UIowa Obesity Exam 2

What predicts sedentary behavior?

BMI, fat mass, waist circumference

Long Term Regulation Feedback Signals

Leptin and insulin cross blood-brain barrier and circulate and levels proportionate to fat mass

Integration of feeding signals = ________

Long term regulation

Big picture take home message of energy expenditure in youth?

MVPA and TV viewing predict adiposity while total sedentary less important adiposity also predicts future MVPA youth who are active everyday throughout childhood and adolescence are less likely to become obese as adults

MVPA (moderate to vigorous physical activity) its how many METs?

MVPA is >3 METs

Obesity observed in twins

MZ twins strong positive correlation whether reared together or apart

Adult sleep duration 1985 vs 2006

More people getting less sleep observed in every demographic and gender

Dopamine

acts on nucleus accumbens mediates motivating and rewarding aspects of food same response as drugs

What is considered healthy sleep?

adequate duration good quality appropriate timing regularity absence of disturbances or disorders

Weight loss effect on adiponectin

adiponectin increases with weight loss reducing inflammation and insulin resistance

Where are satiety signals produced?

adipose tissue pancreas stomach

What affects our microbiota?

age diet medication weight metabolic state becomes more diverse with weight loss

What supplies neuroendocrine signals that affect energy balance?

alimentary canal

Pramlintide

amylin analog that suppresses for intake in diabetics unique in that administration reduces food intake

Adiponectin

anti inflammatory hormone that is decreased in obese leading to increased inflammation and insulin resistance

What is physical activity and what are the four domains?

any bodily movement produced by skeletal muscles that results in energy expenditure transportation domestic occupation leisure

Define sedentary behavior

any waking behavior characterized by an energy expenditure of <1.5 METs while sitting or reclining

NIH-AARP Diet and Health Study results were _____________ across different categories of age, education, smoking status, baseline BMI, and physical activity level

consistent

Where does Ghrelin act?

hypothalamus and hindbrain sites across bbb via vagus nerve

Physical Activity youth health contributions

improved bone health muscular fitness cardiovascular and metabolic health biomarkers body composition

Higher RQ may be predictive of future ______________ in fat mass

increase

What does overfeeding due to RQ?

increase to as high as 1.3 due to lipogenesis

Total sleep deprivation led to __________ during overnight period of wakefulness

increased caloric intake of 1000kcals during overnight period

What are the hormonal changes associated with sleep loss promoting weight gain?

increased ghrelin increased insulin resistance decreased leptin decreased PYY

Leptin under normal conditions

increased leptin decreased appetite weight maintained

Set Point Theory and body's response to weight gain

increased metabolism decrease in hunger increase in leptin

Fructose lipogenesis

increased visceral adiposity and lipid dysregulation decreased insulin sensitivity

How are new mothers affected by reduced sleep?

increased weight retention

Weight loss does what to ghrelin?

increases ghrelin

Aerobic programs consistent with public health recommendations may promote modest weight loss ~2kg but weight loss on an _____________ is highly ________________

individual level heterogeneous

Risperidone vs energy expenditure

induced shifts in gut microbiome that cause decrease in non-aerobic RMR opposite of what DNP does

Brain response to lack of signals being sent

initiate feeding

Hypothalamus = signal _______ Afferent center of hind brain = signal _______

integrated processed

Where are long term regulation signals integrated and processed?

integrated at the hypothalamus processed at afferent center of hindbrain

Energy balance is an _____________ endpoint

integrated endpoint

What does GLP-1 regulate?

integrated in many pathways and signals satiety

Long term CCK interactions

interacts with leptin and insulin spanning both short and long term signal pathways

CCK interaction

interacts with stomach distention for short term feeding reduces gastric emptying

Brain response to signals being sent during feeding

intiate satiety

What is the relationship between hours per week of vigorous physical activity and incidence rate of obesity

inverse relationsip more active = less likely obese

Leptin

key adipose signal secreted into blood from fat cells acts at hypothalamus to suppress food intake

Insulin

key pancreatic signal made by islet cells supposed to act centrally at hypothalamus to reduce food intake and weight lipostatic signal

Why is TV viewing a good proxy of sedentary behavior?

know how long shows are and can count shows easily

leptin under chronic obesity

leptin deficiency appetite not affected weight gain

What percent of U.S. adults exercise regularly?

