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Cited by 30Toxic Organic Pollutants ImpactBirth, Development, and HealthAdipose Tissue and Metabolism

Exposure to environmentally persistent free radicals during gestation lowers energy expenditure and impairs skeletal muscle mitochondrial function in adult mice

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Stephenson, Erin J., Ragauskas, Alyse, Jaligama, Sridhar, Redd, JeAnna R., Parvathareddy, Jyothi, Peloquin, Matthew J., Saravia, Jordy, Han, Joan C. +2 more·2016·American Journal of Physiology-Endocrinology and Metabolism
DOI 10.1152/ajpendo.00521.2015PMC PMC4935140
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Abstract

We have investigated the effects of in utero exposure to environmentally persistent free radicals (EPFRs) on growth, metabolism, energy utilization, and skeletal muscle mitochondria in a mouse model of diet-induced obesity. Pregnant mice were treated with laboratory-generated, combustion-derived particular matter (MCP230). The adult offspring were placed on a high-fat diet for 12 wk, after which we observed a 9.8% increase in their body weight. The increase in body size observed in the MCP230-exposed mice was not associated with increases in food intake but was associated with a reduction in physical activity and lower energy expenditure. The reduced energy expenditure in mice indirectly exposed to MCP230 was associated with reductions in skeletal muscle mitochondrial DNA copy number, lower mRNA levels of electron transport genes, and reduced citrate synthase activity. Upregulation of key genes involved in ameliorating oxidative stress was also observed in the muscle of MCP230-exposed mice. These findings suggest that gestational exposure to MCP230 leads to a reduction in energy expenditure at least in part through alterations to mitochondrial metabolism in the skeletal muscle.

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  • Male mice exposed in utero to combustion-derived PM0.1 had increased weight gain compared with controls after placement on a high-fat diet for 12 weeks, not associated with increased food intake but correlated with lessened physical activity and energy expenditure.

    “Stephenson et al. [75] reported that male mice exposed in utero to combustion-derived PM0.1 had increased weight gain in comparison to controls after placement on a high-fat diet for 12 weeks (from 10-22 weeks of age). Increased body weight was not associated with increased food intake, but correlated with lessened physical activity and energy expenditure.”

    From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [75]

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  • Maternal fine and ultrafine PM exposure has been linked with offspring metabolic disorders via mitochondrial oxidative stress.

    “Since maternal fine and ultrafine PM exposure has been linked with offspring metabolic disorders via mitochondrial oxidative stress [75], targeting these pathways may also potentially prevent metabolic dysfunction.”

    From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [75]

    The Results and Discussion report that gestational exposure to EPFR-containing particulate matter in mice was associated with larger offspring, reduced energy expenditure, and impaired skeletal-muscle mitochondrial function. The Discussion says oxidative stress is a possible mechanism, not an established pathway. Our copy does not identify the tested particles as both fine and ultrafine PM. (LLM, conf=0.86)

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  • The increased weight gain after in utero PM0.1 exposure corresponded with reductions in skeletal muscle mitochondrial DNA copy number, lower expression of electron transport genes, and reduced citrate synthase activity.

    “This corresponded with reductions in skeletal muscle mitochondrial DNA copy number, lower expression of electron transport genes, and reduced citrate synthase activity.”

    From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [75]

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Research works printed but not linked: 46

