Energy Balance and Obesity - Watford 2/18/16 Flashcards
energy: uses and source in the body
- biological work in the body (kinetic energy)
- mechanical energy (m contraction)
- chemical
- osmotic
- electrical
- energy sourced from food (potential energy)
- metabolize fat, carbs, proteins
- allows for proton gradient and ATP synth
- HEAT
track energy in food to its “end” fx in body
- food energy
- lose 1-9%
- lose some more in sweat, urine, sloughed off cells
- ultimately end up with metabolizable energy
-
metabolizable energy has 3 fates
- 50% lost as heat (inefficient)
- 5-10% lost as cost of digestion/abs/storage
- 25-40% stored in high energy ATP bonds
energy balance eqn
[variant: during weight maintenance]
energy in - energy out = energy stored
during wt maintain:
energy in = energy out
imbalances in Ein and Eout don’t necessarily lead to massive continued weight gain.
why?
weight gain is accompanied by lean mass gain → increased metabolic rate
- new equilibrium: higher Ein = higher Eout
Atwater table values
carbs: 4 kcal/g
proteins: 4 kcal/g [really 5.4, but 1.4 is urea
fats: 9 kcal/g
digestible energy
vs
metabolizable energy
digestible = energy in food - energy in feces
metabolizable = energy in food - losses in feces, urine, sweat, etc
ATP equivalents
and
reducing equivalents
creatine phosphate, GTP
and
NADH, NADPH, FADH2
what tasks does energy perform in the body?
- pumps: Na/K ATPase (20-40% of basal egy expenditure), other transport pumps
- thermic effect of food: 5-10%
- inefficiency/heat: 50%
- synthesis, needed to maintain life: 20-40%
activity causes variations in expenditure
describe composition and metabolic contribution of adipose tissue vs. lean mass
-
adipose tissue: metabolically inactive (relatively)
- 85% lipid, 15% water
-
lean mass: where metabolism occurs
- 20% protein, 80% water
most energy expenditure occurs in lean body mass or “fat free mass”
breakdown of body weight
- body weight = fat + fat free mass
- fat free mass: lean tissues + glycogen (1-2%)
- lean tissues: 20% protein + 73% water + 7% bone
ways to calculate body composition and body fat
- % fat vs % lean
- bioimpedance analysis
- hydrodensitometry
- 2 compartment models: fat, fat-free mass
- 4 compartment models
- BW = water + protein + bone mineral + fat(+ glycogen - no way to measure)
- BW = BCM (body cell mass) + fat + skeleton + ecf
common ways to assess body mass
- BMI, CT (high radiation), dexa (low radiation),
- skin fold thickness
- waist circumference; waist-to-hip ratio
- body plethysmography
- bioimpedance
history of theories of energy expenditure
- Santorio: weight himself, food intake, excretion for 30 years
- “insensible perspiration”
- Lavoisier: father of modern chem/nutrition
- invented indirect calorimetry too
energy expenditure = thermogenesis
or
energy expenditure = oxygen consumption (ATP production)
direct calorimetry
vs
indirect calorimetry
-
direct calorimetry: measure of heat production
- “direct” measure of egy expenditure
- requires a closed system for approx 23 hr/day
- “direct” measure of egy expenditure
inconvenient, usually foregone for indirect calorimetry
-
indirect calorimetry: measures oxygen consumption via respiratory quotient RQ
- RQ = CO2 produced/O2 consumed
- 1 = carbs, .7 = fats, in between = mixture
- instead of lumping all expenditure over a day, allows for assessing individual components of expenditure (rest, activity, after meals)
*
- RQ = CO2 produced/O2 consumed
respiratory quotient
RQ, ratio of carbon dioxide produced by consumption of a fuel to oxygen used to burn that fuel
RQ during fat synthesis
synthesizing fat from glucose, RQ = 2.75
RQ >= 1.1 indicates fat synthesis
downside/inaccuracy of calorimetry
alternatives??
- issues with accuracy
- restrictions in movement (that aren’t realistic)
- observation (likely to change behavior)
alternative: doubly labeled water!!!