less than 5%

Recommended sleep hygeine

limit daytime naps to 30 min exercise minimum 10 minutes daily create optimal sleep environment establish relaxing routine

What is the problem with added sugars?

liquid sugars less satiating, more addicting, lead to more weight gain

Obesity rates among US immigrants

living in US for 15 years associated with BMI increase for all immigrant subgroups except foreign born blacks suggests environment responsible for short term changes

Reward system and addiction

located in nucleus accumbens chronic stimulation with sugar down regulates dopamine receptor and blunts reward response results in tolerance and withdrawal if removed

Set Point Theory and body's response to weight loss

lower metabolism increase in hunger decrease leptin

What is a higher Diet Quality Score (DQS) associated with?

lower risk of short sleep less than seven hours in men and women

Amylin

made in pancreas and is co-secreted with insulin satiation signal that acts at receptors in hind brain regulates glycemic control through gastric emptying might enhance effects of leptin

what regulates digestive efficiency?

material consumed body gut microbiota

Fecal acid steatocrit (qualitative)

measure amount of fat lost to feces

Bomb calorimetry (quantitative)

measures caloric density of food vs feces

Direct calorimetry

measures energy expenditure by assessing heat generated by an organism gold standard but expensive and difficult

Indirect calorimetry

measures oxygen consumed and CO2 produced to estimate basal energy expenditure and resting energy expenditure fairly accurate and practical

Fructose

metabolized in liver to fat more lipogenic than glucose

Effect of disease on gut microbiome

microbiome becomes less diverse

How does the body defend its mass?

modifies RMR to resist weight loss

Weight loss from surgery

more robust gut bacteria can lead to health benefits

Is obesity heritable?

more than 50 genes linked to obesity 60-70% of heritability in BMI attributable to genetic variations while remaining 30-40% due to environment/behavior

Larks peak in the _______ while Owls peak in the _________

morning evening

genetic mutations causing obesity

most are polygenic variations although a continuum exists between the two forms 4 genes involved

White adipose tissue (WAT)

most common fat type mostly used for storage

What may contribute to resistance in weight gain?

naturally occurring and dietary choice induced differences in digestive efficiency

Exercise contribution to TEE

negligible for most

CCK Drugs

no safe drugs body quick to adapt

Physical activity and weight loss

not effective alone for weight loss assists in weight loss and weight management

GIP drug therapy

not good for drug therapy as signaling action not working in diabetics and might impair glucose tolerance

Brown fat activation during cold exposure in lean vs obese

not present or not active in obese individuals

Ghrelin paradox

obese have lower circulating levels vs lean adults and post-feeding suppress not as large in obese

Leptin paradox

obesity causes chronic increase in leptin and brain develops resistance and fails to respond

Both parents OW/OB

offspring 6x more likely to be OW/OB at 21

Leptin oversaturation

over saturation at brain receptors decreases receptor response such that leptin fails to suppress food intake and increase energy expenditure vicious cycle

Higher digestive efficiency

packing on more calories weight gain

Orlistat

pancreatic lipase inhibitor that prevents processing of fats and reduces digestive efficiency behavioral modifier - patients don't like sharting

Why is Orlistat ineffective long term?

patients change their food choices

Observational study of sedentary time and adiposity among youth results

physical activity more important predictor of weight status in youth than sedentary behavior or TV viewing

what is the best predictor of lower obesity in youth?

physical activity most important for reducing odds of developing obesity

polygenic predisposition to obesity

points to a key role of CNS in body weight regulation influencing appetite, metabolism ,digestive efficiency, etc.

Epigenetics and obesity

poor nutrition habits during development can change expression of genes and increase predisposition to obesity slight changes occurring because of the changed toxic environment

What is the relationship between HFCS and diabetes?

positive correlation

What is the relationship between MET-hours per week and the odds ratio of maintaining a healthy weight?

positive relationshio more METS - more likely healthy weight

What is the relationship between short sleep duration (<7hr) and obesity?

positive relationship between short sleep and obesity incidence of both have increased over time

How do we identify metabolically active tissues?

positron emission tomography (PET) metabolically active tissue absorbs more glucose than inactive tissue

How does inhibition of feeding arise

primarily for mechanical GI signals

Serotonin

primary inhibitory signal secreted from gastric cells

Energy homeostasis in response to weight gain

process of increased size and number of fat cells is unopposed by body systems no biological response

