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
