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Cited by 75Birth, Development, and HealthAdipokines, Inflammation, and Metabolic DiseasesGestational Diabetes Research and Management

Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation

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Chang, E., Hafner, H., Varghese, M., Griffin, C., Clemente, J., Islam, M., Carlson, Z., Zhu, A. +4 more·2019·Scientific Reports
DOI 10.1038/s41598-019-52583-xPMC PMC6831633
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Abstract

With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c−) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.

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  • Offspring from obese/high-fat diet-fed mothers often show increased inflammatory marker expression and a higher infiltration of macrophages and other immune cells in their adipose tissue, which may reflect lipotoxicity and likely contributed to the glucose intolerance seen in such offspring.

    “They also often show increased inflammatory marker expression and a higher infiltration of macrophages and other immune cells in their adipose tissue [89, 91, 92], which may reflect lipotoxicity and likely contributed to the glucose intolerance seen in such offspring.”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [92]

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  • There are differences in adipose tissue morphology and leukocyte influx, as well as metabolic phenotype, between exposed male and female offspring.

    “Of the studies that have, there are differences in adipose tissue morphology and leukocyte influx, as well as metabolic phenotype between exposed male and female offspring [92, 96].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [92]

    The Discussion (page not provided) says maternal obesity affected male offspring but not female offspring, supporting a sex difference in metabolic response. The Results on adipose morphology and macrophages (page not provided) examine male offspring only; they do not establish male–female differences in adipose morphology or leukocyte influx. The increased macrophages were predominantly resident CD11c− cells, rather than evidence of greater recruited-cell influx. (LLM, conf=0.87)

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Research works printed but not linked: 47