  1. [1]Allister EM, Robson-Doucette CA, Prentice KJ, Hardy AB, Sultan S, Gaisano HY, Kong D, Gilon P, Herrera PL, Lowell BB, Wheeler MB UCP2 regulates the glucagon response to fasting and starvation. Diabetes 62: 1623– 1633, 2013. 23434936 PMC3636632
  2. [2]Andersen ZJ, Raaschou-Nielsen O, Ketzel M, Jensen SS, Hvidberg M, Loft S, Tjønneland A, Overvad K, Sørensen M Diabetes incidence and long-term exposure to air pollution: a cohort study. Diabetes Care 35: 92– 98, 2012. 22074722 PMC3241311
  3. [3]Baggio LL, Huang Q, Brown TJ, Drucker DJ Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 127: 546– 558, 2004. 15300587
  4. [4]Bates D, Mächler M, Bolker B, Walker S Fitting Linear Mixed-Effects Models using lme4. ArXiv 1406.5823: 1–51, 2014. · arXiv
  5. [6]Bolton JL, Smith SH, Huff NC, Gilmour MI, Foster WM, Auten RL, Bilbo SD Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner. FASEB J 26: 4743– 4754, 2012. 22815382
  6. [7]Brook RD, Jerrett M, Brook JR, Bard RL, Finkelstein MM The relationship between diabetes mellitus and traffic-related air pollution. J Occup Environ Med 50: 32– 38, 2008. 18188079
  7. [8]Brown LD Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health. J Endocrinol 221: R13– R29, 2014. 24532817 PMC4004098
  8. [9]Burke V, Gracey MP, Milligan RA, Thompson C, Taggart AC, Beilin LJ Parental smoking and risk factors for cardiovascular disease in 10- to 12-year-old children. J Pediatr 133: 206– 213, 1998. 9709707
  9. [10]Cakmak S, Dales R, Leech J, Liu L The influence of air pollution on cardiovascular and pulmonary function and exercise capacity: Canadian Health Measures Survey (CHMS). Environ Res 111: 1309– 1312, 2011. 22000598
  10. [11]Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, Horvath TL The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37: 649– 661, 2003. 12597862
  11. [12]Crawley HF, While D Parental smoking and the nutrient intake and food choice of British teenagers aged 16–17 years. J Epidemiol Community Health 50: 306– 312, 1996. 8935463 PMC1060288
  12. [13]dela Cruz AL, Gehling W, Lomnicki S, Cook R, Dellinger B Detection of environmentally persistent free radicals at a superfund wood treating site. Environ Sci Technol 45: 6356– 6365, 2011. 21732664 PMC3167238
  13. [14]Cutrufello PT, Rundell KW, Smoliga JM, Stylianides GA Inhaled whole exhaust and its effect on exercise performance and vascular function. Inhal Toxicol 23: 658– 667, 2011. 21867399
  14. [15]Dellinger B, Pryor WA, Cueto R, Squadrito GL, Hegde V, Deutsch WA Role of free radicals in the toxicity of airborne fine particulate matter. Chem Res Toxicol 14: 1371– 1377, 2001. 11599928
  15. [16]Dunlop K, Cedrone M, Staples JF, Regnault TR Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity. Nutrients 7: 1202– 1216, 2015. 25685986 PMC4344584
  16. [17]Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD Superoxide activates mitochondrial uncoupling proteins. Nature 415: 96– 99, 2002. 11780125
  17. [19]Fox J, Weisberg S An {R} Companion to Applied Regression, Second Edition. Thousand Oaks, CA: Sage, 2011.
  18. [20]Gali Ramamoorthy T, Laverny G, Schlagowski AI, Zoll J, Messaddeq N, Bornert JM, Panza S, Ferry A, Geny B, Metzger D The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defence in skeletal muscles. Nat Commun 6: 10210, 2015. 26674215 PMC4703903
  19. [22]Janssen BG, Munters E, Pieters N, Smeets K, Cox B, Cuypers A, Fierens F, Penders J, Vangronsveld J, Gyselaers W, Nawrot TS Placental mitochondrial DNA content and particulate air pollution during in utero life. Environ Health Perspect 120: 1346– 1352, 2012. 22626541 PMC3440109
  20. [23]Ježek P, Hlavatá L Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int J Biochem Cell Biol 37: 2478– 2503, 2005. 16103002
  21. [24]Johnson RK, Wang MQ, Smith MJ, Connolly G The association between parental smoking and the diet quality of low-income children. Pediatrics 97: 312– 317, 1996. 8604263
  22. [28]Li R, Kou X, Geng H, Xie J, Tian J, Cai Z, Dong C Mitochondrial damage: an important mechanism of ambient PM2.5 exposure-induced acute heart injury in rats. J Hazard Mater 287C: 392– 401, 2015. 25677476
  23. [29]Li XY, Gilmour PS, Donaldson K, MacNee W Free radical activity and pro-inflammatory effects of particulate air pollution (PM10) in vivo and in vitro. Thorax 51: 1216– 1222, 1996. 8994518 PMC472766
  24. [30]Liu C, Fonken LK, Wang A, Maiseyeu A, Bai Y, Wang TY, Maurya S, Ko YA, Periasamy M, Dvonch T, Morishita M, Brook RD, Harkema J, Ying Z, Mukherjee B, Sun Q, Nelson RJ, Rajagopalan S Central IKKβ inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes. Part Fibre Toxicol 11: 53, 2014. 25358444 PMC4226918
