Nutrition, Vits/Mins, Obesity

Question 1

What is the resting energy expenditure (REE)?

Answer 1

1) for men, 900+10w (w=weight in kg)
2) for women, 700+7w
3) sedentary=1.2
4) moderately active=1.4
5) very active=1.8
6) balancing this keeps a person in energy balance (but true values vary based on person)

Question 2

How do you calculate BMI and what are the classes of BMI?

Answer 2

1) BMI=weight in kg/square of height in meters (kg/m^2)
2) <18.5-underweight, 18.5-24.9-normal
3) 25-29.9-Grade 1 overweight (just overweight), 30-39.9-grade 2 overweight (obese)
4) 40.0-grade 3 overweight (morbidly obese)

Question 3

What are the pros and cons of using BMI? What can be used instead?

Answer 3

1) EASY TO CALCULATE!
2) correlates with disease
3) good at measuring relative risk of diseases (type II DM, etc.)
4) however, hard to determine what’s fat and what’s lean mass
5) had to separate upper body fat and lower body fat
6) waist-height ratio much better at determining risk

Question 4

What’s the problem with fructose?

Answer 4

1) metabolized primarily in liver (different general path from glucose)
2) when liver has too much fructose, it turns it into TGs that stay in liver (hepatic steatosis)
3) this can cause other problems, like insulin resistance and metabolic problems

Question 5

Describe the glycemic index

Answer 5

1) it measures the extent to which blood glucose rises after ingestion
2) the higher the glycemic index, the greater the insulin spike
3) the greater the insulin spike, the likelier postprandial insulinemia is going to be harmful; “wear out” the pancreas and cause type II DM
4) whole grains/slowly digested carbs have a lower glycemic index, cause lower levels of insulin spike

Question 6

How do you calculate weight loss?

Answer 6

1) assume all weight loss is adipose tissue (sort of…), which is 85% fat and 15% H2O
2) 1kg adipose=850g fat
3) 850g fat x 9 kcal/g=7650 kcal/kg adipose tissue lost
4) proteins/carbs have 4 cal/g, fats have 9cal/g, alcohol 7cal/g
5) 1 kcal=4.2 kJ, 1 Watt=1 J/s=60 J/min=0.06 kJ/min

Question 7

What are trans-fats and why are they the devil?

Answer 7

1) PUFA+H2, catalyst–>trans-unsaturated fats
2) occurs due to the process of partially hydrogenating the PUFAS in veggie oils (margarine, etc.) to cause FAs with trans, rather than cis, double bonds
3) eating foods with trans-FA has a strong correlation with bigger risk of CAD
4) trans-fats help prolong shelf life and keep our pastries firm/margarine stiff at room temp, which is why they are used (‘merica!)

Question 8

What’s the deal with saturated fats?

Answer 8

1) as a class, they’re atherogenic
2) intake of saturated fats correlates with increased risk of CHD
3) not all are created equally though; stearic acid isn’t atherogenic

Question 9

What about omega-3 fatty acids? (omega-3 PUFA)

Answer 9

1) eating it 1-2x a week seems to lower the relative risk (RR) of CHD death
2) however, the beneficial effects of eating fish didnt correlate with the omega-3 content of the fish
3) probably had something to do with the fish protein or something about the fish eaters themselves (external factors)

Question 10

What was the basis for omega-3 being healthy?

Answer 10

1) EPA (20C) and DHA (22C) are long-chain omega-3 FAs that are precursors of eicosanoids that reduce inflamm, lessen the likelihood of platelet aggregation
2) not sure if the benefits of eating fish are due to this yet, though

Question 11

What are macronutrients and micronutrients?

Answer 11

1) macronutrients provide the bulk energy needed for a metabolic system to function
2) micronutrients provide necessary cofactors for metabolic rxns to occur
3) ‘macronutrient mix’ is a method to reduce BMI (supposedly)

Question 12

What are vitamins? What are the needed amounts?

Answer 12

1) “a diverse group of organic molecules required in very small quantities for health, growth, survival”
2) many act as co-enzymes; symptoms of deficiency come from loss of enzyme activity
3) DRI (dietary reference intakes) and RDA (recommended daily allowance)

Question 13

What are the classes of vitamins?

