Open AccessExercise-induced 3′-sialyllactose in breast milk is a critical mediator to improve metabolic health and cardiac function in mouse offspring
Author(s) -
Johan E. Harris,
Kelsey M. Pinckard,
Katherine R. Wright,
Lisa A. Baer,
Peter J. Arts,
Eaman Abay,
Vikram Shettigar,
Adam C. Lehnig,
Bianca Robertson,
Kendra L Madaris,
Tyler J. Canova,
Clark Sims,
Laurie J. Goodyear,
Aline Andres,
Mark T. Ziolo,
Lars Bode,
Kristin I. Stanford
Publication year - 2020
Publication title -
nature metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.834
H-Index - 22
ISSN - 2522-5812
DOI - 10.1038/s42255-020-0223-8
Subject(s) - offspring , overnutrition , lactation , pregnancy , type 2 diabetes , endocrinology , obesity , medicine , physiology , disease , cardiac function curve , diabetes mellitus , biology , heart failure , genetics
Poor maternal environments, such as under- or overnutrition, can increase the risk for the development of obesity, type 2 diabetes and cardiovascular disease in offspring 1-9 . Recent studies in animal models have shown that maternal exercise before and during pregnancy abolishes the age-related development of impaired glucose metabolism 10-15 , decreased cardiovascular function 16 and increased adiposity 11,15 ; however, the underlying mechanisms for maternal exercise to improve offspring's health have not been identified. In the present study, we identify an exercise-induced increase in the oligosaccharide 3'-sialyllactose (3'-SL) in milk in humans and mice, and show that the beneficial effects of maternal exercise on mouse offspring's metabolic health and cardiac function are mediated by 3'-SL. In global 3'-SL knockout mice (3'-SL -/- ), maternal exercise training failed to improve offspring metabolic health or cardiac function in mice. There was no beneficial effect of maternal exercise on wild-type offspring who consumed milk from exercise-trained 3'-SL -/- dams, whereas supplementing 3'-SL during lactation to wild-type mice improved metabolic health and cardiac function in offspring during adulthood. Importantly, supplementation of 3'-SL negated the detrimental effects of a high-fat diet on body composition and metabolism. The present study reveals a critical role for the oligosaccharide 3'-SL in milk to mediate the effects of maternal exercise on offspring's health. 3'-SL supplementation is a potential therapeutic approach to combat the development of obesity, type 2 diabetes and cardiovascular disease.