The Early Origins of Obesity and Insulin Resistance: Timing, Programming and Mechanisms
Open accessAbstract
Maternal obesity is associated with an increased risk of developing gestational diabetes mellitus and it also results in an increased risk of giving birth to a large baby with increased fat mass. Furthermore, it is also contributes to an increased risk of obesity and insulin resistance in the offspring in childhood, adolescence and adult life. It has been proposed that exposure to maternal obesity may therefore result in an 'intergenerational cycle' of obesity and insulin resistance. There is significant interest in whether exposure to maternal obesity around the time of conception alone contributes directly to poor metabolic outcomes in the offspring and whether dieting in the obese mother before pregnancy or around the time of conception has metabolic benefits for the offspring. This review focusses on experimental and clinical studies that have investigated the specific impact of exposure to maternal obesity during the periconceptional period alone or extending beyond conception on adipogenesis, lipogenesis and on insulin signalling pathways in the fat, liver and muscle of the offspring. Findings from these studies highlight the need for a better evidence base for the development of dietary interventions in obese women before pregnancy and around the time of conception to maximize the metabolic benefits and minimize the metabolic costs for the next generation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Female subjects seem to have greater protection against the adverse effects of lipo-toxicity caused by dysfunctional adipose tissue, probably through a differentiated expression of sex-dependent genes involved in adipogenesis.
“Moreover, it has been noted that female subjects seem to have greater protection against the adverse effects of lipo-toxicity caused by dysfunctional adipose tissue, probably through a differentiated expression of sex-dependent genes involved in adipogenesis (Figure 2) [58,82,83].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [83]
Cites
Critical nodes in signalling pathways: insights into insulin action
Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1837 · Cited by 2,760 · see citing works
Ogden, C. L., Yanovski, S. Z., Carroll, M. D., & Flegal, K. M. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.052 · Cited by 1,561 · see citing works
MicroRNAs 103 and 107 regulate insulin sensitivity
Trajkovski, M., Hausser, J., Soutschek, J., Bhat, B., Akin, A., Zavolan, M., Heim, M. H., & Stoffel, M. (2011) · Nature · doi:10.1038/nature10112 · Cited by 1,000 · see citing works
Effects of Maternal Surgical Weight Loss in Mothers on Intergenerational Transmission of Obesity
Smith, J., Cianflone, K., Biron, S., Hould, F. S., Lebel, S., Marceau, S., Lescelleur, O., Biertho, L., Simard, S., Kral, J. G., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0709 · Cited by 354 · see citing works
Oben, J. A., Mouralidarane, A., Samuelsson, A.-M., Matthews, P. J., Morgan, M. L., Mckee, C., Soeda, J., Fernandez-Twinn, D. S., Martin-Gronert, M. S., Ozanne, S. E., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2009.12.042 · Cited by 314 · see citing works
Self-citationTaylor, P. D., McConnell, J., Khan, I. Y., Holemans, K., Lawrence, K. M., Asare-Anane, H., Persaud, S. J., Jones, P. M., Petrie, L., Hanson, M. A., et al. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00355.2004 · Cited by 297 · see citing works
Maternal adiposity—a determinant of perinatal and offspring outcomes?
Lawlor, D. A., Relton, C., Sattar, N., & Nelson, S. M. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.176 · Cited by 192 · see citing works
Stanford, K. I., Lee, M.-Y., Getchell, K. M., So, K., Hirshman, M. F., & Goodyear, L. J. (2015) · Diabetes · doi:10.2337/db13-1848 · Cited by 151 · see citing works
Murabayashi, N., Sugiyama, T., Zhang, L., Kamimoto, Y., Umekawa, T., Ma, N., & Sagawa, N. (2013) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2013.02.003 · Cited by 114 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Origins of lifetime health around the time of conception: causes and consequences
Fleming, T. P., Watkins, A. J., Velazquez, M. A., Mathers, J. C., Prentice, A. M., Stephenson, J., Barker, M., Saffery, R., Yajnik, C. S., Eckert, J. J., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30312-x · Cited by 1,147 · see citing works
Warland, J., Dorrian, J., Morrison, J. L., & O'Brien, L. M. (2018) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2018.03.004 · Cited by 224 · see citing works
Self-citationGaillard, R., & Jaddoe, V. W. V. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00869-z · Cited by 34 · see citing works
Schiera, G., Macajone, G., Volpes, S., Greco, L., Di Liegro, C. M., Serio, G., Caradonna, F., & Naselli, F. (2026) · Cells · doi:10.3390/cells15040366 · Cited by 8 · see citing works
- Authors
- Nicholas, L. M., Morrison, J. L., Rattanatray, L., Zhang, S., Ozanne, S. E., & McMillen, I. C.
- Affiliations
- University of South Australia (AU)
- University of Cambridge (GB)
- Corresponding author
- Nicholas, L M
- Venue
- International Journal of Obesity
- Published
- 2015-09-14
- Volume
- 40
- Issue
- 2
- Pages
- 229-238
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2236727832
- Cited by
- 146
- References
- 9
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 5 · 2023: 16 · 2022: 7 · 2021: 13 · 2020: 13 · 2019: 25 · 2018: 15 · 2017: 15 · 2016: 20 · 2015: 2 · 2014: 1
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, other-oa)
- UniSA Research Outputs Repository (University of South Australia) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- British Heart Foundation (FS/09/029/27902)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- maternal obesity, insulin resistance, gestational diabetes mellitus, periconceptional period, intergenerational programs, offspring obesity, adipogenesis, lipogenesis, insulin signaling, fetal programming
- MeSH terms
- Adult, Female, Humans, Infant, Insulin Resistance, Mothers, Obesity, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Risk Factors, Signal Transduction, Diabetes, Gestational, Maternal Nutritional Physiological Phenomena, Pediatric Obesity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