Answer 13

1) lipid soluble are vitamins A, D, K, E (more like lipids, deficiencies don’t arise as quickly, but toxicity can be an issue)
2) water-soluble are B and C vitamins (more hydrophilic, deficiencies arise more quickly, less likely to be toxic)

Question 14

What is vitamin A used for?

Answer 14

1) used in the visual cycle (rhodopsin and cone opsins)
2) used in synthesis of certain glycoproteins and mucopolysaccharides
3) it’s retinoic acid (Accutane!), retinol, retinal, beta-carotene, acts as hormone/anitoxidant–derivatives of all-trans retinal

Question 15

What foods have vitamin A? What are deficiency symptoms?

Answer 15

1) egg yolks, lover, butter, whole milk (retinol)
2) caretenoids in dark green/yellow veggies, carrots
3) symptoms are early night blindness, xerophthalmia (dry eye), follicular hyperkeratosis (looks like goose bumps, but doesn’t go away)

Question 16

What does vitamin D do? Which foods have vitamin D?

Answer 16

1) maintains bone
2) maintains calcium homeostasis
3) produced in skin by UV radiation (sun), converted via liver/kidneys
4) sources include saltwater fish (salmon), liver, egg yolks, certain dairy products and other foods are fortified with vitamin D2
5) may prevent some kinds of cancer (breast cancer in post-menopausal women, etc.)

Question 17

What are the symptoms of vitamin D deficiency? Can vitamin D toxicity occur?

Answer 17

1) rickets (kids), osteomalacia (adults)
2) increased risk of cancer/metabolic syndrome/DM/infection
3) too much vit D can be toxic, but research suggests that levels higher than the RDA are beneficial (prescribed, vit D3 is the usual supplemental form)

Question 18

What does vitamin K do? What foods are a good source?

Answer 18

1) helps catalyze the addition of gamma-carboxyglutamate to clotting enzymes
2) helps localize enzymes needed for blood clotting
3) green vegetables
4) has a quinone ring

Question 19

What does vitamin K deficiency look like?

Answer 19

1) easy bruising, bleeding, hemorrhage
2) newborns can lack the intestinal bacteria that make vitamin K, need supplements; in adults, long-term antibiotics can kill the intestinal bacteria that make vit K
3) Warfarin is a vit K analog, anticoagulant

Question 20

What does vitamin E do? What foods are good sources?

Answer 20

1) antioxidant, scavenges free radicals
2) protects membranes from damage, prevents oxidation of LDL
3) sources are oils, wheat germ, margarine–vit E doesn’t seem to have a toxicity

Question 21

What does vit E deficiency cause?

Answer 21

1) cardiovascular disease (can’t oxidize LDL)
2) neurological symptoms
3) bad, since vit E located in ALL cell and organelle membranes
4) people with absorptive diseases susceptible

Question 22

What does vitamin C do? What foods are a good source?

Answer 22

1) ascorbic acid is a cofactor for oxidases involved in collagen formation
2) needed for synthesis of steroids in stress response/trauma response
3) citrus, green veggies, tomatoes

Question 23

What does vit C deficiency cause? Who’s at risk?

Answer 23

1) bruising/immunocompromised when mild, scurvy (impaired wound healing, osteoporosis, hemorrhage, anemia since it helps reduce iron, fatigue, periodontal disease) when very deficient
2) smokers, poor diet; people with long-term use of aspirin, oral contraceptives, corticosteroids

Question 24

What are the energy-releasing B vitamins?

Answer 24

1) thiamine (B1)
2) riboflavin (B2)
3) niacin (B3)
4) pantothenic acid (B5)
5) biotin
6) pyridoxine (B6)

Question 25

What are the hematopoietic B vitamins?

Answer 25

1) folate (B9)

2) cobalamin (B12)

Question 26

What are the common effects of deficiencies in energy-releasing B vitamins?