  25. [31]Lomnicki S, Truong H, Vejerano E, Dellinger B Copper oxide-based model of persistent free radical formation on combustion-derived particulate matter. Environ Sci Technol 42: 4982– 4988, 2008. 18678037
  26. [33]Marr LC, Ely MR Effect of air pollution on marathon running performance. Med Sci Sports Exerc 42: 585– 591, 2010. 19952812
  27. [35]Roberts JD, Voss JD, Knight B The association of ambient air pollution and physical inactivity in the United States. PLoS One 9: e90143, 2014. 24598907 PMC3943902
  28. [36]Rundell KW, Caviston R Ultrafine and fine particulate matter inhalation decreases exercise performance in healthy subjects. J Strength Cond Res 22: 2– 5, 2008. 18296948
  29. [37]Russell AP, Foletta VC, Snow RJ, Wadley GD Skeletal muscle mitochondria: a major player in exercise, health and disease. Biochim Biophys Acta 1840: 1276– 1284, 2014. 24291686
  30. [38]Saravia JS, You D, Thevenot P, Lee GI, Shrestha B, Lomnicki S, Cormier SA Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression. Mucosal Immunol 7: 694– 704, 2014. 24172848 PMC3999175
  31. [39]Siegel MP, Kruse SE, Knowels G, Salmon A, Beyer R, Xie H, van Remmen H, Smith SR, Marcinek DJ Reduced coupling of oxidative phosphorylation In Vivo precedes electron transport chain defects due to mild oxidative stress in mice. PLoS One 6: e26963, 2011. 22132085 PMC3222658
  32. [41]Stephenson EJ, Hawley JA Mitochondrial function in metabolic health: a genetic and environmental tug of war. Biochim Biophys Acta 1840: 1285– 1294, 2014. 24345456
  33. [43]Sun Q, Yue P, Deiuliis JA, Lumeng CN, Kampfrath T, Mikolaj MB, Cai Y, Ostrowski MC, Lu B, Parthasarathy S, Brook RD, Moffatt-Bruce SD, Chen LC, Rajagopalan S Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation 119: 538– 546, 2009. 19153269 PMC3845676
  34. [44]Taivassalo T, Jensen TD, Kennaway N, DiMauro S, Vissing J, Haller RG The spectrum of exercise tolerance in mitochondrial myopathies: a study of 40 patients. Brain 126: 413– 423, 2003. 12538407
  35. [45]Thiering E, Cyrys J, Kratzsch J, Meisinger C, Hoffmann B, Berdel D, von Berg A, Koletzko S, Bauer CP, Heinrich J Long-term exposure to traffic-related air pollution and insulin resistance in children: results from the GINIplus and LISAplus birth cohorts. Diabetologia 56: 1696– 1704, 2013. 23666166 PMC3699704
  36. [46]Toshinai K, Mondal MS, Nakazato M, Date Y, Murakami N, Kojima M, Kangawa K, Matsukura S Upregulation of Ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun 281: 1220– 1225, 2001. 11243865
  37. [47]Tschöp MH, Smiley DL, Heiman ML Ghrelin induces adiposity in rodents. Nature 407: 908– 913, 2000. 11057670
  38. [48]Tschöp MH, Speakman JR, Arch JR, Auwerx J, Brüning JC, Chan L, Eckel RH, Farese RV Jr, Galgani JE, Hambly C, Herman MA, Horvath TL, Kahn BB, Kozma SC, Maratos-Flier E, Müller TD, Münzberg H, Pfluger PT, Plum L, Reitman ML, Rahmouni K, Shulman GI, Thomas G, Kahn CR, Ravussin E A guide to analysis of mouse energy metabolism. Nat Methods 9: 57– 63, 2011. 22205519 PMC3654855
  39. [49]Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP, Smith DM, Ghatei MA, Herbert J, Bloom SR A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379: 69– 72, 1996. 8538742
  40. [50]Wang P, Liu J, Li Y, Wu S, Luo J, Yang H, Subbiah R, Chatham J, Zhelyabovska O, Yang Q Peroxisome proliferator-activated receptor {delta} is an essential transcriptional regulator for mitochondrial protection and biogenesis in adult heart. Circ Res 106: 911– 919, 2010. 20075336 PMC2993321
  41. [51]Wang P, Thevenot P, Saravia JS, Ahlert T, Cormier SA Radical-containing particles activate dendritic cells and enhance Th17 inflammation in a mouse model of asthma. Am J Respir Cell Mol Biol 45: 977– 983, 2011. 21493781 PMC3262685
  42. [53]Westbrook DG, Anderson PG, Pinkerton KE, Ballinger SW Perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in non-human primates. Cardiovasc Toxicol 10: 216– 226, 2010. 20668962 PMC2926475
  43. [54]Wilson JL, Enriori PJ A talk between fat tissue, gut, pancreas and brain to control body weight. Mol Cell Endocrinol 418: 108– 119, 2015. 26316427
  44. [55]Xu X, Liu C, Xu Z, Tzan K, Zhong M, Wang A, Lippmann M, Chen LC, Rajagopalan S, Sun Q Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue. Toxicol Sci 124: 88– 98, 2011. 21873646 PMC3196653
  45. [56]Xu Z, Xu X, Zhong M, Hotchkiss IP, Lewandowski RP, Wagner JG, Bramble LA, Yang Y, Wang A, Harkema JR, Lippmann M, Rajagopalan S, Chen LC, Sun Q Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues. Part Fibre Toxicol 8: 20, 2011. 21745393 PMC3152885
  46. [57]Zurlo F, Larson K, Bogardus C, Ravussin E Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest 86: 1423– 1427, 1990. 2243122 PMC296885