  1. [1]Heslehurst N Rankin J Wilkinson JR Summerbell CD A nationally representative study of maternal obesity in England, UK: trends in incidence and demographic inequalities in 619 323 births, 1989-2007 Int J Obes (Lond) 2010 34 420 428 10.1038/ijo.2009.250 20029373 · DOI
  2. [2]Nohr EA Combined associations of prepregnancy body mass index and gestational weight gain with the outcome of pregnancy Am J Clin Nutr 2008 87 1750 1759 10.1093/ajcn/87.6.1750 18541565 · DOI
  3. [3]Ng M Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013 Lancet 2014 384 766 781 10.1016/S0140-6736(14)60460-8 24880830 PMC4624264 · DOI · Paper page
  4. [5]Hanks LJ Simpson T McCormick K Casazza K Pediatric obesity prevention: From naive examination of energy imbalance towards strategies that influence the competition for nutrient resources among tissues World J Clin Pediatr 2015 4 50 54 10.5409/wjcp.v4.i4.50 26566477 PMC4637809 · DOI
  5. [7]Dearden L Bouret SG Ozanne SE Sex and gender differences in developmental programming of metabolism Molecular metabolism 2018 15 8 19 10.1016/j.molmet.2018.04.007 29773464 PMC6066743 · DOI
  6. [8]Wankhade UD Thakali KM Shankar K Persistent influence of maternal obesity on offspring health: Mechanisms from animal models and clinical studies Mol Cell Endocrinol 2016 435 7 19 10.1016/j.mce.2016.07.001 27392497 · DOI
  7. [9]Ellsworth L Harman E Padmanabhan V Gregg B Lactational programming of glucose homeostasis: a window of opportunity Reproduction 2018 156 R23 R42 10.1530/REP-17-0780 29752297 PMC6668618 · DOI
  8. [10]Fall CHD Kumaran K Metabolic programming in early life in humans Philos Trans R Soc Lond B Biol Sci 2019 374 20180123 10.1098/rstb.2018.0123 30966889 PMC6460078 · DOI
  9. [12]George LA Different levels of overnutrition and weight gain during pregnancy have differential effects on fetal growth and organ development Reprod Biol Endocrinol 2010 8 75 10.1186/1477-7827-8-75 20576133 PMC2911461 · DOI
  10. [13]Samuelsson AM Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming Hypertension 2008 51 383 392 10.1161/HYPERTENSIONAHA.107.101477 18086952 · DOI · Paper page
  11. [14]Liang C Oest ME Prater MR Intrauterine exposure to high saturated fat diet elevates risk of adult-onset chronic diseases in C57BL/6 mice Birth Defects Res B Dev Reprod Toxicol 2009 86 377 384 10.1002/bdrb.20206 19750488 · DOI
  12. [15]Elahi MM Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice Br J Nutr 2009 102 514 519 10.1017/S000711450820749X 19203419 · DOI
  13. [16]Kral JG Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years Pediatrics 2006 118 e1644 1649 10.1542/peds.2006-1379 17142494 · DOI
  14. [18]Berry DC Stenesen D Zeve D Graff JM The developmental origins of adipose tissue Development 2013 140 3939 3949 10.1242/dev.080549 24046315 PMC3775412 · DOI
  15. [19]Lumeng CN Bodzin JL Saltiel AR Obesity induces a phenotypic switch in adipose tissue macrophage polarization J Clin Invest 2007 117 175 184 10.1172/JCI29881 17200717 PMC1716210 · DOI · Paper page
  16. [21]Barrera C Gatica A Morgan C Obese visceral adipose tissue grafted in lean mice can alter glucose homeostasis and energy efficiency J Biol Regul Homeost Agents 2012 26 411 417 23034260
  17. [22]Greenberg AS Obin MS Obesity and the role of adipose tissue in inflammation and metabolism Am J Clin Nutr 2006 83 461S 465S 10.1093/ajcn/83.2.461S 16470013 · DOI
  18. [23]Spitzer JA Influence of endotoxin on adipose tissue metabolism Adv Exp Med Biol 1972 33 337 344 10.1007/978-1-4684-3228-2_33 4604604 · DOI
  19. [24]Hotamisligil GS Shargill NS Spiegelman BM Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance Science 1993 259 87 91 10.1126/science.7678183 7678183 · DOI · Paper page
  20. [25]Fain JN Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells Vitam Horm 2006 74 443 477 10.1016/S0083-6729(06)74018-3 17027526 · DOI
  21. [26]Kotas ME Medzhitov R Homeostasis, inflammation, and disease susceptibility Cell 2015 160 816 827 10.1016/j.cell.2015.02.010 25723161 PMC4369762 · DOI · Paper page
  22. [28]Monks J Maternal obesity during lactation may protect offspring from high fat diet-induced metabolic dysfunction Nutr Diabetes 2018 8 18 10.1038/s41387-018-0027-z 29695710 PMC5916951 · DOI
  23. [29]Oakberg EF Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium Am J Anat 1956 99 507 516 10.1002/aja.1000990307 13402729 · DOI
  24. [30]Singer K Diet-induced obesity promotes myelopoiesis in hematopoietic stem cells Mol Metab 2014 3 664 675 10.1016/j.molmet.2014.06.005 25161889 PMC4142398 · DOI
  25. [31]Westcott DJ MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity J Exp Med 2009 206 3143 3156 10.1084/jem.20091333 19995956 PMC2806469 · DOI
  26. [32]Lumeng CN DelProposto JB Westcott DJ Saltiel AR Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes Diabetes 2008 57 3239 3246 10.2337/db08-0872 18829989 PMC2584129 · DOI
  27. [33]Griffin C TLR4, TRIF, and MyD88 are essential for myelopoiesis and CD11c J Biol Chem 2018 293 8775 8786 10.1074/jbc.RA117.001526 29636416 PMC5995515 · DOI
  28. [34]Singer K Neuropeptide Y is produced by adipose tissue macrophages and regulates obesity-induced inflammation PLoS One 2013 8 e57929 10.1371/journal.pone.0057929 23472120 PMC3589443 · DOI
  29. [35]Morris DL Oatmen KE Wang T DelProposto JL Lumeng CN CX3CR1 deficiency does not influence trafficking of adipose tissue macrophages in mice with diet-induced obesity Obesity (Silver Spring) 2012 20 1189 1199 10.1038/oby.2012.7 22252034 PMC4006981 · DOI
  30. [36]Jensen TL Kiersgaard MK Sørensen DB Mikkelsen LF Fasting of mice: a review Lab Anim 2013 47 225 240 10.1177/0023677213501659 24025567 · DOI
  31. [37]Gluckman PD Hanson MA Developmental origins of disease paradigm: a mechanistic and evolutionary perspective Pediatr Res 2004 56 311 317 10.1203/01.PDR.0000135998.08025.FB 15240866 · DOI · Paper page
  32. [38]Freedland ES Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review Nutr Metab (Lond) 2004 1 12 10.1186/1743-7075-1-12 15530168 PMC535537 · DOI
  33. [39]Ibrahim MM Subcutaneous and visceral adipose tissue: structural and functional differences Obes Rev 2010 11 11 18 10.1111/j.1467-789X.2009.00623.x 19656312 · DOI · Paper page
  34. [40]Thompson MD Enhanced Steatosis and Fibrosis in Liver of Adult Offspring Exposed to Maternal High-Fat Diet Gene Expr 2016 17 47 59 10.3727/105221616X692135 27342733 PMC5611859 · DOI
  35. [41]Lopez-Soldado I Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model Diabetes 2015 64 796 807 10.2337/db14-0728 25277398 · DOI
  36. [42]Irimia JM Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice J Biol Chem 2017 292 10455 10464 10.1074/jbc.M117.786525 28483921 PMC5481557 · DOI
  37. [44]Moraes-Vieira PM RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance Cell Metab 2014 19 512 526 10.1016/j.cmet.2014.01.018 24606904 PMC4078000 · DOI
  38. [46]Singer K Differences in Hematopoietic Stem Cells Contribute to Sexually Dimorphic Inflammatory Responses to High Fat Diet-induced Obesity J Biol Chem 2015 290 13250 13262 10.1074/jbc.M114.634568 25869128 PMC4505578 · DOI
  39. [47]Varghese M Sex Differences in Inflammatory Responses to Adipose Tissue Lipolysis in Diet-Induced Obesity Endocrinology 2019 160 293 312 10.1210/en.2018-00797 30544158 PMC6330175 · DOI
  40. [48]Yang Y Smith DL Jr. Keating KD Allison DB Nagy TR Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J mice Obesity (Silver Spring) 2014 22 2147 2155 10.1002/oby.20811 24942674 PMC4180788 · DOI
  41. [49]Rosenfeld CS Sex-Specific Placental Responses in Fetal Development Endocrinology 2015 156 3422 3434 10.1210/en.2015-1227 26241064 PMC4588817 · DOI
  42. [50]Myatt L Thornburg KL Effects of Prenatal Nutrition and the Role of the Placenta in Health and Disease Methods Mol Biol 2018 1735 19 46 10.1007/978-1-4939-7614-0_2 29380305 · DOI
  43. [51]Einstein FH Accretion of visceral fat and hepatic insulin resistance in pregnant rats Am J Physiol Endocrinol Metab 2008 294 E451 455 10.1152/ajpendo.00570.2007 18073320 · DOI
  44. [52]Stuebe AM Rich-Edwards JW The reset hypothesis: lactation and maternal metabolism Am J Perinatol 2009 26 81 88 10.1055/s-0028-1103034 19031350 PMC3006166 · DOI
  45. [53]Upadhyay A Time-restricted feeding reduces high-fat diet associated placental inflammation and limits adverse effects on fetal organ development Biochem Biophys Res Commun 2019 514 415 421 10.1016/j.bbrc.2019.04.154 31053302 · DOI
  46. [54]Mayor RS Maternal high-fat diet is associated with impaired fetal lung development Am J Physiol Lung Cell Mol Physiol 2015 309 L360 368 10.1152/ajplung.00105.2015 26092997 PMC4538234 · DOI
  47. [55]Heerwagen MJ Stewart MS de la Houssaye BA Janssen RC Friedman JE Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice PLoS One 2013 8 e67791 10.1371/journal.pone.0067791 23825686 PMC3692451 · DOI