Answer 26

1) symptoms first appear in rapidly-dividing tissues; skin (dermatitis), swollen red tongue, glossitis, GI/diarrhea
2) nervous system: peripheral neuropathy, confusion, malaise

Question 27

What does thiamine do? What are good sources?

Answer 27

1) required cofactor for energy metabolism rxns (TPP precursor)
2) yeasts, liver, whole grains, beans/pork/fish

Question 28

What does thiamine deficiency look like?

Answer 28

1) GI symptoms, depression, fatigue (mild)
2) Wernicke-Korsakoff (alcoholics, moderate)
3) beriberi (severe)

Question 29

What does riboflavin do? What are good sources?

Answer 29

1) precursor of FAD/FMN

2) milk, yogurt, cheese, meat, eggs, broccoli, asparagus, oranges, whole grains

Question 30

What does B2 deficiency do?

Answer 30

1) ariboflavinosis (rash around nose), inflamm of mouth/tongue, burning/itchy eyes, light sensitivity
2) very uncommon, but can occur in alcoholics

Question 31

What does niacin do? What are good sources? What does B3 deficiency look like?

Answer 31

1) precursor of NAD/NADP coenzymes in metabolism redox rxns
2) meat/high protein foods–need tryptophan, since niacin in made from it
3) 4D’s, people who eat corn/millet based diets get it

Question 32

What does biotin do? What’s a good source? What is the deficiency like?

Answer 32

1) coenzyme for many carboxylases
2) in many foods, intestinal bacteria can make it
3) raw egg whites snatch it up–>deficiency (RARE)

Question 33

What does pantothenic acid do? What’s a good source? What are deficiency symptoms?

Answer 33

1) needed for synthesis of CoA***

2) found in many foods, deficiencies are really rare–symptoms look like other B vit symptoms

Question 34

What does pyroxidine do? What are good sources? What does deficiency look like?

Answer 34

1) precursor of pyridoxyl phosphate (PLP) enzyme cofactor, needed for glycogen breakdown and synthesis of GABA/heme
2) found in meat, egg yolks, veggies, whole grains
3) deficiency is mental symptoms (mild), neuropathy/convulsions/hyperhomocysteinemia/anemia (severe)
4) people taking certain drugs (isoniazid) are susceptible

Question 35

What does folate do? What happens in folate deficiency?

Answer 35

1) converted to THF, needed for DNA synthesis
2) neural tube defects, hyperhomocysteinuria, macrocytic anemia (NOT called pernicious)
3) preggos, old alcoholics, people taking the Pill and anticonvulsants

Question 36

What does cobalamin do? What are good sources?

Answer 36

1) coenzyme in methionine synthesis, converts methmaolonyl CoA–>succinyl CoA
2) needed for folate metabolism
3) beef, fish, dairy, fortified cereals
4) veggies MIGHT be at risk for not eating beef

Question 37

What does cobalamin deficiency do?

Answer 37

1) pernicious anemia (megaloblastic)
2) demyelination
3) without B12, folate trapped in N5-methyl-THF form, can’t be reconverted into THF; causes deficiency of nucleotides, so RBCs keep getting bigger without dividing, can’t carry enough oxygen
4) pernicious anemia refers specifically to B12-deficiency from lack of intrinsic factor***

Question 38

What are the macrominerals?

Answer 38

1) potassium
2) sodium
3) chloride
4) calcium
5) phosphate
6) sulfur
7) magnesium

Question 39

What are the microminerals?

Answer 39

1) iron
2) copper
3) zinc
4) chromium
5) iodine
6) magnesium
7) selenium
8) molybdenum
9) fluroide
10) boron

Question 40

What does calcium do? Where does it come from?

Answer 40

1) comes exclusively from diet**
2) major bone component
3) signaling, muscle contraction, neurotransmission
4) coagulation

Question 41

What does calcium deficiency do?

Answer 41

1) muscle cramps, osteoporosis, rickets
2) children/women/old people
3) vit D needed for calcium absorption and utilization
4) exercise helps maintain bone density; postmenopausal women need even higher levels of calcium to keep their bone mass up

Question 42

What does magnesium do? What does a deficiency look like?

