THU302 Protective Effects Of Lactation On Maternal Metabolism

Disclosure: J.R. Hens: None. Y. Ding: None. S. Brown: None. H. Song: None. J.J. Wysolmerski: None. R. Belfort De Aguiar: None. A history of lactation significantly lowers the risk of developing Type 2 diabetes (T2D) by almost 50%. However, little is known about how milk production durably changes maternal metabolism. We hypothesized that lactation protects against diabetes by improving maternal glucose metabolism. Changes in body composition, glucose metabolism, insulin secretion and tissue triglyceride levels were measured in age-matched cohorts of mice that lactated (L) or did not lactate but went through a pregnancy (NL); age-matched virgins served as controls (V). L and NL mice were studied 4 weeks after weaning of pups from the L group. An euglycemic-hyperinsulinemic clamp was used to further examine glucose metabolism. Multiple rounds of lactation were examined to determine if body composition or glucose metabolism changed with repeated cycles of reproduction. Liver weight was higher in L mice when compared to V mice. Liver triglycerides were lower in L and NL mice when compared to V mice. Circulating fasting levels of plasma free fatty acids were unchanged between the three groups. Perigonadal fat trended higher in NL mice compared to L and V mice after one round of lactation. However, after two rounds of lactation, NL mice had significantly more perigonadal fat than L or V mice. Fasting glucose trended lower in L mice compared to NL mice, but there was no difference in insulin levels between groups. The area under the curve of glucose tolerance test was not different between groups. Pancreases from L mice had increased numbers of islets compared to NL and V mice. Insulin action was assessed in chow-fed, conscious, unrestrained L, NL, and V mice using the euglycemic-hyperinsulinemic clamp technique. Tail-vein glucose was clamped at 100-120 mg/dL. The normalized glucose infusion rate to insulin was significantly lower (p=0.01) in NL mice (41.9 +/- 17) compared to V mice (91.8 +/- 14 and L mice (83.8 +/- 27). Our results suggest that pregnancy and lactation significantly alter the metabolic functions of liver, adipose, muscle, and pancreas. Furthermore, a history of lactation improves insulin sensitivity in parous mice. Further study of the metabolic changes occurring during lactation may have wide-ranging implications for women’s health. Presentation: Thursday, June 15, 2023