Module 2: Obesity as a disease and the role of exercise

dyslipidemia

abnormal amount of lipids (fats) or lipoproteins in your blood

• high low-densitiy lipoprotein (LDL) - bad cholesterol

• high triglycerides

• low high-density lipoprotein (HDL) - good cholesterol

obesity leads to increased risk of

• all cause and CV disease mortality

• insulin resistance

• type 2 diabetes

• heart disease

• hypertension

• dyslipidemia

metabollically healthy obesity

describes people who have obesity but lack the usual metabolic complications, such as insulin resistance, type 2 diabetes, high blood pressure, or abnormal blood lipids

common features of metabolically healthy obesity

• fat stored mostly in subcutaneous depots rather than visceral or liver fat

• healthier, more functional adipose tissue with less macrophage infiltration and lower inflammation

• higher cardiorespiratory fitness

metabolically abnormal obese charactersitics

• high fat mass

• low insulin sensitivity

• high ectopic fat

• high triglycerides

• high inflammation

• low HDL-cholesterol

• high intima-media thickness - thick carotid artery wall, atherosclerosis (plaque buildup)

metabolically healthy obese characteristics

• high fat mass

• high insulin sensitvity

• low ectopic fat

• low triglyceriddes

• low inflammation

• high HDL-cholesterol

• low intima-media thickness

modified balke treadmill test to predict VO2 max

• enter information from test (speed, and incline achieved) into reference equations to estimate VO2max

• fitness expressed as metabolic equivalents (METs)

  • 1 MET = 3.5 ml/kg/min

  • ex. 42 ml/kg/min = 12 METs

vo2 max

maximal rate of O2 consumption by the body

• reflects highest rate of oxidative metabolism

determinants of VO2max

• o2 delivery to muscles - CV system

• O2 utlization by muscles - mitochondrial content

aboslute Vo2 max

L/min or ml/min

relative Vo2 max

ml/kg/min - factors in weight

metabolically healthy obese people have higher

CRF than metabolically abnormal obese

metabolically healthy obese have relatively similar hazard ratios for all-cause disease mortality, CV disease mortality, non-fatal CV disease events as (no significant difference)

metabolically healthy normal weight

fitness vs fatness: unfit individuals have

twice the risk of mortality regardless of BMI

overweight and obese-ft indivduals have similar mortality risk as their

normal weight-fit individuals

fitness

best measurement of whole body healthy

having a higher VO2 peak is comparable to having

• lower WC

• lower plasma glucose

• lower BP

survival rates are higher with

higher VO2 max

Wolrd fitness level - test yourself

“feasible and practically useful in primary care for identification of apparently healthy indivduals at increased risk or premature CVD disease and all-cause mortality”

VO2max is very important for

disease risk

for a given fitness level,

the metabolically healthy but obese phenotype is a benign condition (metabolically healthy obese and metabolically healthy normal fat indindivuals have similar prognosis

compensatory behavior in weightloss

automatic or deliberate actions - like eating more food or moving less - that quietly offset the calories you burn during exercise

contribution of physical activity to daily energy expenditure is

fairly low - most of it comes from BMR

predicted weight loss for a 200lb man running 60 min at a moderate-intensity 4x a week

5 lbs at most b/c 3500 calories needed to expend with exercise

dose response of exercise on weight loss in overweight/obese women

• 3 groups of women prescribed exercise at different intensisties (burning 113, 227, 340 kcal per session), longer durations, etc

• weight loss was predicted to increase with intensity, but this was not true

• the middle group had the most amount of weight loss

• key note: as exercise volume increased, you are less likely to lose weight because a major effect of exercise is eating more in response

the more you exercise

the more you eat

exercsie compensation hypothesis

the body and behavior offset the energy deficit from exercise, so weight loss is less than predicted

automatic metabolic exercise compensation hypothesis

• decreases RRE (resting energy expenditure) - because body mass is smaller, body dials down to conserve energy

• increased appetite hormones - more hungry

• decreased energy expenditure of exercise - the same workout costs fewer calories as you get lighter and more efficient

automatic behavioral exercise compensation hypothesis

decreased spontaneous activity - you move less without deciding for example from fatigue

volitional and behavioral exercise compensation hypothesis

• increased energy intake. - eating more, rewarding yourself after a workout

• redduced exercise compliance - skipping or shortening sessions

• decreased non-exercise activity - choosing to sit more, take the elevator, etc.

