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Session: Diet, Body Size, and Diabetes in Pregnancy: Impact on Offspring Metabolic Health (Oral 12)

(OR12-05-23) The Impact of Maternal Protein Restriction and High-Fat Diet in Offspring on the Outcomes of Growth Hormone Treatment in Mice

Sunday, July 23, 2023
4:48 PM – 5:00 PM ET
Location:  Constitution A

    Presenting Author(s)

  • Obin Kwon, MD PhD

    Assistant Professor
    Seoul National University College of Medicine
    Seoul, Seoul-t'ukpyolsi, Republic of Korea

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • HK

    Hanbin Kim

    Seoul National University College of Medicine

  • BK

    Bohye Kim

    Seoul National University College of Medicine

  • YL

    Yoojin Lee

    Seoul National University College of Medicine

  • HM

    Hyeon Seok Moon

    Seoul National University College of Medicine

  • JK

    Jae Hyun Kim

    Seoul National University Bundang Hospital

Disclosure(s):
Obin Kwon, MD PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Small for gestational age (SGA) offspring has a higher risk of developing metabolic disorders in adulthood. SGA children who have not caught up can receive growth hormone (GH) therapy. This treatment has raised concerns that it may increase the risk of diabetes because GH is one of the counterregulatory hormones for insulin, but this has not been investigated in randomized clinical trials. In this study, we aimed to evaluate the outcomes of GH treatment on the growth and glucose metabolism of SGA mice offspring made by a maternal protein restriction. We also checked whether feeding offspring the high-fat diet would alter those outcomes.

Methods: Pregnant C57BL/6 mice were fed a normal chow diet (NCD) or protein-restricted diet (PRD; 9 kcal% protein) during pregnancy and lactation periods. SGA pups from PRD-fed dam were divided into GH-treated (from weaning until 8-week-old) group or vehicle-treated group. Body weight and nose-to-anus length were serially measured. Glucose homeostasis were evaluated by glucose tolerance test in adulthood. In the high-fat diet (HFD) trial, all of the offspring were given HFD (60 kcal% fat) starting at 8 weeks of age, and same parameters mentioned above were assessed.

Results: SGA group showed less body weight and length at birth and 3 weeks compared to NCD-fed controls. Vehicle-treated SGA offspring was shorter than control in adulthood, which could be partially recovered by GH treatment. GH treatment had no significant effect on body weight in SGA offspring. Glucose tolerance was impaired in adulthood in SGA group, which showed trends of improvement by GH treatment. Catch-up growth by GH treatment was inhibited by HFD feeding, but no metabolic parameters were disturbed by GH treatment.

Conclusions: Maternal protein restriction led offspring to smaller body size and dysregulated glucose metabolism, which all could be rescued by GH treatment. These results suggest that GH treatment may not, at least, deteriorate glucose metabolism in SGA offspring. It may be important to keep balanced diet for the efficacy of GH treatment.

Funding Sources: This work was supported by grant no 16-2018-010 from the SNUBH Research Fund and the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (No. 2020R1A4A3078962 and 2020R1C1C1008033).