Answer 42

1) needed for enzymes using MgATP as substrate
2) highly present in bone (needed for bone formation)
3) weakness, tremors, arrythmia (neuromusuclar signs)–alcoholics, people on diuretics, with severe diarrhea/vomiting

Question 43

What does phosphorus do? What does a deficiency look like?

Answer 43

1) mostly present as phosphates
2) major component in bone; part of nucleic acids, membrane lipids, needed in all energy-producing rxns***
3) rare deficiency–rickets, muscle weakness/breakdown/seizure
4) lots of it in food

Question 44

What does iron do? What does a deficiency look like?

Answer 44

1) needed for oxygen/carbon dioxide transport in hemoglobin
2) needed for ox phos
3) cofactor in several nonheme iron proteins/cytochroms
4) microcytic hypochromic anemia, decreased immunity
5) most common nutrient deficiency in the world***

Question 45

How is iron regulated in body?

Answer 45

1) only Fe+3 can be used, regulation of reduction to Fe+2 closely regulated, reduction promoted by ascorbic acid
2) Fe+3 must be released from food, but hard to absorb (acidic pH)–why Popeye didn’t get as much Fe as he thought he did

Question 46

What happens in microcytic/hypochromic anemia?

Answer 46

1) small, pale RBCS
2) less hemoglobin made, RBCs undergo more cell divisions waiting for hemoglobin
3) symptoms are fatigue, pallor, weakness, dizziness
4) menstruating women, kids, old people at risk

Question 47

What happens in iron toxicity? (can catalyze production of reactive oxygen species)

Answer 47

1) hemochromatosis (can be genetic), body overloaded and iron deposited in many tisses–liver, pancreatic, cardiac function compromised–mitochondrial function messed up–>lactic acidosis
2) iron overdose in kids is most common toxicity, from taking too many supplements (accidentally)

Question 48

What does copper do? What does a deficiency look like?

Answer 48

1) helps iron absorption via ceruloplasmin
2) coenzyme for enzymes needed in collagen synthesis, fatty acid metabolism, eliminating ROS
3) ceruloplasmin oxidizes Fe+2–>Fe+3, helps it bind to transferrin–Cu deficiency can cause anemia
4) fragile bones, arteries, demineralization
5) taking too much Zn causes Cu deficiency since they compete for the same transporter

Question 49

What are the genetic diseases of Cu metabolism?

Answer 49

1) Menkes: mutations in Cu transporter
2) Wilson’s: mutations in Cu transporter cause Cu overload; not sequestered properly, builds up in liver causing liver/nervous system symptoms–causes brown ring around iris**

Question 50

What does Zn do? What does Zn deficiency look like?

Answer 50

1) cofactor for over 300 metalloenzymes
2) structural role in many proteins (Zn finger domains)
3) found in meat, shellfish, nuts, legumes
4) deficiency causes poor wound healing, dermatitis (characteristic scaly)**, poor growth/development in kids
5) old people/alcoholics/people with kidney/malabsorptive disease susceptible

Question 51

What does chromium do? What does a deficiency look like?

Answer 51

1) part of chromodulin, which helps insulin bind to its receptor
2) deficiency impairs glucose tolerance (reduces insulin effectiveness)

Question 52

What does iodine do? What does deficiency cause?

Answer 52

1) part of T3/T4
2) causes goiter, hypo/hyperthyroidism
3) saltwater fish a great source

Question 53

What does selenium do?

Answer 53

1) part of antioxidant enzymes (glutathione peroxidase, etc)
2) part of deiodinase enzymes in T3/T4 metabolism
3) found in seafood, muscle meat, cereals
4) deficiency rare, but cretinism and cardiomyopathy

Question 54

What are the other minerals?

Answer 54

1) manganese–superoxide dismutase, pyruvate carboxylase
2) fluoride–strengthen bones/teeth
3) boron–bone formation
4) sulfur–amino acids

Question 55

What are the general population deficiencies?

