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Cited by 28Birth, Development, and HealthAdipose Tissue and MetabolismLipid metabolism and biosynthesis

Maternal High-Fat Diet Programs White and Brown Adipose Tissue Lipidome and Transcriptome in Offspring in a Sex- and Tissue-Dependent Manner in Mice

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Savva, Christina, Helguero, Luisa A., González-Granillo, Marcela, Melo, Tânia, Couto, Daniela, Buyandelger, Byambajav, Gustafsson, Sonja, Liu, Jianping +3 more·2022·International Journal of Obesity
DOI 10.1038/s41366-021-01060-5PMC PMC8960419

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Abstract

Objective: The prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring. Methods: Mice dam were fed either a control diet or a high-fat diet (HFD) for 6-week prior mating and continued their respective diet during gestation and lactation. At weaning, female and male offspring were fed the HFD until sacrifice. White (WAT) and brown (BAT) adipose tissues were investigated in vivo by nuclear magnetic resonance at two different timepoints in life (midterm and endterm) and tissues were collected at endterm for lipidomic analysis and RNA sequencing. We explored the sex-dependent metabolic adaptation and gene programming changes by maternal HFD in visceral AT (VAT), subcutaneous AT (SAT) and BAT of offspring. Results: We show that the triglyceride profile varies between adipose depots, sexes and maternal diet. In female offspring, maternal HFD remodels the triglycerides profile in SAT and BAT, and increases thermogenesis and cell differentiation in BAT, which may prevent metabolic complication later in life. Male offspring exhibit whitening of BAT and hyperplasia in VAT when born from high-fat mothers, with impaired metabolic profile. Maternal HFD differentially programs gene expression in WAT and BAT of female and male offspring. Conclusion: Maternal HFD modulates metabolic profile in offspring in a sex-dependent manner. A sex- and maternal diet-dependent gene programming exists in VAT, SAT, and BAT which may be key player in the sexual dimorphism in the metabolic adaptation later in life.

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  • In mice, maternal high-fat diet offspring showed increased fasting glycemia regardless of sex compared to control offspring, and this increase was more evident in male offspring.

    “Analysis showed a predictable increase in glycemia in mo-HF offspring regardless of sex, compared to mo-C offspring; this increase was more evident in M-moHF.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [82]

    Table 1 in the Results (page unavailable) reports lower fasting glucose in female moHF offspring than in female moC offspring at both timepoints, contrary to the claimed increase regardless of sex. Male moHF offspring had higher mean glucose than male moC offspring, but the table does not mark either within-sex glucose comparison as statistically significant. (LLM, conf=0.90)

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  • In mice, maternal high-fat diet offspring had increased body weight at 5 weeks compared to control offspring, and this increase was more evident in males.

    “At the age of 5 weeks, offspring body weight was sex- and maternal diet-dependent; offspring of mo-HFD mothers increased in weight compared to offspring of mo-CD, and this increase was more evident in male offspring (M-moHF) compared to female offspring (F-moHF).”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [82]

    The Results section (page unavailable) says offspring body weight at weaning was sex- and maternal-diet-dependent, and the Discussion says maternal high-fat diet altered male offspring weight at weaning. But the Methods date weaning at 3 weeks, not 5; the text does not establish the claimed increase over controls at age 5 weeks or that the increase was greater in males. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • 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 [82]

    The Discussion (page not provided) proposes a protective mechanism in female mouse offspring of obese mothers, compared with males, and describes sex-dependent expression of genes involved in adipogenesis. It says the precise mechanism remains unresolved. The claim extends those findings to female subjects generally and specifically to protection from lipotoxicity caused by dysfunctional adipose tissue, which the cited passages do not establish. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Female offspring of mo-HFD mothers showed a higher percentage of body fat compared to male offspring of mo-HFD mothers.

    “Female offspring showed a higher percentage of body fat compared to M-moHF.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [82]

    The Results section (page unavailable) reports that females had more total fat than males at endterm, and the Fig. 1 caption identifies total fat as a percentage of body weight. The text does not explicitly establish that this difference holds specifically between female and male offspring of high-fat-diet mothers, nor does it report the difference at other time points. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Prenatal exposure to maternal obesity can modulate offspring adipose tissue programming in a sex-dependent way.

    “Savva C. et al. investigated how prenatal exposure to maternal obesity can modulate offspring adipose tissue programming in a sex-dependent way [82].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [82]

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Cited by

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Authors
Savva, C., Helguero, L. A., González-Granillo, M., Melo, T., Couto, D., Buyandelger, B., Gustafsson, S., Liu, J., Domingues, M. R., Li, X., & Korach-André, M.
Affiliations
  • Karolinska University Hospital (SE)
  • University of Aveiro (PT)
  • Centro de Estudos do Ambiente e do Mar (PT)
Corresponding author
Korach-André, Marion
ORCID
Venue
International Journal of Obesity
Publisher
Springer Science and Business Media LLC
Published
2022-01-07
Volume
46
Issue
4
Pages
831-842
ISSN
  • 0307-0565 (ISSN-L)
  • 1476-5497
DOI
10.1038/s41366-021-01060-5
PMC
PMC8960419
OpenAlex
W4205781664
Cited by
28
References
1
Citations by year
2026: 1 · 2025: 7 · 2024: 8 · 2023: 4 · 2022: 8
FWCI
7.40
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Obesity (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • AstraZeneca
  • Indiana Corn Marketing Council
  • Novo Nordisk
  • Novo Nordisk Fonden (NNF14OC0010705)
  • Rede de Química e Tecnologia (UIDB/50006/2020, UIDB/04501/2020)
  • Laboratório Associado para a Química Verde (CENTRO-01-0145-FEDER-000003, UIDB/04501/2020, UIDB/50017/2020, UID/QUI/00062/2019, UIDB/50006/2020, UIDP/50017)
  • Centro de Estudos Ambientais e Marinhos, Universidade de Aveiro (UIDP/50017/2020, 50017, UID/QUI/00062/2019, UIDB / 50017/2020, UIDB/50006/2020, UIDP/50017/2020+UIDB/ 50017/2020)
  • Fundação para a Ciência e a Tecnologia (CENTRO-01-0246-FEDER-000018, 01-0145, UIDP/50017/2020 + UIDB/50017/2020, CENTRO-01-0145-FEDER, CESAM,UIDP/50017/2020, UID/QUI/00062/2019, CENTRO-01-0145-FEDER- 000003, UIDB/50017/2020, FCT UID/QUI/00062/ 2019, UIDB/04501/2020, UID/BIM/04501/2020, UIDP/50017/2020, UIDB/50006/2020)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
maternal high-fat diet, fetal nutrition, white adipose tissue, brown adipose tissue, adipose tissue transcriptome, sex differences, visceral adipose tissue, subcutaneous adipose tissue, thermogenesis, adipogenesis, adipose tissue hyperplasia
MeSH terms
Lipidomics, Animals, Adipose Tissue, Brown, Female, Humans, Male, Pregnancy, Thermogenesis, Mice, Adipose Tissue, White, Diet, High-Fat, Transcriptome

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