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Maternal high-fat diet up-regulates type-1 cannabinoid receptor with estrogen signaling changes in a sex- and depot- specific manner in white adipose tissue of adult rat offspring

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Abstract

Purpose

Obesity and high-fat (HF) diet are associated with over activation of the endocannabinoid system (ECS). We have demonstrated that maternal HF diet induces early obesity and modulates cannabinoid signaling in visceral (VIS) and subcutaneous (SUB) white adipose tissue (WAT) in weanling rat offspring. We hypothesized that perinatal maternal HF diet would program the expression of ECS in adipose tissue in a long-term way in parallel to alterations in epigenetic markers and sex hormone signaling.

Methods

Progenitor female rats received control diet (C, 9% fat) or isocaloric high-fat diet (HF, 28% fat) for 8 weeks before mating, gestation, and lactation. All pups were weaned to C diet and they were euthanized at 180 days old.

Results

Maternal HF diet induced overweight and increased SUB WAT mass of male and female adult offspring. Maternal HF diet induced hypertrophy of VIS and SUB adipocytes only in female offspring associated with increased type 1 cannabinoid receptor protein (CB1) and mRNA (Cnr1) levels. These changes were associated with increased estrogen receptor α binding to Cnr1 promoter in SUB WAT of adult female offspring, which may contribute to higher expression of Cnr1.

Conclusion

Increased CB1 signaling in adipose tissue might contribute to higher adiposity programmed by maternal HF diet because endocannabinoids stimulate the accumulation of fat in the adipose tissue. Our findings provide molecular insights into sex-specific targets for anti-obesity therapies based on the endocannabinoid system.

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Acknowledgements

We would like to thank Luela Dias and Juliana Penna for the technical support.

Funding

This work was supported by the Carlos Chagas Filho Research Foundation of the State of Rio de Janeiro (FAPERJ) (Grant No. E-26/202.816/2015), Brazil, National Council for Scientific and Technological Development (CNPq) (Grant No. 797473807/2013-0), Brazil, Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil, and National Institutes Health (Grant No. DK084036), United States.

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Authors and Affiliations

  1. Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Mariana Macedo de Almeida, Camilla P. Dias-Rocha, Clara F. Reis-Gomes, Aline Cordeiro, Carmen C. Pazos-Moura & Isis H. Trevenzoli

  2. Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

    Haimei Wang & Lisa Joss-Moore

  3. Laboratory of Molecular Endocrinology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, Rio de Janeiro, 21941-902, Brazil

    Mariana Macedo de Almeida

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  1. Mariana Macedo de Almeida
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MMA, CPD-R and CFR-G have participated in animal experiments, collection and interpretation of data. MMA, HW and LJ-M contributed with the chromatin immunoprecipitation assays. IHT, CCP-M, AC delineated the experimental design and supervised the study. MMA, LJ-M and IHT have written the manuscript.

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Correspondence to Mariana Macedo de Almeida.

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de Almeida, M.M., Dias-Rocha, C.P., Reis-Gomes, C.F. et al. Maternal high-fat diet up-regulates type-1 cannabinoid receptor with estrogen signaling changes in a sex- and depot- specific manner in white adipose tissue of adult rat offspring. Eur J Nutr 60, 1313–1326 (2021). https://doi.org/10.1007/s00394-020-02318-w

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