Answer 55

1) kids: iron/calcium
2) teenagers: calcium/magnesium, maybe vit A/C/B6
3) women: iron, calcium, magnesium, vit B6, folate
4) elderly: vit B6/B12, zinc and chromium
5) alcoholics: pretty much everything, but especially folate, B6, thiamine

Question 56

What is obesity an independent risk factor for?

Answer 56

1) developing type II DM
2) CVD
3) joint disease, gallbladder disease, reproductive disorders, obstructive sleep apnea, some types of cancer

Question 57

What causes obesity?

Answer 57

1) genetics: polygenic (many genes involved), they haven’t found a single “master” gene yet
2) environment: diet, exercise; these kinds of factors are MAJOR
3) differences in gut microflora (???)

Question 58

What is the ‘lipostat’/’adipostat’ hypothesis?

Answer 58

1) most people are in energy balance: energy intake and expenditure are nearly the same–weight seems to have a set point
2) involves a fat-to-brain signaling system
3) leptin (adipokine, hormone-like protein released from adipose tissue), sends signal to brain
4) leptin receptors in hypothalamus respond
5) the hypothalamus alters orexigenic (feeding) and anorexigenic (anti-feeding)
6) ideally, the brain should receive a strong signal from excess fat and lots of leptin to decrease appetite

Question 59

Can the lipostat be altered?

Answer 59

1) 15-20% is the set point for most people; however, if you exercise and decrease body fat you can increase food intake and decrease food expenditure (less leptin)
2) in an obese state, the set point can increase (30-35%) with increased leptin, where food intake still = energy expenditure–obese people develop leptin insensitivity
3) the set point of a lipostat can change during a person’s life–once a new set point made, the body will strongly keep that new set point (meaning reset lipostat in obese people defends the obese state and resists weight loss)

Question 60

What are ob/ob mice like? Db/Db?

Answer 60

1) ob/ob don’t produce leptin–act as if starved
2) when given leptin, feeding/body weight went down, energy expenditure went up–reversed once leptin gone
3) effects of leptin were anti-orexigenic and anorexigenic, double whammy to decrease feeding and increase energy expenditure
4) db/db lack leptin receptor

Question 61

What are the orexigenic factors?

Answer 61

1) made in AgRP neurons in hypothalamus
2) agouti-related protein (AgRP), neuropeptide Y (NPY), other peptides act as NTs
3) effects inhibited by leptin–increases food intake, lessens energy expenditure

Question 62

What are the anorexigenic factors?

Answer 62

1) produced by POMC neurons in hypothalamus
2) pro-opiomelanocortin (POMC), cocaine and amphetamine-regulated transcript (CART), other NTs
3) effects stimulated by leptin–lessens food intake, increases energy expenditure

Question 63

How does failure to regulate leptin cause obesity?

Answer 63

1) inadequate leptin production (RARE)
2) inappropriately low leptin secretion
3) leptin resistance, brain no longer sensitive to insulin and leptin’s effects–most common
4) chronic overnutrition may also causes hypothalamic oxidative stress on ER/mitochondrial damage–>leptin resistance and obesity

Question 64

What are the 3 controls of body mass?

Answer 64

1) CCK–sends satiety signal when food in tummy, acts indirectly on brain, short-term (meal related)
2) ghrelin–stimulates appetite when tummy empty
3) PYY-36–released in response to food by GI endocrine cells, blood levels remain high between meals (inhibits eating for up to 12 hours)

Question 65

How are beige adipocytes made?

Answer 65

1) white adipose tissue that has partially become brown adipose tissue–has increased mitochondria and UCP1 levels (uncoupler protein in brown adipose tissue, not white)
2) transition (“browning”) occurs after exercise

Question 66

How does UCP1/uncoupling proteins work?

Answer 66

1) uncoupler pokes holes in mitochondrial membrane so H+ can enter matrix; they don’t use ATP-synthase to enter, so no ATP made
2) when UCP1 used, it’s called “adaptive thermogenesis”, or “nonshivering”–energy released as heat without coupling to ATP synthesis, helps keep body temp
3) BAT (a kind of uncoupler) inversely correlates to BMI***

Question 67

How is UCP1 transcription regulated?