Cited by

Sorted by citations

Authors
Chang, E., Hafner, H., Varghese, M., Griffin, C., Clemente, J., Islam, M., Carlson, Z., Zhu, A., Hak, L., Abrishami, S., Gregg, B., & Singer, K.
Affiliations
University of Michigan (US)
Corresponding author
Singer, K.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-11-05
Volume
9
Issue
1
Pages
16027-16027
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-52583-x
PMC
PMC6831633
OpenAlex
W2983129453
Cited by
75
References
8
Citations by year
2026: 5 · 2025: 4 · 2024: 13 · 2023: 6 · 2022: 20 · 2021: 14 · 2020: 13
FWCI
12.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • University of Michigan (P30CA046592)
  • Endocrine Fellows Foundation
  • National Institutes of Health (NIH T32, DK071212)
  • National Cancer Institute (P30CA046592)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K08DK101755, U2CDK110768, R01DK115583, K08DK102526, P30DK020572, T32DK071212)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Keywords
maternal obesity, gestational obesity, developmental programming, offspring adiposity, adipose tissue inflammation, adipose tissue macrophages, glucose tolerance, high-fat diet, body composition, liver mass, sex differences, metabolic inflammation
MeSH terms
Animals, Body Weight, Female, Glucose Tolerance Test, Glycerol, Liver, Macrophages, Male, Metabolic Diseases, Mice, Inbred C57BL, Obesity, Pregnancy, Prenatal Exposure Delayed Effects, Triglycerides, CD11c Antigen, Subcutaneous Fat, Mice, Diet, High-Fat

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