Environmental Links to Children’s Obesity

Helen J. Binns, MD, MPH Ann & Robert H. Lurie Children’s Hospital of ChicagoFeinberg School of Medicine, Northwestern UniversitySponsored by Region 5, Pediatric Environmental Health Specialty Unit

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Disclosure Information

• This material was supported by the Association of Occupational and Environmental Clinics (AOEC) and funded under the cooperative agreement award number 1U61TS000118-03 from the Agency for Toxic Substances and Disease Registry (ATSDR).

• Acknowledgement: The U.S. Environmental Protection Agency (EPA) supports the PEHSU by providing funds to ATSDR under Inter-Agency Agreement number DW-75-92301301-0. Neither EPA nor ATSDR endorse the purchase of any commercial products or services mentioned in PEHSU publications.

• Dr. Binns has no conflicts of interest to disclose.

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Overview Prevalence Key time periods Regulation of eating Environmental pollutants

1998

Obesity Trends* Among U.S. AdultsBRFSS, 1990, 1998, 2008

(*BMI 30, or about 30 lbs. overweight for 5’4” person)

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

  Survey Periods

NHANES II1976–1980

NHANES III1988–1994

NHANES1999–2002

NHANES2003–2006

NHANES2009–2010

Ages 2 -5

5% 7.2% 10.3% 12.4% 12.1%

Ages 6 - 11

6.5% 11.3% 15.8% 17.0% 18.0%

Ages 12 - 19

5% 10.5% 16.1% 17.6% 18.4%

*Sex-and age-specific BMI ≥ 95th percentile based on the CDC growth chartsSources:Ogden CL, et al JAMA 2002;288:1728–32.Hedley AA, et al JAMA 2008;299:2401–5.Ogden CL, et al JAMA 2012;307:483–90.

Prevalence of Obesity* Among U.S. Children and Adolescents (Aged 2–19 Yrs)

Even Babies are Too Big!

6Ogden CL, et al JAMA 2012;307:483–90.

Key time periods

Prenatal environment Maternal pre-pregnancy weight Maternal glucose control Maternal weight gain during pregnancy Maternal nutrition Maternal environmental exposures

(including tobacco smoke)

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Pre-Pregnancy & Pregnancy: Normal birth weight babies of obese mothers

Increased obesity in childhood Increased insulin resistance as young adults

Maternal smoking during pregnancy increases likelihood of obesity at ages 5-6 years

17% OW vs. 8% for non smokers Lower BW and catch up growth Deficit in appetite control

Genetics and Biologic Risks: The Prenatal Environment

Cellular memory of insulin response in target tissues (eg, adipose tissue, skeletal muscle) is established in utero Glucose exposure in utero

Influences fetal development of insulin sensitivity risk of type 2 diabetes regardless of DM type or

infant BW Response to fetal malnutrition

“thrifty phenotype” hypothesis Small for gestational age babies

obesity; cell function

Dabelea D, et al. Diabetes 2000;49:2208-11Gillman MW, et al. Pediatrics 2003;111:e221-6Lunde A, et al. Am J Epidemiol 2007;165:734-41

10Copyright ©2003 The Endocrine Society

Catalano, P. M. J Clin Endocrinol Metab 2003;88:3505-3506

Genetics and Biologic Risks: Importance of the Prenatal Environment

Exposure cause Epigenome changes Influences protein expression and can be long-lasting

(eg. fetal programming) -- inherited across generations.

Changes how tightly DNA is coiled Alterations of gene expression

Influenced by environmental exposures (eg, BPA in animal models, PCBs, hexachlorobenzene) & nutrition

Dabelea D, et al. Diabetes 2000;49:2208-11Gillman MW, et al. Pediatrics 2003;111:e221-6Lunde A, et al. Am J Epidemiol 2007;165:734-41

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Changing Biologic Risk

http://nihroadmap.nih.gov/epigenomics/epigeneticmechanisms.asp

Toxic Exposures In Pregnancy Raise Rates Of Child Obesity

Endocrine disrupting chemicals (animal, human studies)

Glucocorticoids, other hormones, some plastics, some pesticides (many banned in US)-ongoing study

