Developmental programming by maternal obesity alters offspring lifespan and immune responses in a diet- and sex-specific manner

Cells and Development, vol. 183, pp. 204040

Abstract

Maternal obesity is a growing health concern that predisposes offspring to metabolic dysfunction, immune system alterations, and neurodegenerative disorders. To investigate the intergenerational effects of maternal obesity, we used Drosophila melanogaster exposed to high-sugar (HSD) and high-fat diets (HFD) before mating. We found that maternal diet-induced obesity significantly altered offspring lifespan, immune responses, and neuronal health in a sex- and diet-specific manner. Male offspring were particularly susceptible, exhibiting reduced lifespan, impaired climbing ability, and increased axonal degeneration, especially following maternal HFD exposure. Transcriptomic analyses revealed age-dependent and diet-specific changes, with males showing pronounced alterations at 50 days of age. Developmental programming of hemocytes (blood-like cells) played a crucial role in these outcomes, as knockdown of key immune pathways such as Relish and upd3 in hemocytes further influenced lifespan in a diet-specific manner. These findings highlight the complex interplay between maternal diet and immune function, underscoring the impact of maternal obesity-induced imprinting on immune cells and subsequent long-term health consequences. Our study provides new insights into conserved mechanisms linking maternal metabolic health to offspring outcomes and emphasizes the continued need for animal models to understand intergenerational health impacts.

Authors 11

1. Seyhmus Bayar

   University of Bonn

   Affiliation as printed

   Developmental Biology of the Immune System, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany

2. Lea Seep

   University of Bonn

   Affiliation as printed

   Computational Life Sciences, Life & Medical Sciences (LIMES) Institute and Bonn Center for Mathematical Life Sciences, University of Bonn, 53115 Bonn, Germany

3. Karolína Doubková Aachen Institute for Developmental Biology

   German Center for Neurodegenerative Diseases · RWTH Aachen University

   Affiliation as printed

   German Center for Neurodegenerative Diseases (DZNE), Dynamics of Neuronal Circuits Group, 53127 Bonn, Germany; Institute for Developmental Biology, RWTH Aachen University, Aachen 52074, Germany

   German Center for Neurodegenerative Diseases (DZNE), Dynamics of Neuronal Circuits Group, 53127 Bonn, Germany; Institute for Developmental Biology, RWTH Aachen, Aachen 352074, Germany

4. Jelena Zurkovic

   University of Bonn

   Affiliation as printed

   Biochemistry & Cell Biology of Lipids, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany

5. Margret Helene Bülow

   University of Bonn

   Affiliation as printed

   Neuronal Cell Metabolism, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany

6. Katrin Kierdorf

   University of Freiburg

   Affiliation as printed

   Institute for Infection Prevention and Control, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; CIBSS-Center for Integrative Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany

7. Reinhard Bauer

   University of Bonn

   Affiliation as printed

   Department of Molecular Developmental Biology, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany

8. Christoph Thiele

   University of Bonn

   Affiliation as printed

   Biochemistry & Cell Biology of Lipids, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany

9. Gaia Tavosanis Aachen Institute for Developmental Biology

   German Center for Neurodegenerative Diseases · RWTH Aachen University

   Affiliation as printed

   German Center for Neurodegenerative Diseases (DZNE), Dynamics of Neuronal Circuits Group, 53127 Bonn, Germany; Institute for Developmental Biology, RWTH Aachen University, Aachen 52074, Germany

   German Center for Neurodegenerative Diseases (DZNE), Dynamics of Neuronal Circuits Group, 53127 Bonn, Germany; Institute for Developmental Biology, RWTH Aachen, Aachen 352074, Germany

10. Jan Hasenauer

    University of Bonn

    Affiliation as printed

    Computational Life Sciences, Life & Medical Sciences (LIMES) Institute and Bonn Center for Mathematical Life Sciences, University of Bonn, 53115 Bonn, Germany

11. Elvira Mass corresponding

    University of Bonn

    Affiliation as printed

    Developmental Biology of the Immune System, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany. Electronic address: elvira.mass@uni-bonn.de