doubly labeled water
- assessment of total free-living energy expenditure
water composed of “heavy” isotopes of H and O
2H218O
excretion of H has to be through water (urine, sweat, etc)
excretion of O can be either water or CO2
- since H and O are lost at different rates due to metabolism, ratio of H to O can give you metabolic rate
determinants of resting metabolic rate
(non-variable and variable)
-
fixed
- age
- gender
- genes
-
variable
- diet
- FFM (fat free mass; lean body mass)
- environmental temp
- hormones (TH, SNS catecholamines)
- drugs
- stress
determinants of thermic effect of food (TEF)
aka diet induced thermogenesis, specific dynamic action
= rise in RMR 2-5h after a meal
- varies by type of macronutrient ingested
- approx 25-40% of protein calories lost in this window
- 6-8% carb calories lost
- 3% fat calories lost
- differences may be due to variable energy cost of storing different nutrients
types of factors that affect food intake
orexigenic: increase food intake
anorexigenic: decrease food intake
short term and long term biological signals of levels of food intake
-
long term
- insulin and leptin levels reflect body fat
-
short term
- signals from gut: Ghrelin, CCK, GLP-1 (glucagon like peptide 1), PYY, apoA IV
- leptin modulates sensitivity to these short term signals (like CCK)
- signals from gut: Ghrelin, CCK, GLP-1 (glucagon like peptide 1), PYY, apoA IV
describe some adiposity/blood glucose signals and their sources
- satiation signals
- CCK, GLP-1, gastric distention [liver, GI tract]
- adiposity signals
- leptin [fat]
- insulin [pancreas]
- nutrients
signal the brain via ARCTUATE NUCLEUS re: food intake and energy expenditure
orexigenic signals
- Ghrelin
- orexin
- galanin
- MCH [melanin concentrating hormone]
- GABA [gamma amino butyric acid]
- PYY, NPY [neuropeptide Y]
anorexigenic signals
- gastric distention
- CCK [chelocystikinin]
- GLP-1 [glucagon like peptide 1; type of incretin]
- insulin
- leptin
- lipids, proteins/a.a.s/glucose
how do signals from adipose tissue set off catabolic pathways?
adipose tissue produces leptin, which stimulates catabolic MC4R pathway in ventromedial hypothalamus
- leptin stimulates POMC: activates MC4R pathway
- activate activator
- leptin inhibits Agouti-related peptide (AgRP/NPY neurons): inhibit an inhibitor of MC4r
- inhibit inhibitor
how do orexigenic signals set off anabolic pathways?
Ghrelin/orexins set off anabolic MCH and Orexin pathways in lateral hypothalamus
increase appetite, signal body to eat more
obesity: genetic drivers
predictors/risk factors for weight gain [Pima Indian study]
most human obesities likely polygenic
- complicated interactions of multiple genes
-
risk factors [Pima]
- low RMR/body temp
- high RQ
- high insulin sensitivity
- low spontaneous physical activity
ob db experiment and implications
parabiosis: linked circulation of two mice (one obese and one not) and waited to see what happened
- ob/ob-wt: ob lost weight
- db/db-wt: db gained weight and wt died of starvation
- ob/ob-db/db: db gained weight, ob died of starvation
leptin is produced by brain: signals to increase egy expenditure, decrease food intake
- ob has no leptin, which is why parabiosis with a wt gave it leptin and it lost weight
- db has faulty leptin receptors, which is why parabiosis made no change: continuous eating/weight gain
coming full circle…
- ob-db parabiosis leads to a MASSIVE flux of leptin from db (built up due to bad receptor) to the ob, leading it to stop eating and starve to death
leptin resistance
seen in many obese human beings
- causes
- leptin receptor polymorphisms
- defects in leptin-R signalling?
regardless, serum leptin levels are increased in proportion to body fat in most obese people (hyperleptinemia)
Dutch famine of Winter 1944-45
followup 50 years later of kids in utero during famine years saw increased
- obesity
- diabetes/insulin resistance
- heart disease
worse outcomes seen when famine hit during early stages of gestation
fetal programming/metabolic programming/fetal origins of chronic disease/Barker hypothesis
- changes to histones and DNA methylation during catch-up period of growth after an in utero insult makes you more susceptible to chronic disease like DM2
putative contributors to obesity
- sleep deprivation
- smoking cessation
- ambient temp
- pharma influences
- environmental pollutants (endocrine disruptors)
- animal hormones/antibiotics
- changes in food intake
microbiota/obesity experiment
took feces from identical twins (one lean, one obese) and transplated into germ-free mice
- both had same caloric intake, but began to take on lean/obese phenotype depending on which feces they got
later took obese and lean mice and put them together in same cage (mice are coprophagic - eat each others feces)
- obese mice housed with lean mice dropped weight and their microbiota switched over
- germ free mice housed with both obese and lean mice because lean
brown adipose tissue
BAT has UCP 1 (uncoupling protein 1), which dissipates the proton gradient
- brings protons back into mitochondria without generating ATP
- generate a TON of heat
BAT functions as thermogenic tissue (many mitochondria, many lipid droplets, highly vascularized) - newborns, hibernation
brown vs beige vs white adipose tissue
brown: dermomyotomal precursors: myogenic factor 5 (Mycf5) present - not present in others
beige (brown in white): mesodermal precursors
white: mesodermal precursors
beige and white might be able to be converted to one another
metabolic syndrome
- impaired glucose tolerance/insulin resistance
- dyslipidemia
- android obesity
- HTN