Exercising in the morning

raises energy expenditure at the time, but participants move less later in the day, so net daily gain is smaller - represents exercise compensation - decreased spontaneous activity

in a study, participants who did not lost the expected weight with an exercise program reported

higher hunger - increased appetitie hormones like ghrelin can drive higher intake and offset the energy deficit from exercise

it is very easy to

out-eat exercise-induced energy expenditure

common compensatory health behavior

good health behaviors can offset bad ones - rewarding exercise with a sweet treat

decreased REE principle

When you lose weight, REE drops. Each kg lost is associated with a decrease in the calories your body burns at rest, so weight loss gets harder over time

obesity cycle explains how

focusing only on weight loss as a primary goal often fails because it keeps people stuck in a loop

the obesity cycle

public desiresweightloss → prescribe weight loss program → obesogenic environment → minimal weightloss → frustration → weight regain → discontinue

diet and exercise

diet can make a major difference in weight loss, the best method is to exercise and have a good diet

contribution of PA to Daily energy expnditure is

quite low

it is difficult to lose weight with exercise alone

there are often large differences between actual and predicted weight loss from exercise

numerous compensatory mechanisms (psyhoclogical and physiological)1

undermine exercise-induced weight loss

old obesity guidelines

• focused solely on achieving weight loss - primary determinant of treatmnet efficacy

• to become “disease-free” one is required to lose weight (achieve BMI under 30)

• successful management targeted a weight loss ofa t least 10% with 3-5% weight loss as the minimal target for clinically meaningful benefit

new obesity guidelines

• focus on improving patient health, not just weight loss

• obesity is a chronic disease that requires long-term management

• obesity management is more tahn reducing numbers on a scale - overall healtha nd well-being over the long term matters

• important part of obesity management is identifying and addressing root causes for weight fain and removing road blocks

• every individual defines success differently

• work towards your “best” weight

GLP-1 (glucagon-like peptide-1)

natural gut hormone to help control blood sugar, slow stomach emptying and reduce appetite

• increases when you eat, act on hypothalamus to modify appetite, tells your brain that you’re full

obesity treatement has entered a new ear

prescription medications! - mimic natural hormone GLP-1

ozempic was

first used for type 2 diabetes because it was so good for monitoring blood sugar

GLP-1 function on pancreas

• increased insulin secretion

• increases new beta-cell formation

• decreases beta-cell apoptosis (death)

• decreased glucagon secretion from pancreatic alpha-cells - help lower blood sugar levels after a meal

GLP-1 function on brain

• increased neurogenesis - new neurons

• increased satiety

• decreased appetite

GLP-1 function on stomach

• increased glucose uptake

• decreased gastric emptying

GLP-1 function on liver

• increased glycogen storage

contemporary obesity management medications produce

substantial weight loss - far greater than what is typically achieved through exercise alone

• semaglutide (Ozempic/wegovy) ~ 15% weight loss in adults without Type 2

• tirzepatide (mounjaro, zepbound) ~ 21% weight loss in adults without type 2

weight loss includes loss of lean tissue

• ~25-40% of weight lost with medication may be lean body mass

  • includes more than just skeletal muscle mass

  • could lead to impaired strength or physiical function

taking medications without exercise

is not good. - it is better to combine both, lifestyle is very important - there is evidence that the health benefits of weightloss are increased with exercise

even in the absence of substantial weight loss, exercise can lower wasit circumference

measures storage of adipose tissues - visceral - abdomincal fat is the most dangerous

during diet-induced restriction

resistance exercise blunts the loss of lean mass

• keeping more lean mass helps hold up REE, counters decreased REE compensation from your earlier slide, makes weight regain less likely

when comparing three groups of different types of exercise in aiding weight loss

• caloric intake was kept stable to reflect changes from exercise

• aerobic and combined exercise had good results. Still, resistance and combined groups gained skeletal muscle mass

• with resistance training, less weight lost is fat-free mass.

• statistically significant difference between groups

preserving lean mass

helps maintain REE, which supports keeping weight off

even in overweight or obese indivduals, endurance training

remodels abdominal subtaneous adipose tissue - higher fitness

even with the same body fat, metabolically healthier fat profile (sedentary vs long-term endurance-trained adults with overweight or obesity) showed -VO2 peak (fitness)

• better vascularization

• less fibrosis and inflammation

• more oxidative capacity

what does exercise show for capillary densitty

more capillaries per adipocyte - improves blood, oxygen, and nutrient flow

higher expression of lipogensis genes in exercise group suggests

greater capacity to store fat in subcutaneous tissue

exercise groups show lower pro-inflammatory macrophages, which suggests

less inflammation

higher expression of oxidative phosphorylation genes indciates

greater mitochondrial oxidative capacity (ATP production) in adipose tissue

biggest limitation of cross-sectioanl exercise study

cannot prove exercise causes differences, but it can show associations

exercise group shows lower levels of Col6a (collagen VI), which suggests

less fibrosis

we need to reframe how we thaink about exercise

• has staggering benefits, will not always help much with just weightloss

• exercise is not a weight loss drug

exercise would be the best prescription if obesity management focused on

• reduced WC

• maintain/increase muscle mass

• decrease functional limitations

• improve cardiorespiratory fitness

• decrease cardiometabolic risk factors

• improve adipose tissue and muscle health

body composition vs body weight alone

Weight doesn’t show how much or how healthy each tissue is

• comp shows volume and quality of each tissue(adipose, lean, bone)