Flashcards in Nutrition, Vits/Mins, Obesity Deck (87):
What is the resting energy expenditure (REE)?
1) for men, 900+10w (w=weight in kg)
2) for women, 700+7w
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)
How do you calculate BMI and what are the classes of BMI?
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)
What are the pros and cons of using BMI? What can be used instead?
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
What's the problem with fructose?
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
Describe the glycemic index
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
How do you calculate weight loss?
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
What are trans-fats and why are they the devil?
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!)
What's the deal with saturated fats?
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
What about omega-3 fatty acids? (omega-3 PUFA)
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)
What was the basis for omega-3 being healthy?
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
What are macronutrients and micronutrients?
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)
What are vitamins? What are the needed amounts?
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)
What are the classes of vitamins?
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)
What is vitamin A used for?
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
What foods have vitamin A? What are deficiency symptoms?
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)
What does vitamin D do? Which foods have vitamin D?
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.)
What are the symptoms of vitamin D deficiency? Can vitamin D toxicity occur?
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)
What does vitamin K do? What foods are a good source?
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
What does vitamin K deficiency look like?
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
What does vitamin E do? What foods are good sources?
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
What does vit E deficiency cause?
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
What does vitamin C do? What foods are a good source?
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
What does vit C deficiency cause? Who's at risk?
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
What are the energy-releasing B vitamins?
1) thiamine (B1)
2) riboflavin (B2)
3) niacin (B3)
4) pantothenic acid (B5)
6) pyridoxine (B6)
What are the hematopoietic B vitamins?
1) folate (B9)
2) cobalamin (B12)
What are the common effects of deficiencies in energy-releasing B vitamins?
1) symptoms first appear in rapidly-dividing tissues; skin (dermatitis), swollen red tongue, glossitis, GI/diarrhea
2) nervous system: peripheral neuropathy, confusion, malaise
What does thiamine do? What are good sources?
1) required cofactor for energy metabolism rxns (TPP precursor)
2) yeasts, liver, whole grains, beans/pork/fish
What does thiamine deficiency look like?
1) GI symptoms, depression, fatigue (mild)
2) Wernicke-Korsakoff (alcoholics, moderate)
3) beriberi (severe)
What does riboflavin do? What are good sources?
1) precursor of FAD/FMN
2) milk, yogurt, cheese, meat, eggs, broccoli, asparagus, oranges, whole grains
What does B2 deficiency do?
1) ariboflavinosis (rash around nose), inflamm of mouth/tongue, burning/itchy eyes, light sensitivity
2) very uncommon, but can occur in alcoholics
What does niacin do? What are good sources? What does B3 deficiency look like?
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
What does biotin do? What's a good source? What is the deficiency like?
1) coenzyme for many carboxylases
2) in many foods, intestinal bacteria can make it
3) raw egg whites snatch it up-->deficiency (RARE)
What does pantothenic acid do? What's a good source? What are deficiency symptoms?
1) needed for synthesis of CoA***
2) found in many foods, deficiencies are really rare--symptoms look like other B vit symptoms
What does pyroxidine do? What are good sources? What does deficiency look like?
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
What does folate do? What happens in folate deficiency?
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
What does cobalamin do? What are good sources?
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
What does cobalamin deficiency do?
1) pernicious anemia (megaloblastic)
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***
What are the macrominerals?
What are the microminerals?
What does calcium do? Where does it come from?
1) comes exclusively from diet**
2) major bone component
3) signaling, muscle contraction, neurotransmission
What does calcium deficiency do?
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
What does magnesium do? What does a deficiency look like?
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
What does phosphorus do? What does a deficiency look like?
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
What does iron do? What does a deficiency look like?
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***
How is iron regulated in body?
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
What happens in microcytic/hypochromic anemia?
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
What happens in iron toxicity? (can catalyze production of reactive oxygen species)
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)
What does copper do? What does a deficiency look like?
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
What are the genetic diseases of Cu metabolism?
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**
What does Zn do? What does Zn deficiency look like?
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
What does chromium do? What does a deficiency look like?
1) part of chromodulin, which helps insulin bind to its receptor
2) deficiency impairs glucose tolerance (reduces insulin effectiveness)
What does iodine do? What does deficiency cause?
1) part of T3/T4
2) causes goiter, hypo/hyperthyroidism
3) saltwater fish a great source
What does selenium do?
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
What are the other minerals?
1) manganese--superoxide dismutase, pyruvate carboxylase
2) fluoride--strengthen bones/teeth
3) boron--bone formation
4) sulfur--amino acids
What are the general population deficiencies?
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
What is obesity an independent risk factor for?
1) developing type II DM
3) joint disease, gallbladder disease, reproductive disorders, obstructive sleep apnea, some types of cancer
What causes obesity?
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 (???)
What is the 'lipostat'/'adipostat' hypothesis?
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
Can the lipostat be altered?
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)
What are ob/ob mice like? Db/Db?
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
What are the orexigenic factors?
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
What are the anorexigenic factors?
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
How does failure to regulate leptin cause obesity?
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
What are the 3 controls of body mass?
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)
How are beige adipocytes made?
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
How does UCP1/uncoupling proteins work?
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***
How is UCP1 transcription regulated?
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
What anti-obesity drugs are available?
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
What's metabolic syndrome (MetS)?
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
What are 2 theories about how visceral obesity causes metabolic syndrome?
1) NEFA increase, which inhibits insulin signaling in muscle/liver
2) adipose tissue increases cytokines, causes inflam, which then impairs insulin signaling
What are the 3 tissues affected by metabolic syndrome? (believed to be caused by something released from adipocytes)
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
Who are the bad guys released from adipose tissue?
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)
How do leptin and adiponectin (released from adipocytes) act in skeletal muscle?
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)
How does DAG work in all this?
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
What are the 5 main causes of DAG accumulation? (also, rate of FA delivery to tissue exceeds rates of intracellular beta ox)
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
How does AMPK (AMP-activated protein kinase) modulate FA beta ox?
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)
How does adiponectin affect metabolism?
1) decreases insulin resistance
2) decreases blood NEFA
3) decreases TG in liver
4) stimulates AMPK
What does reduced AMPK lead to?
1) reduced beta ox
2) DAG over-accumulation
3) insulin resistance
How does Metformin work?
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)
Which macronutrients contribute to metabolic syndrome?
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
Why is visceral fat evil?
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
What are the main mechanisms used to treat metabolic syndrome?
1) activation of AMPK
2) reduction of mitochondrial damage
3) decreasing visceral fat
4) decreasing alcohol/fructose consumption
How do the PPAR-targeted drugs work?
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
How does PPAR alpha work?
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
How does PPAR gamma work?
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*
How do weight loss and exercise counteract metabolic syndrome?
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