Proposed mechanisms Disruption of processes controlling eating, activity,

metabolism, and fat formation During critical developmental windows, e.g., formation of

appetite and satiety centers in brain

Salsberry & Reagan 2005, Oken E et al 2008, Olson et al 2009, Smink A et al 2008, Heindel and vom Saal 2009, Espositio L et al 2009

Weight gain in the early months and years

Multiple studies show that no matter what the heaviness at birth, faster gain means a heavier child (controlling for other factors)

• 1st 6 months• 1st year• 1st 2 years

15Taveras EM, et al. Pediatrics 2009;123:1177-83

Heaviest at 6 months Heaviest

at birth

Rapid Weight Gain Obesity at 3 Years

Project Viva 559 children, 72% white, 74% college-educated mothers

Weight at 6 months predicts obesity at 3 years

Predicted probabilities of BMI 85th percentile at age 12, as a function of BMI by age

Nader PR et al. Pediatrics 2006;118:e594

BMI 75th% at 2-4y then, >50% OW/obese at 12 yrs.

Genetics and Biologic Risks

Whitaker et al, N Engl J Med 1997;869-73

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Child Age & Weight Status

Influence of Child and Parental Weight Status on Obesity as a Young Adult

Child Age: 1-2y 3-5y 6-9y 10-14y 15-17y

Parent

Obese

Not obese

Genetics and Biologic Risks

Biologic response to excess calories

Twin Study Monozygotic twins Overeating 1000 Kcal/day for

~ 3 months

Twins pairs more similar to each other that non-related individuals

Twin status explained 55% of gain pattern

Bouchard et al, N Engl J Med. 1990;322:1477-82.

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Overview Prevalence Key time periods Regulation of eating Environmental pollutants

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Regulation of Eating

Sensory factors: TasteSmell

Texture Sight

Effects of:Variety

Sensory-specific satietyPalatability

Food concentrationReady availability

Brain mechanisms:Modulate sensory factors by

satiety signals to produce reward value and appetite

Eating

from Rolls ET. Obes Rev 2007;8(suppl 1):67-72

Satiety/hunger signals:Adipose tissue signals

Gut hormonesGastric distension

Cognitive factors: Conscious rational control

Beliefs about the foodAdvertising

Family & Social Influences

Weight Status Food Content

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Brain Signaling of Eating

http://www.cellbiol.net/ste/alpobesity4.php

• I’m full• PYY (peptide YY)• Insulin• Leptin• CCK (cholecystokinin)

• I’m hungry• Ghrelin

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Brain Signaling of Eating

http://www.cellbiol.net/ste/alpobesity4.php

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Adipose Tissue is VERY Metabolically ActiveAdipose Tissue is VERY Metabolically Active

Reprinted in adapted form from Trayhurn P, Wood IS. Br J Nutr. 2004;92:347–355, with permission of Cambridge University Press. | Eckel RH, et al. Lancet. 2005;365:1415–1428. | Lyon CJ, et al. Endocrinology. 2003;144:2195–2200.

CRP = C-reactive protein; IL-6 = interleukin-6; TNFα = tumor necrosis factor-alpha

InflammationInflammation Atherogenic DyslipidemiaAtherogenic Dyslipidemia

Type 2 DiabetesType 2

Diabetes

ThrombosisThrombosis

AtherosclerosisAtherosclerosis

HypertensionHypertension Lipoprotein lipaseLipoprotein lipase

AngiotensinogenAngiotensinogen IL-6IL-6

CRPCRP

Plasminogen Plasminogen activator inhibitor-1activator inhibitor-1 (PA-1) (PA-1)

InsulinInsulin

LactateLactate

ResistinResistin

LeptinLeptin

AdiponectinAdiponectin

TNF TNF

AdipsinAdipsin(Complement D)(Complement D)

Free Fatty Free Fatty AcidsAcids

Slide SourceLipids Online Slide Librarywww.lipidsonline.org

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Actions on Fat Cells

PPAR – peroxisome proliferator-activated receptors bind a wide range of compounds Fat cell proliferation and differentiation Function of macrophages in adipose tissue

Endocrine disruptors change sex steroid actions Influence fat tissue development Influence remodeling of fat

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U-shaped Dose Response

Developmental exposure to PFOA (perfluorooctanoic acid)