Peptide YY (PYY)

produced in large and small intestines after feeding co-released with GLP-1 optimistic about future

define neuropeptides

protein-like molecules that act as neurotransmitters

Heritability of obesity

significant familial heritability observed for BMI, % body fat, metabolism, physical activity and eating behaviors statistically significant constant positive correlation

What are the adverse health outcomes associated with Owl chronotype?

sleep problems eating disorders mental conditions metabolic dysfunction obesity

Overall measure of____________ may be a ___________ predictor of obesity than individual ___________.

sleep quality stronger sleep disturbances

Social jet-lag and BMI

social jet-lag is a predictor of BMI especially for the overweight

Ghrelin

sole gut peptide classified as hunger hormone produced in stomach want to suppress to decrease hunger feeling

Children are eating _________ recommended amount of _____________

three times added sugar

What are the hallmarks of addiction?

tolerance and withdrawal

Lipostatic model with low signals

too little fat intake increased and expenditure is reduced to drive positive energy balance resulting in increase fatness

Lipostaic model with high signals

too much fat expenditure increased and intake decreased until fatness falls

Obesity vs HCFS trends

trend the same way positive correlation

True or false WAT is metabolically inactive

true

Ghrelin drug therapy

undesirable side effects

Is sleep quality subjective of objective?

very subjective and does not correlate with objective measurements

Energy homeostasis responds more vigorously to __________ than _________

weight loss weight gain

Cholecystokinin (CCK)

within meal satiation neuropeptide released from intestinal cells and stomach primary acts at afferent terminals of vagus nerve

Non-exercise activity thermogenesis (NEAT)

working, fidgeting, and other ADL not including physical exercise often widest variance in energy expenditure

Dietary guidelines recommend _______ kcal from sugar

<10%

Adolescent sugar consumption recommendation vs current consumption

<25g/day 80g/day

Sleep restriction associated with _________________ in energy expenditure?

+100kcal/day increase

"Active" metabolic rate can account for ________ of total metabolic rate

0-40%

What is the odds ratio for short sleep and obesity in adults?

1.55 55% increased risk

Light METs

1.6-2.9 walking slowly or cooking a meal

What is the odds ratio for short sleep and obesity in children?

1.89 89% increased risk

Pre-School sleep duration

10-13 hours

Toddler sleep duration

11-14 hours

Infant sleep duration

12-15 hours

Newborn sleep duration

14-17 hours

ACSM volume of PA to maintain weight and improve health

150 min/wk

ACSM volume of PA for prevention of weight gain

150-250 min/wk

When is the circadian rhythm most sensitive to light?

2 hours before bed until 1 hour before wake

ACSM volume of PA for prevention of weight gain AFTER weight loss

200-300 min/wk

ACSM volume of PA to promote clinically significant weight loss (3-5% BW)

225-420 min/wk

Moderate METs

3.0-5.9 mowing lawn vacuuming can maintain conversation

Orlistat effectiveness one-year clinical trial

35-55% had 5% greater weight loss and 16-35% had 10% greater weight loss compared to diet and exercise alone

Vigorous METs

>6.0 cannot maintain conversation walking fast running

NIH-AARP Diet and Health Study participants who reported <5 hours of sleep per night had ______________ of developing obesity than those who reported 7-8 hours of sleep

40% higher risk

Prospective study of sedentary behavior and obesity predictions

5.6 year study sedentary time did not predict future obesity

Orlistat effectiveness four-year clinical trial

5.8kg weight loss stopping drug resulted in 35% weight regain in most slight reduction in T2D risk in obese patients and may reduce BP slightly in long term

what amount of physical activity is best predictor of lower obesity?

55 minutes a day of moderate to vigorous physical activity

TEE of moderately sedentary individuals:

55-75% RMR 15-30% physical activity 7-15% dietary thermogenesis

RMR can account for _______ of total metabolic rate

60-75%

Older adult sleep duration (65+)

7-8 hours

Young adult - Adult sleep duration

7-9 hours

What is the current estimated energy imbalance gap in the US?

7.2 cal/day

Teen sleep duration

8-10 hours

School age sleep duration (big drop)

9-11 hours

Sedentary METs

<1.5 sitting or reclining activities

Respiratory quotient

CO2 production/O2 consumption

when does chronotype reach its maximum in lateness?