Cited by

Sorted by citations

Authors
Stephenson, E. J., Ragauskas, A., Jaligama, S., Redd, J. R., Parvathareddy, J., Peloquin, M. J., Saravia, J., Han, J. C., Cormier, S. A., & Bridges, D.
Affiliations
University of Tennessee Health Science Center (US)
Corresponding author
Bridges, Dave
ORCID
Venue
American Journal of Physiology-Endocrinology and Metabolism
Publisher
American Physiological Society
Published
2016-06-01
Volume
310
Issue
11
Pages
E1003-E1015
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
DOI
10.1152/ajpendo.00521.2015
PMC
PMC4935140
OpenAlex
W2344050926
Cited by
30
References
6
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 6 · 2017: 1 · 2016: 1
FWCI
1.68
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Civil War Book Review (submittedVersion)
Funders
  • Health Science Center, University of Tennessee
  • National Institute of Allergy and Infectious Diseases (R01AI090059)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK107535, P30DK020572)
  • National Institute of Environmental Health Sciences (P42ES013648, R01ES015050)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
environmentally persistent free radicals, prenatal exposure, particulate matter, energy expenditure, skeletal muscle mitochondria, mitochondrial DNA copy number, electron transport chain, citrate synthase, oxidative stress, diet-induced obesity, high-fat diet, offspring body weight, physical activity, developmental programming
MeSH terms
Animals, Dose-Response Relationship, Drug, Energy Metabolism, Environmental Exposure, Environmental Pollutants, Female, Free Radicals, Male, Mice, Inbred C57BL, Mitochondria, Muscle, Pregnancy, Prenatal Exposure Delayed Effects, Mitochondrial Diseases, Mice, Particulate Matter

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