Week 1: Energy and Organic Matter Balance-Obesity

Question 1

Obesity and fuel composition

Answer 1

• obesity arises if body fails to properly adjust the composition of fuel the body burns in response to the composition of fuel ingested from food
• If relative amount of fat the body burns is less than relative amount in the food, then an increase in relative body fat content may result

Question 2

RQ and FQ and obesity

Answer 2

• RQ: amount of CO2 produced divided by amount of O2 consumed for living organisms
• FQ: for organic matter absorbed from food
• for fat RQ=0.7, for carbs RQ=1.0
• when RQ>FQ can lead to obesity. Indicates fat content of ingested food exceeded fat content of metabolized food

Question 3

Absorptive state characteristics

Answer 3

1. Carb, mainly glucose and fructose, as major source of energy for all cells. RQ approaches 1
2. Net synthesis of protein from amino acids
3. Net storage of glycogen in liver and muscle
4. Net storage of TG, particular in adipose tissue
   - glycerol-3-P not glycerol is source of glycerol in TG. Carbs that undergo kerb cycle is source of glycerol-3-P
   - adipocytes lack glycerol kinase
5. Conversion of amino acids and carb into FAs
   - anaerobic glycolysis of carbs can increase relative fat content of organism

Question 4

Characteristics of post absorptive state

Answer 4

1. utilization of FAs as major energy source; spared combustion of glucose. Except in nervous tissue and RBCs which still use glucose.
   - Increased circulating levels of FA acts on muscle to decrease glucose utilization. RQ approaches 0.8
2. Net release of FAs from adipose tissue
3. Maintenance of blood glucose levels via hepatic glucose production
   - gluconeogenesis and glycogenolysis
4. Net protein degradation with hepatic conversion of amino acids to glucose

Question 5

Starvation state

Answer 5

-after utilizing glycogen stores in liver and gluconeogenesis from lactate or amino acids from muscle, nervous tissue starts using ketoacids from fat

Question 6

Insulin and absorptive state

Answer 6

1. promotes glucose uptake into muscle. Glucose is phosphorylated once it enters muscle, and can’t leave b/c muscle lacks Glucose-6-phosphatase
   - promotes muscle combustion of CHO and reduces utilization of fat
2. Promotes glycogen accumulation, mainly in muscle and fat, but also liver
3. Promotes amino acid uptake and protein accumulation, particularly in muscle. Reservoir of AAs for later conversion to glucose by liver
4. promotes TG storage in adipose tissue
   - glucose into adipocytes, supplies glycerol-3-P
   - insulin promotes dephophorylation and deactivation of HSL (hormone sensitive lipase)
   - promotes fat accumulation
5. decreases glucagon release

Question 7

Insulin regulation: promoters

Answer 7

STIMULATES INSULIN RELEASE

• food ingestion, vagal neurons promote insulin release
• incretins released from gut (distinguishes rise of glucose from hepatic glucose output in fight or flight response)
• GLP1: lowers blood glucose by increase insulin release, suppresses glucagon
• DPP-4 inhibitors inhibit degradation of GLP-1

Question 8

Insulin regulation: Inhibition of secretion

Answer 8

• somatostatin produced by pancreas

- sympathetic control: Norepinephrine and epinephrine act via a-adrenergic receptors, inhibit insulin release

Question 9

hyperinsulinemia and obesity

Answer 9

• hypothesis: hyperinsulinemia is a cause of obesity
• insulin secretion is pulsatile, pulses are greater in the obese
• insulin resistance: obese persons need greater amounts of insulin for effects

Question 10

Tissue selective regulation of insulin effectiveness

Answer 10

• amylin (found in amyloid deposits in pancrease of type 2 DM): inhibited insulin stimulated glucose uptake and glycogen deposition in muscle
• idea: an amylin inhibitor might potentiate insulin action on muscle but not fat, could decrease insulin levels and decrease adipose mass
• exercise actually does that: makes muscle uptake of glucose more insulin sensitive, possibly due depletion of muscle glycogen stores. Exercise shifts fuel utilization at a rest toward fat oxidation

Question 11

Glucagon and post-absorptive state

Answer 11

• fall in glucose is main stimulus of release of glucagon. Opposes action of insulin on liver and fat
  1. promotes release of fatty acids from adipose tissue
• increase cAMP and promotes phosphorylation of HSL. TGs broken down to FAs
• flow of FAs to muscle decreases combustion of glucose
  2. promotes release of glucose from liver
• glucagon increases phosphorylation of glycogen synthase and phosphorylase
• glycogenolysis and glucose release

Question 12

Epinephrine and post absorptive state

Answer 12

1. promotes release of FA from adipose tissue
2. Promotes release of glucose from liver
3. acts on muscle to decrease insulin action, promotes glycogenolysis and lactate efflux
4. promotes glycogen and inhibits insulin release
5. promotes blood flow through adipose tissue, lipolysis, and FA efflux

Question 13

CNS and regulation of energy and organic matter balance

Answer 13

• lesions to lateral hypothalamus: cause anorexia and adipose wasting
• lesions to VMH: cause overeating and obesity
• ob/ob mice: leptin deficient. Obese
• db/db and Zucker rat: obese, high leptin, dysfunctional leptin receptor
• leptin: inhibits glucagon release

Question 14

Gut as neuroendocrine organ

Answer 14

• distension and composition of food cause signals to brain and other organs to regulate eating behavior
• GPCRs in mouth coupled to G protein to provide taste. Also found in gut, regulate release of GLP-1 from gut.
• ghrelin: hormone from gut, “hunger hormone”

Question 15

Thermogenesis form oxidation uncoupled from activity

Answer 15

• in brown adipose tissue (BAT), found uncoupling protein (UCP) that uncouples oxidation from generation of ATP. Oxidation produces heat.
• mild cold exposure increases human BAT glucose consumption. Agents that mimic cold activation BAT thermogenesis my be Rx for obesity
• hypothesis: tissues other than white adipose tissue, such as muscle and BAT, may produce endocrine signals indicating status of their energy reservoir and that aberrations involving them may contribute to obesity

Question 16

Adipocyte progenitor cells, angiogenesis

Answer 16

• bone derived progenitor cells may be a source of adipocytes and vasculature cells for the expansion of adipose tissue and its vasculature
• possible therapeutic target for treating some obesities