Biochemical Basis Of Energy Homeostasis

Question 1

What is the general/average energy expenditure in humans

Answer 1

10% = thermic effect of food

• energy spent digesting food and absorbing nutrients
• 210 kcal

30% = physical activity

• most variable*
• roughly 630 kcal

60% = resting energy expenditure/ BMR

• least variable*
• 1300 kcal

Total = roughly 2150 kcal

Question 2

Kcal/g of each major macronutrient and their respiratory quotient

Answer 2

Carbohydrate = 4 kcal/g
- RQ = 1.0

Protein = 4 kcal/g
- RQ = 0.84

Fat = 9 kcal/g
- RQ = 0.71

**alcohol = 7kcal/g (not a major macro)

• *RQ = amount of CO2 released/amount of CO2 absorbed. **
• important in respiratory disease patients, since the more CO2 they release (high RQ diet), the more they exacerbate their condition

Question 3

Difference between basal metabolic rate (BMR) and resting metabolic rate (RMR)

Answer 3

BMR = energy expenditure of a person mentality and bodily at rest in a thermoneutral environment 12-18hrs after a meal

• requires fasting and sleep for at least 8 hrs to measure
• is more accurate measurement of the metabolic rate

RMR = less strict and no fasting required

• energy required to maintain life
• doesn’t require fasting and sleep for 8 hrs to measure
• is less accurate measurement of the metabolic rate

Question 4

What is the split of BMR calories used in each organ system?

Answer 4

27% = liver

19% = Brain
- this NEVER changes under any condition

18% = skeletal muscles

10% = kidney

7% = heart

19% = everything else

Question 5

What factors affect BMR?

Answer 5

Gender
- males have higher BMR

Body temperature
- hotter internal temp causes higher BMR

Environmental temperature
- high BMR in cold

Thyroid status
- hyperthyroidism increases this

Pregnancy and lactation
- increases this

Age
- younger increases; older decreases

Body composition
- increased with higher muscle mass

Question 6

What are the 4 major factors that regulate body weight

Answer 6

1) genetics/epigenetics
2) environmental factors
3) behavioral factors
4) physiological factors

all affect metabolic adaptation

Question 7

What is the body weight “set-point” model?

Answer 7

States that each individual has a biological predetermined “set-point” for body weight
- the set point is always returned to

This set point is defined as

• adipose stores are added when body weight falls below the set point (under feeding)
• adipose stores are utilized when the body weight rises above the set point (over feeding)

this is a flawed model since it doesnt explain a lot of things such as obesity, metabolic adaptations, gradual increase of body weight with age, etc.

Question 8

Long-term and short term afferent signals for body weight and hunger

Answer 8

GI tract = ghrelin

adipose = leptin

Pancreas = insulin/glucagon

all go to the hypothalamus to release efferent signals

Question 9

Efferent signals that regulate hunger and appetite

Answer 9

Proopiomelanocortin -> MSH
- promotes catabolic or energy burning

Neuropeptide Y. Agouti-related peptide
- promotes anabolic or energy consumption

both go to the brainstem satiety center -> hypothalamus

Question 10

Hedonic system of regulation of body weight

Answer 10

Visual/olfactory/smell triggers that activate orexigenix or anorexigenix pathways

can override the homeostatic system with Afferent and efferent signals

Question 11

What are the three types of adipose tissue?

Answer 11

White = generalized fat

• widely dispersed in humans
• is an active endocrine organ
• is visceral fat
• derived from PPARy/RXR signaling to perivascular stem cells

Beige = sub population of white fat that has mild thermoregulation features of brown fat
- found in adult humans but not in infants

Brown = primary thermogenesis in infants

• is found around the scapula and is only in infants
• derived from PRDM16/PGC-1 signaling to skeletal myogenic progenitor cells

white fat can undergo “browning” where it transdifferentiates into brown fat

Question 12

How does increased energy intake (excess eating) change white adipose tissues?

Answer 12

Increases in size and number = obesity
- once WAT has reached its max size they undergo recruitment and proliferation of new preadipocytes

weight loss = decrease in size only NOT number

Question 13

Leptin signaling pathways

Answer 13

1) leptin (167 AA peptide) binds to JAK2 kinase receptor
- these receptors are expressed in adipose, heart, muscle, lung, small intestine, liver and hypothalamus (most is hypothalamus)

2) binding activates SHP-2 and STAT3 proteins
- SHP-2 = upregulates MAPK which both increases energy homeostasis as well as agonizes STAT 3
- STAT 3 = upregulates gene transcription of energy homeostasis (multiple proteins) and feedback inhibition (SOCS-3/PTP1B)

Leptin receptors are found in adipose, heart, muscle, lungs, small intestine, liver and hypothalamus

Question 14

Leptin deficiency and leptin receptor deficiency

Answer 14

Leptin deficiency = ob(Lep) gene mutation

Leptin receptor deficiency = db(LepR) gene mutation
- are both rare mutations in humans that cause obesity by inducing hyperphagia (increased appetite and hunger)

can also show leptin resistance where there is normal levels of leptin but insensitivity to the regulating effects of the hormone = also results in obesity

Question 15

Adioponectin signaling pathway

Answer 15

1) Adiponectin (223-AA peptide) binds to adipo R1/R2 receptors
2) upregulates ceramide molecules and ceramide activity which promotes glucose uptake and sphingomyelin production

3) also produces APPL1 proteins which bind to insulin receptors (1 and 2) which hyper stimulates these receptors
- makes them more sensitive to insulin

• *endocrine effects of adiponectin**
• insulin sensitized
• suppresses inflammation
• anti-apoptotic effects
• mitigates oxidative stress