Answer 67

1) UCP1’s proton conductance is activated by fatty acids; when it’s cold, BAT sympathetic neurons activate beta-3 adrenergic receptors–>increased lipolysis and free FA–>UCP1 activated
2) transcr also activated by thyroid hormone receptor
3) UCP1 expression may help aid the “browning” process

Question 68

What anti-obesity drugs are available?

Answer 68

1) Qsymia/locarserin (Belviq) modulate food intake by acting on hypothalamus–side effects are a concern (increased heart rate, etc.)
2) many other drugs (ex. dinitrophenol, thyroid hormone) have been withdrawn due to serious side effects
3) no reliable, safe drug yet–diet and exercise are the best Rx

Question 69

What’s metabolic syndrome (MetS)?

Answer 69

1) also called ‘insulin resistance syndrome’ or ‘pre-diabetes’
2) pre-clinical metabolic alterations commonly associated with obesity
3) includes insulin resistance, dyslipidemia (elevated LDL, low HDL), hyperglycemia, HTN, visceral obesity
4) if any 3 of the above don’t change after 3 months of therapeutic “lifestyle” changes, then MetS it is
5) often associated with non-alcoholic hepatic steatosis, sleep apnea, male hypogonadism, female polycystic ovary syndrome

Question 70

What are 2 theories about how visceral obesity causes metabolic syndrome?

Answer 70

1) NEFA increase, which inhibits insulin signaling in muscle/liver
2) adipose tissue increases cytokines, causes inflam, which then impairs insulin signaling

Question 71

What are the 3 tissues affected by metabolic syndrome? (believed to be caused by something released from adipocytes)

Answer 71

1) skeletal muscle–organ primarily responsible for glucose disposal, glucose uptake impaired
2) liver–postprandial gluconeogenesis and glucose release (liver can’t block gluconeogenic enzymes)
3) adipose tissue–doesn’t take up glucose, increases lipolysis/releases TGs into blood, releases inflamm cytokines, doesn’t release as much adiponectin

Question 72

Who are the bad guys released from adipose tissue?

Answer 72

1) NEFA–believed that in obese people, NEFA levels exceed the rate of storage–circulating NEFA wreak havoc in muscle/liver–>lipotoxicity
2) macrophages in fat cells also release pro-inflamm cytokines that are thought to promote insulin resistance–>BAD SHIT (too much fat thought to be a stressor on body)
3) NEFA/macrophages in fat cells release ‘adipokines’, or signaling molecules (in addition to leptin)

Question 73

How do leptin and adiponectin (released from adipocytes) act in skeletal muscle?

Answer 73

1) promote beta ox and lower lipolysis
2) reduces the levels of free fatty acids and lipotoxicity
3) in contrast to leptin, adiponectin production is reduced in obesity (may help in accumulation of free FAs and insulin resistance)

Question 74

How does DAG work in all this?

Answer 74

1) DAG derived from FAs, inhibits translocation of GLUT-4 transporters to muscle cell membrane–> prevents glucose to enter cells via insulin signaling–>hyperglycemia
2) DAG also inhibits glycogen synthase and activates gluconeogenic enzymes in liver–> liver releases glucose–>hyperglycemia

Question 75

What are the 5 main causes of DAG accumulation? (also, rate of FA delivery to tissue exceeds rates of intracellular beta ox)

Answer 75

1) too many calories (increased lipid synthesis)
2) problems in adipocyte metabolism (lipid storage, lipolysis)
3) problems in mitochondria (reduced beta ox)
4) apolipoprotein C3 gene variation (reduces LPL activity)
5) reduced AMP-activated protein kinase (AMPK) signaling

Question 76

How does AMPK (AMP-activated protein kinase) modulate FA beta ox?

Answer 76

1) high AMP/ATP ratio (low energy, so ATP hydrolyzed) activates AMPK
2) adiponectin and leptin stimulate AMPK too
3) AMPK stimulates beta ox by limiting production of malonyl CoA–>malonyl no longer stops mvmt of fatty acyl CoA into mitochondria for ox, carnitine transfer no longer feedback-inhibited–>beta ox in mitochondria!
4) AMPK stimulates catabolic paths and inhibits anabolic paths–phosphorylates ACC too, inactivates it (less malonyl CoA around)

Question 77

How does adiponectin affect metabolism?

