During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a prometastatic niche. These data suggest a mechanism for increased liver metastasis in breast cancer patients with recent childbirth. It is unknown whether the human liver changes in size and function during pregnancy and weaning. In this study, abdominal imaging was obtained in healthy women at early and late pregnancy and postwean. During pregnancy time points, glucose production and utilization and circulating bile acids were measured. Independently of weight gain, most women’s livers increased in size with pregnancy, then returned to baseline postwean. Putative roles for bile acids in liver growth and regression were observed. Together, the data support the hypothesis that the human liver is regulated by reproductive state with growth during pregnancy and volume loss postwean. These findings have implications for sex-specific liver diseases and for breast cancer outcomes.

BACKGROUND: During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a pro-metastatic niche. These data suggest a mechanism for increased liver metastasis in postpartum breast cancer patients. OBJECTIVES: Investigate if the human liver changes in size and function during pregnancy and weaning. METHODS: Abdominal imaging was obtained in healthy women at early and late pregnancy, and post-wean. During pregnancy time points, endogenous glucose production was measured and fasting blood taken to measure bile acids. RESULTS: Independent of weight gain, most women's livers increased in size with pregnancy, returning to baseline post-wean. Putative roles for bile acids in liver growth were observed in pregnant women and rodents. CONCLUSIONS: The human liver is regulated by reproductive state with growth during pregnancy and volume loss post-wean. These findings may have broad implications for sexspecific liver diseases and cancer.

Background: In nonpregnant adults, increased ectopic lipid stores [intrahepatic (IHL), intramyocellular (IMCL)] are associated with increased risk of diabetes mellitus and nonalcoholic fatty liver disease. While the amount of weight gained during pregnancy is significantly associated with the amount of weight retained after delivery, it is unclear whether weight gain during pregnancy is correlated with increased IHL or IMCL stores; thus, predisposing women with postpartum weight retention to increased risk of diabetes and NAFLD. Methods: We evaluated 36 women with an enrollment BMI between 18.5 and 38 kg/m2 at a mean (min-max) of 15.6 weeks (12.9-17.3) gestation and again at 34.2 (32.1-37.7) weeks gestation. Women with pregestational diabetes and multifetal pregnancies were excluded. Participants underwent 1H magnetic resonance spectroscopy to assess IHL and IMCL content, and air displacement plethysmography to assess body weight, percent (%) body fat, fat mass, and lean mass. Results: The participants were primarily white (89%) with mean age of 30.4 years. Table shows mean, standard deviation (SD), and Pearson’s correlation coefficients for all measures. Conclusion: Gestational weight gain tracks closely with increase in fat mass during pregnancy, but is not significantly correlated with change in IHL or IMCL stores.able. Means, standard deviations, and Pearson’s correlation coefficients for weight and total and ectopic fat measures at early pregnancy and from early to late pregnancy.MeasureEarly pregnancy Mean (SD)Mean change (SD) from early to late pregnancyCorrelation of change with weight changeWeight (kg)72.2 (10.3)10.4 (3.2)--BMI (kg/m2)25.2 (3.4)3.6 (1.1)--Body fat (%)33.6 (6.5)-0.6 (3.0).38*Fat mass (kg)24.8 (7.6)3.1 (3.1).70*Lean mass (kg)47.5 (5.1)7.4 (2.4).40*IHL (% water peak)0.5 (0.2)0.1 (0.2)-.12IMCL (% water peak)0.9 (0.4)0.2 (0.5)-.25*p<.05 Disclosure K. Vesco: None. M.C. Leo: None. M. Francisco: None. E. Baetscher: None. W. Rooney: None. N.E. Marshall: None. J.Q. Purnell: Advisory Panel; Self; Novo Nordisk Inc..