Early adulthood

True of False: Sleep restriction only impacts appetite regulating hormones and does not affect other neural activity

False Sleep restriction impacts neural activity and appetite regulating hormones

True or False The long term trends for Energy Expenditure do not match obesity?

False long term trends for energy expenditure match obesity

Adolescent sleep duration 1991 vs 2012

Fewer kids reporting lower amounts of sleep

Liraglutide

GLP-1 receptor agonist that suppress appetite by increasing insulin release from pancreas and decrease glucagon release frequent injections and expensive

HFCS and Leptin

HFCS causes big spike in insulin that decreases leptin efficacy in hypothalamus

Maternal high fat diet (HFD)

HFD-fed offspring had increased anxiety and decreased voluntary physical activity lower energy expenditure weighed more at adulthood than control fed

What is the gold standard method of non-calorimetric energy expenditure measurements?

Harris-benedict equation but difficult to do

What can explain perceptions that some individuals are "naturally skinny?

NEAT

Are there associates for occupational PA or SB and health?

No

Parental Pre-pregnancy weight

OW/OB increases risk high birth weight pre-pregnancy BMI predicts offspring BMI at 21 years

Which macronutrient has the highest TEF?

Protein has TEF 5x greater than CHO and lipids

What makes up total energy expenditure?

RMR NEAT thermic effect of meals exercise if present

Energy Expenditure: Direct Calorimetry Formula

Total energy expenditure = 60% from heat + 40% from ATP production

True or False: Restricted sleep negatively impacts diet quality and increases caloric consumption

True

What is the relationship between BMI, fat mass, waist circumference and sedentary behavior?

Unidirectional relationship sedentary behavior did not predict BMI fat mass or waist circumference

Risperidone

atypical antipsychotic causes weight gain and T2D negative effect on gut

Long Term Regulation

based on energy stores (hormones and neurons) hypothalamus

High leisure PA group study results

better BMI and mood

what is the highest food on the satiety index?

boiled potatoes

Diet Induced Thermogenesis

caloric cost of digesting and processing nutrients 10% of TEE

Is exercise or caloric restriction more important for weight loss?

caloric restriction

What modality produces the most initial weight loss with what is the possibility?

caloric restriction and aerobic exercise very possible

Gut RMR suppression

can contribute to obesity ~29lbs per year from risperidone

Visceral fat

centrally located around organs strongly associated with CVD, HTN, diabetes and metabolic syndrome

mono genetic mutation cases

childhood formed rare and severe

What happens to circadian rhythm with age?

circadian rhythm becomes less robust with age due to less light exposure and less hormone secretion

AT neural control circuitry

complex neural circuitry controls activation of cardiovascular, shivering and non-shivering thermogenic responses to ambient skin temperatures

Energy homeostasis in response to weight loss

decrease REE decrease TEE decrease caloric needs but increase excess caloric storage

What does underfeeding do to RQ?

decrease in RQ due to lipolysis

Leptin with weight loss

decrease leptin increased appetite decrease energy expenditure decrease reproductive capacity

Sleep duration ______ over lifespan

decreases

energy imbalance gap

difference in energy intake vs output results in excess energy storage (obesity)

What biological mechanisms contribute to energy imbalance and obesity?

digestive efficiency RMR fat type

Leptin Dose Response

dose response relationship with weight and fat loss observed with leptin injections weight loss variable and most individuals had little to no effect from leptin (resistant)

GEMINAKAR twin study conclusions

for the majority of dietary variables genetic influence was 20-50% both diet and anthropometry are influenced by genetic variation high PA associated with down-regulation of genes predisposing to obesity

Sleep quality vs sleep duration

effects of sleep quality on obesity are independent of sleep duration sleep quality has stronger effect on obesity than sleep duration in young adults

Thrifty genes

enable individuals to efficiently collect and process food to deposit fat good during famine bad during food abundance imbalance between current environment and biology make it harder to lose weight

Obesity the result of a failure of what?

energy balance biological mechanisms contribute to both energy intake and energy output

Resting Metabolic Rate (RMR)

energy expended at rest, does not require overnight supine measurement increased with increased body weight easier to measure

Basal Metabolic Rate (BMR)

energy expended while fasting, rested, and supine in thermoneutral environment increased with increased body weight hard to measure

What does brown adipose tissue facilitate?

