age
• sex hormones (spay/neuter)- excess weight predispose animal to adult obesity
• metabolic disorders
• medication
• human factors such as feeding animal and lifestyle

**Caloric intake greater than energy expenditure

Question 3

Communication of obesity

Answer 3

Only 50% of owners think their pet has a weight problem. Many owners believe that it has nothing to do with food, and is all to do with inactivity .

Question 4

Body condition scoring

Answer 4

Over 5 on scoring

Obesity= increase in subcutaneous and visceral fat

Question 5

Where does fat come from?

Answer 5

1. Dietary carbohydrates
2. dietary protein
3. dietary lipid

Question 6

White adipose tissue

Answer 6

• Stores excess carbohydrates, proteins, lipids.
• very metabolically active, always growing
• endocrine organ after hypertrophy. Attracts neutrophils, macrophages, lymphocytes which result in mild chronic inflammation.
• release hormones and cytokines = Adipokines

Question 7

Leptin

Answer 7

Increases after eating a meal, and then will decrease back to normal after 8 hours.

Regulates appetite, decreases fat synthesis, increases fat breakdown/beta-oxidation

Question 8

Leptins role in liver

Answer 8

Stimulates AMP kinase which decreases acetyl-CoA carboxylase (ACC) and malonyl-CoA (which is needed for fat synthesis) therefore decreasing fat synthesis

Question 9

Leptin’s role in Muscle

Answer 9

Stimulates AMP kinase which decreases acetyl-CoA carboxylase (ACC) and malonyl-CoA. It isn’t possible to undergo fat synthesis in muscle because it doesn’t have FAS. But malonyl-CoA has a role in inhibiting beta-oxidation by inhibiting the carnitine transporter so leptin’s role in decreasing malonyl-CoA causes an increase in beta-oxidation and the usage of fat.

Question 10

Leptin resistance

Answer 10

Primarily impairs satiety but also can diminish AMPK regulation in peripheral tissues

Question 11

Tumour necrosis factor- alpha

Answer 11

Cytokine released by adipose tissue. Disrupts insulin function via 2 mechanisms

1. Inhibits IRS-1 which prevents GLUT 4 activation in muscle and fat
2. Inhibits PP1 which impairs glycogen and fat formation and disrupts insulins inhibitory effect on hormone sensitive lipase promoting fat breakdown.

Question 12

Insulin requirement in obese animals after meal

Answer 12

They will require more insulin after a meal to process glucose

Question 13

Randle Cycle

Answer 13

The body has excess nutrients, and will prioritize using whichever fuel is the most abundant between carbohydrates and fat.

Question 14

How does excess lipid (obesity) block glucose metabolism?

Answer 14

1. Ingest fat –> High FFA beta oxidation increases mitochondrial levels of acetyl-CoA
2. High levels of acetyl-CoA inhibits pyruvate hydrogenase (PDH) which prevents pyruvate conversion to acetyl-CoA and stalls glycolysis
3. Excess citrate moving into the cytoplasm inhibits GLUT 4 which suppresses glucose transport
   ***FFA-derived acetyl-CoA and citrate inhibits PDH and GLUT4 to prevent glucose import and breakdown

Question 15

How does excess glucose (high sugar diet) block lipid metabolism?

Answer 15

1. Ingest glucose Pyruvate becomes acetyl-CoA  citrate… The excess citrate exits the mitochondria and enters the cytoplasm
2. The high glucose and insulin release stimulates malonyl-CoA synthesis
3. Malonyl-CoA inhibits CPT-1 which stalls the FFA attachment to carnitine (transport).
   **Glucose-derived malonyl-CoA suppressed fatty acid oxidation by inhibiting fatty acid activation via CPT-1

Question 16

3 Key shared molecules of the Randle cycle

Answer 16

Malonyl-CoA inhibits CPT-1
- From glucose - inhibits fat
- From fat - negative feedback of FFA
Citrate inhibits GLUT 4
- From glucose -negative feedback
- From fat - inhibits glucose metabolism
Acetyl-CoA - inhibits PDH
- From glucose - negative feedback
- From fat - inhibits glucose metabolism

Question 17

Obesity effects on Randle Cycle

Answer 17

Obese individuals have increased circulatory FFA. An increased use of FFA inhibits glucose metabolism via acetyl-CoA/pyruvate dehydrogenase and Citrate/GLUT 4.

This inhibition results in impaired skeletal muscle uptake after a meal (hyperglycemia) and the body producing more insulin than normal to try and balance out blood glucose level (hyperinsulinemia). Need more time and insulin to outcompete excess FFA to normalize the glucose, but this overproduction of insulin overtime can lead to insulin resistance and eventually diabetes.