Energy Balance and Obesity - Watford 2/18/16

Question 1

energy: uses and source in the body

Answer 1

• 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

Question 2

track energy in food to its “end” fx in body

Answer 2

• 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

Question 3

energy balance eqn

[variant: during weight maintenance]

Answer 3

energy in - energy out = energy stored

during wt maintain:

energy in = energy out

Question 4

imbalances in Ein and Eout don’t necessarily lead to massive continued weight gain.

why?

Answer 4

weight gain is accompanied by lean mass gain → increased metabolic rate

• new equilibrium: higher Ein = higher Eout

Question 5

Atwater table values

Answer 5

carbs: 4 kcal/g
proteins: 4 kcal/g [really 5.4, but 1.4 is urea
fats: 9 kcal/g

Question 6

digestible energy

vs

metabolizable energy

Answer 6

digestible = energy in food - energy in feces

metabolizable = energy in food - losses in feces, urine, sweat, etc

Question 7

ATP equivalents

and

reducing equivalents

Answer 7

creatine phosphate, GTP

and

NADH, NADPH, FADH₂

Question 8

what tasks does energy perform in the body?

Answer 8

• 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

Question 9

describe composition and metabolic contribution of adipose tissue vs. lean mass

Answer 9

• 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”

Question 10

breakdown of body weight

Answer 10

• body weight = fat + fat free mass
  
  • fat free mass: lean tissues + glycogen (1-2%)
  • lean tissues: 20% protein + 73% water + 7% bone

Question 11

ways to calculate body composition and body fat

Answer 11

• % 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

Question 12

common ways to assess body mass

Answer 12

• BMI, CT (high radiation), dexa (low radiation),
• skin fold thickness
• waist circumference; waist-to-hip ratio
• body plethysmography
• bioimpedance

Question 13

history of theories of energy expenditure

Answer 13

• 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)

Question 14

direct calorimetry

vs

indirect calorimetry

Answer 14

• direct calorimetry: measure of heat production
  
  • “direct” measure of egy expenditure
    
    • requires a closed system for approx 23 hr/day

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)
    *

Question 15

respiratory quotient

Answer 15

RQ, ratio of carbon dioxide produced by consumption of a fuel to oxygen used to burn that fuel

Question 16

RQ during fat synthesis

Answer 16

synthesizing fat from glucose, RQ = 2.75

RQ >= 1.1 indicates fat synthesis

Question 17

downside/inaccuracy of calorimetry

alternatives??

Answer 17

• issues with accuracy
• restrictions in movement (that aren’t realistic)
• observation (likely to change behavior)

alternative: doubly labeled water!!!

Question 18

doubly labeled water

Answer 18

• 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

Question 19

determinants of resting metabolic rate

(non-variable and variable)

Answer 19

• fixed
  
  • ​age
  • gender
  • genes
• variable
  
  • ​diet
  • FFM (fat free mass; lean body mass)
  • environmental temp
  • hormones (TH, SNS catecholamines)
  • drugs
  • stress

Question 20

determinants of thermic effect of food (TEF)

Answer 20

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

Question 21

types of factors that affect food intake

Answer 21

orexigenic: increase food intake

anorexigenic: decrease food intake

Question 22

short term and long term biological signals of levels of food intake

Answer 22

• 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)

Question 23

describe some adiposity/blood glucose signals and their sources

Answer 23

• 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

Question 24

orexigenic signals

Answer 24

1. Ghrelin
2. orexin
3. galanin
4. MCH [melanin concentrating hormone]
5. GABA [gamma amino butyric acid]
6. PYY, NPY [neuropeptide Y]

Question 25

anorexigenic signals

Answer 25

1. gastric distention 2. CCK [chelocystikinin] 3. GLP-1 [glucagon like peptide 1; type of incretin] 4. insulin 5. leptin 6. lipids, proteins/a.a.s/glucose

Question 26

how do signals from adipose tissue set off catabolic pathways?

Answer 26

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

Question 27

how do orexigenic signals set off anabolic pathways?

Answer 27

Ghrelin/orexins set off **anabolic MCH and Orexin pathways in lateral hypothalamus** ## Footnote _increase appetite, signal body to eat more_

Question 28

obesity: genetic drivers predictors/risk factors for weight gain [Pima Indian study]

Answer 28

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

Question 29

ob db experiment and implications

Answer 29

**parabiosis**: linked circulation of two mice (one obese and one not) and waited to see what happened 1. _ob/ob-wt_: ob lost weight 2. _db/db-wt_: db gained weight and wt died of starvation 3. _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

Question 30

leptin resistance

Answer 30

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)**

Question 31

Dutch famine of Winter 1944-45

Answer 31

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

Question 32

putative contributors to obesity

Answer 32

* sleep deprivation * smoking cessation * ambient temp * pharma influences * environmental pollutants (endocrine disruptors) * animal hormones/antibiotics * changes in food intake

Question 33

microbiota/obesity experiment

Answer 33

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

Question 34

brown adipose tissue

Answer 34

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

Question 35

brown vs beige vs white adipose tissue

Answer 35

**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_

Question 36

metabolic syndrome

Answer 36

* impaired glucose tolerance/insulin resistance * dyslipidemia * android obesity * HTN