Impart water and grease resistance – eg, non-stick pans, food wrappers

Weight – day 1 Weight – week 20-29

Hines EP. MolCellEndocrinol 2009

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Overview Prevalence Key time periods Regulation of eating Environmental pollutants

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Obesity = Energy Balance Problem

http://www.precisionnutrition.com/expert-tip-make-it-simple

Toxic Environment 1 – Screens

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2002-6 = 1.5 TVs 2007-10 = 3 TVs 40% TV w/ meals Fewer fruits & veggies

pizza, snack foods, sodas High exposure to advertisement of

unhealthy food

Toxic Environment 2 – TV ads

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Toxic Environment 3 – fast food

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Toxic Environment 4 – supersize

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Toxic Environment 5 – no-low veggies

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Toxic Environment 6 – sugary drinks

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Child Factors Associated with Higher Weight

Rapid rate of eating High heritability of eating rate = 0.62

High food-cue responsiveness More focused on food More impulsive when making food choices More motivated for immediate rewards, such as

good taste Low satiety responsiveness

Carnell S, Wardle J. Am J Clin Nutr. 2008;88:22-9; Epstein LH et al. Learn Motiv. 2008;39:243-44Temple JL, et al. Am J Clin Nutr 2008;87:1121-7;Llewellyn CH, et al. Am J Clin Nutr 2008;88:1560-1566 Epstein LH, et al. Eat Behav 2008;9:319-27

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Influence of Peers

Peers can promote healthier food choices The best predictor of selection of healthy snack foods

is other peers consuming healthy snack foods True for both overweight and lean children

When overweight children are alone Eat more (than if with their peers) Eat more (than lean children who are alone)

Peer influences become stronger as children age

Romero ND, et al. J Am Dietetic Assoc 2009:109:133-6Salvy SJ, et al. Eat Behav 2008;9:190-6

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Environmental Exposures & Biologic Risk

Miyawaki J. JAtherosclerThromb 2007Ben-Jonathan N. MolCellEndo 2009Rubin BS. MolCellEndo 2009

Agent Effects

Bisphenol A body weight (%fat) & hyperlipidemia (animal) “U” shaped activity curves Promotes insulin release Prolonged exposure hyperinsulinemia & insulin resistance

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Environmental Exposures & Biologic Risk

Miyawaki J. JAtherosclerThromb 2007Ben-Jonathan N. MolCellEndo 2009Rubin BS. EnviornHealthPerspect 2001

Agent Effects

Bisphenol A Effects on adipose tissue: adiponectin release ( regulator of insulin sensitivity and tissue inflammation) IL-6 and TNF- release ( promotes inflammation) up-regulates genes for adipocyte differentiation (PPAR) – thus, increase adipocyte number

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Environmental Exposures May Change Biologic Risk

Agent Effects

Phthalates softener for plastics,

lotions, shampoos Most exposures through

food & medical

Disturbed lipid and steroid metabolism androgen antagonist

Possible pro-adipogenic actions Activate PPAR receptors – changes to adipocyte differentiation ( #) Disturbs transcriptional regulation of testicular steriodogenesis ( androgen biosynthesis)

Girls grow more rapidly, puberty earlier; boys puberty later

Grun F. MolEndocrinol 2009

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Environmental Exposures May Change Biologic Risk

Agent Effects

PBDE (polybrominated

diphenyl ethers) Flame retardants

Higher levels associated with obesity and metabolic syndromeDisturbs thyroid hormone axis

Exposure during gestation affects thyroid morphology

Grun F. MolEndocrinol 2009Lim JS. DiabCare 2008

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Environmental Exposures May Change Biologic Risk

Agent Effects

Organotins PVC plastics, fungicides, pesticides

# and ectopic adipocyte formation Works through PPAR or PPAR-like junctions masculinization process in certain species

Grun F. MolEndocrinol 2009;23:1127-34Grun F. RevEndocrMetabDisord 2007Blount B. EnvironHealthPerspect 2000

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Summary

Early risks set the stage – prenatal and infancy

The physical environment and habits can be toxic

Established obesity changes physiologic responses to promote obesity.

Other environmental exposure may play a role.