Maternal Brown Fat Thermogenesis Programs Glucose Tolerance in the Male Offspring
Rebecca Oelkrug,
Christin Krause,
Beate Herrmann,
Julia Resch,
Sogol Gachkar,
Alexander T. El Gammal,
Stefan Wolter,
Oliver Mann,
Henrik Oster,
Henriette Kirchner,
Jens Mittag
Affiliations
Rebecca Oelkrug
Institute for Endocrinology and Diabetes–Molecular Endocrinology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany
Christin Krause
Institute for Human Genetics–Epigenetics and Metabolism, Deutsches Zentrum für Diabetesforschung, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany
Beate Herrmann
Institute for Endocrinology and Diabetes–Molecular Endocrinology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany
Julia Resch
Institute for Endocrinology and Diabetes–Molecular Endocrinology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany
Sogol Gachkar
Institute for Endocrinology and Diabetes–Molecular Endocrinology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany
Alexander T. El Gammal
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Stefan Wolter
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Oliver Mann
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Henrik Oster
Institute of Neurobiology, University of Lübeck, 23562 Lübeck, Germany
Henriette Kirchner
Institute for Human Genetics–Epigenetics and Metabolism, Deutsches Zentrum für Diabetesforschung, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany
Jens Mittag
Institute for Endocrinology and Diabetes–Molecular Endocrinology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany; Corresponding author
Summary: Environmental temperature is a driving factor in evolution, and it is commonly assumed that metabolic adaptations to cold climates are the result of transgenerational selection. Here, we show in mice that even minor changes in maternal thermogenesis alter the metabolic phenotype already in the next generation. Male offspring of mothers genetically lacking brown adipose tissue (BAT) thermogenesis display increased lean mass and improved glucose tolerance as adults, while females are unaffected. The phenotype is replicated in offspring of mothers kept at thermoneutrality; conversely, mothers with higher gestational BAT thermogenesis produce male offspring with reduced lean mass and impaired glucose tolerance. Running-wheel exercise reverses the offspring’s metabolic impairments, pointing to the muscle as target of these fetal programming effects. Our data demonstrate that gestational BAT activation negatively affects metabolic health of the male offspring; however, these unfavorable fetal programming effects may be negated by active lifestyle.