Answer 77

1) decreases insulin resistance
2) decreases blood NEFA
3) decreases TG in liver
4) stimulates AMPK

Question 78

What does reduced AMPK lead to?

Answer 78

1) reduced beta ox
2) DAG over-accumulation
3) insulin resistance

Question 79

How does Metformin work?

Answer 79

1) most commonly used to treat type II DM
2) stimulates the phosphorylation/activation of AMPK
3) enhances insulin sensitivity by decreasing hepatic glucose production (reduces fat in liver to reduce glucose output)
4) mildly inhibits mitochondrial resp. complex I activity–> decreases ATP, increases AMP/ADP–>high AMP activates AMPK
5) AMPK phosphorylates (inhibits) ACC1/ACC2–>stimulates beta ox and prevents too much FA accumulation in liver–>decreased DAG
6) smaller amounts of stored lipids–>gluconeogenesis blocked (by gene interaction and shit)

Question 80

Which macronutrients contribute to metabolic syndrome?

Answer 80

1) fructose and alcohol
2) they’re metabolized in the liver, but metabolism isn’t regulated by insulin–cannot form glycogen for storage
3) therefore, they’re highly lipogenic, causes hepatic steatosis, contribute to insulin resistance (too much fat in liver) and metabolic syndrome

Question 81

Why is visceral fat evil?

Answer 81

1) directly drains to liver (portal vein)
2) has a lot of beta-3 adrenergic receptors –> increases lipolytic response to catecholamines; however, also less responsive to insulin inhibition of lipolysis (may cause NEFA surplus into liver)
3) proinflamm molecules: may be secreted by visceral fat, inducing insulin resistance in other organs
4) tends to have many smaller fat droplets; therefore, they’re more metabolically active in lipolysis and TG synthesis

Question 82

What are the main mechanisms used to treat metabolic syndrome?

Answer 82

1) activation of AMPK
2) reduction of mitochondrial damage
3) decreasing visceral fat
4) decreasing alcohol/fructose consumption

Question 83

How do the PPAR-targeted drugs work?

Answer 83

1) fibrates–lower triglycerides and LDL, raise HDL (PPAR alpha ligands, or agonists)
2) thiazolidinediones (TZDs)–anti-diabetic and insulin-sensitizing drugs (diabetes Rx, PPAR gamma agonists)
3) PPARs themselves are ligand-activated nuclear receptors (transcr activators) that regulate genes in lipid metabolism

Question 84

How does PPAR alpha work?

Answer 84

1) works as a heterodimer with retinoid X receptors (RXR), requires cofactor
2) mainly expressed in liver (also muscle)
3) unsaturated FA are endogenous ligands, fibrates are agonists
4) upregulates beta ox, ketogenesis, gluconeogenesis

Question 85

How does PPAR gamma work?

Answer 85

1) expressed at highest levels in fat cells, also in liver/muscle–PGC-1alpha coactivator, TZD drugs are PPAR gamma ligands (agonists)
2) upregulates lipoprotein lipase, FA transporter, FA-binding protein, FA-CoA synthase–promotes insulin action and FA uptake
3) downregulates lipolysis
4) net effect is decreased circulating NEFA and increased insulin sensitivity–also upregulates adiponectin
5) **chronic TZD Rx improves glycemic control, but caloric intake/body fat increase*

Question 86

How do weight loss and exercise counteract metabolic syndrome?

Answer 86

1) exercise increases fat oxidation and reduces fat accumulation
2) exercise induces expression of PGC1-alpha, which increases mitochondrial function (improved ox phos and beta ox)–also induces secretion of irsirin (hormone); irsirin induces browning of fat tissue

Question 87

How does irsirin help fight metabolic syndrome?

Answer 87

1) makes subcutaneous white fat tissue become more like brown fat tissue
2) UPC1 expression/mitochondrial density/oxygen consumption increase–>increased energy expenditure and improved glucose homeostasis