High fat high sucrose exposure during lactation but not during the post-weaning period programs impaired glucose homeostasis

Goergen, A.; Konrad, D.; Borsigova, M.; Wueest, S.

doi:10.1101/2025.01.15.633246

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bioRxiv · 10.1101/2025.01.15.633246

High fat high sucrose exposure during lactation but not during the post-weaning period programs impaired glucose homeostasis

Goergen, A.·Konrad, D.·Borsigova, M.·Wueest, S.

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Abstract

Nutrition during critical developmental windows plays a pivotal role in shaping long-term metabolic health. Exposure to a Western diet in early life may lead to altered metabolic programing, potentially influencing the risk to develop obesity and type 2 diabetes. In particular, an early exposure to an obesogenic diet may induce a metabolic program that only emerges upon dietary challenges later in life. Accordingly, understanding the long-term impact of nutritional insults in different stages of early life may provide strategies for primary prevention. Therefore, the present study aimed to determine which time window in the post-natal period is most critical for long-term metabolic health. To this end, pups born to lean mouse dams were exposed to a high-fat, high-sucrose (HFHS) diet for 3 weeks during lactation or in the post-weaning period. Thereafter, mice were either fed a regular chow diet until the age of 30 weeks or exposed to a second bout of HFHS diet for the last 12 weeks. Metabolic health and development of obesity was assessed by regular monitoring of glucose homeostasis and body weight gain. 12 week-old mice with lactational exposure to a HFHS diet revealed a significantly impaired glucose tolerance compared to control mice, while glucose tolerance of post -weaning exposed mice was similar to the control group. Moreover, a second bout of HFHS diet impaired glucose tolerance and increased body and adipose tissue weight in mice with lactational exposure to a significant greater extent than in post-weaning exposed mice. Hence, exposure to HFHS during lactation but not during the post-weaning period programs impaired glucose homeostasis, suggesting that the lactational window may be more critical in terms of metabolic programing.

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Goergen, A., Konrad, D., Borsigova, M., Wueest, S.. 2025-01-19. High fat high sucrose exposure during lactation but not during the post-weaning period programs impaired glucose homeostasis. https://doi.org/10.1101/2025.01.15.633246

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