Maternal high-fat diet regulates glucose metabolism and pancreatic β cell phenotype in mouse offspring at weaning

PeerJ. 2020 Jun 22:8:e9407. doi: 10.7717/peerj.9407. eCollection 2020.

Abstract

Background: Maternal malnutrition is a critical factor in determining the risk of obesity and glucose intolerance in offspring. However, little is known about the effects of a maternal high-fat diet (HFD) on the β cell phenotype in offspring, which is a major factor in glucose homeostasis, especially during the early life of offspring.

Methods: Dams were randomly fed a HFD (60% kcal from fat) or a chow diet before pregnancy and during gestation and lactation. Glucose metabolism and the β cell phenotype were assessed in male offspring at weaning.

Results: Dams fed a HFD showed impaired glucose tolerance. A HFD predisposed the offspring to increased impairment of metabolic health, including obesity, glucose intolerance and insulin resistance, compared with offspring from chow diet-fed dams. Furthermore, increased islet sizes and islet densities were observed in male offspring from HFD-fed dams at weaning. There were increases in the insulin-positive area, β cell mass and β cell proliferation in male offspring from HFD-fed dams at weaning age. Next, we further determined whether a maternal HFD could affect β cell apoptosis in mouse offspring and found that there was no significant change in β cell apoptosis between the HFD and control groups.

Conclusion: Our study is novel in showing that a maternal HFD predisposes offspring to impaired glucose metabolism and has a profound effect on β cell mass and proliferation in offspring mice, which is observed in mice as early as at weaning age. However, further study to clarify the underlying mechanisms is warranted.

Keywords: Glucose metabolism; Maternal high-fat diet; Offspring; Weaning; β cell.

Grants and funding

This study was sponsored by the National Natural Science Foundation of China (No. 81800703), Beijing Municipal Natural Science Foundation (No. 7184252), the Fund for Fostering Young Scholars of Peking University Health Science Center (No. BMU2017PY008), China Diabetes Young Scientific Talent Research Project and Bethune-Merck Diabetes Research Fund of Bethune Charitable Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.