energy expenditure and increases metabolic rate

Harris-Benedict Equation

estimates energy expenditure accounting for age, gender, height and weight

Exercise vs caloric restriction in weight loss

exercise plus caloric restriction achieves same weight loss as caloric restriction alone

If diet is most important for weight loss, what is exercise good for?

exercise provides modest benefit for weight maintenance

variability of fat gain (during overfeeding in lean humans)

fat gain varied 10 fold supports concept of obesity prone and obesity resistant humans

FTO gene

fat mass and obesity associated gene

Short Term Regulation

feeding stimulated by environment and bio signals from regulatory system provides substrates to body signals of taste and stomach distention are processed at afferent center of hindbrain

Interaction of environment and genetic variance

genetics play a role but driven by environemnt recent changes due to HFCS expose genetically sensitive individuals leading to obesity

What activities contribute to "active" metabolic rate?

going to class, making lunch, exercise

Brown adipose tissue

heat producing tissued located in neck, upper thorax and surrounding organs more plentiful among lean

Types of food that induce fullness and weight management

high protein - gherkin GLP-1 high fiber - bulk, slow stomach emptying high volume - water/air low energy density - low cals/volume

High leisure SB group study results

higher BMI and body fat % higher waist circumference worse mood

Sugar video THM

highly processed foods in American diet cause huge spike in insulin and because of the addictive properties we keep eating these foods over-insulinizing the population. Prevents leptin from acting a the brain but insulin hijacks process and body becomes leptin resistant with no strong signal to tell body to stop eating

New food environment

hijacking body's response to leptin and insulin increased insulin levels shunt sugar to fat and blocks leptin at the brain resulting in energy storage and still hungry

What regulates timing, intensity, and duration of sleep?

homeostatic regulation and circadian timing

define gut peptides

hormones that regulate feeding behavior before and after meals signals originate in the gut and are sent to brain

Adaptive thermogenesis (AT)

how body makes heat in response to cold environment raises RMR

Roux-en-Y gastric bypass benefits

huge effect on weight loss benefits may come from structural changes that increase gut bacteria biomass

how do the gut peptides communicate with the brain?

humoral communication via vagus nerve and splanchnic pathway

Where are short term regulation signals integrated and processed?

signals sent to afferent center of hindbrain then hypothalamus

adipokines

proteins produced by both fat and nonfat cells become necrotic in obese and pro-inflammatory

Gut responds to ______ over _______

quantity over quality

Sleep health disparities

racial minorities and lower SES more likely to experience poor sleep patterns associated with adverse health outcomes

Metabolic Equivalents (METs)

ratio of rate of energy expended while performing activities compared to reference

FTO deficiency

reduce fat mass in mice though increased energy expenditure

What can PA reduce in children and adolescents?

reduced symptoms of depression

Lower digestive efficiency

reduces calories absorbed relative to calories consumed

Dieting = Inhibiting Reward

requires active inhibitory control of feeding goes against evolutionary adaptation of hedonic feeding to store fat to survive possible rationale for poor long term diet adherence

What can be an indirect estimate of the kinds of foods one is consuming?

respiratory quotient

Glucagon-like peptide 1 (GLP-1)

secreted by enteroendocrine cells in small and large intestine in response to food acts at vagus nerve via GLP-1 receptor

NIH-AARP Diet & Health Sleep Study Results

short sleep associated with higher risk of obesity in middle to old aged men and women short sleep <5 hours associated with more weight gain

What were the conclusions from the Physical Activity and the Prevention of Weight Gain in Adults: A Systematic Review?

strong evidence of association between physical activity and prevention of weight gain in adults with based on limited evidence in adults - dose response relationship and prevention of weight gain most pronounced when MVPA is above 150 min/wk Insufficient evidence to determine associate between light intensity (<3 METs) activity and reduced weight gain in adults

Environment vs genetics

strong genetic biological influence on body weight in children

Most common added sugar

sucrose and HFCS

Central clock

suprachiasmatic nucleus în hypothalamus controls circadian rhythm

Gastric Inhibitory Polypeptide (GIP)

synthesized in duodenum and jejunum of GI stimulates glucose-dependent insulin secretion in pancreas

What factor has changed over last 50 years?

the changing toxic environment and resulting behavior is responsible for rising prevalence rates

What is person's chronotype?

the propensity for the individual to sleep at a particular time during a 24 hour period