1664-P: High Fat High Sucrose Exposure during Lactation but Not during the Post-Weaning Period Programs Impaired Glucose Homeostasis

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. At the age of 12 weeks, 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. Preliminary data suggests that increased adipose tissue inflammation might be mechanistically involved in impaired glucose tolerance of lactation 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 the most critical in terms of metabolic programing. Disclosure A.Goergen: None. S.Wueest: None. D.Konrad: Research Support; Novo Nordisk A/S.