The Effects of High-Fat Diet Exposure In Utero on the Obesogenic and Diabetogenic Traits Through Epigenetic Changes in Adiponectin and Leptin Gene Expression for Multiple Generations in Female Mice

• Published in: Endocrinology (Philadelphia) Vol. 156; no. 7; pp. 2482 - 2491
• Main Authors: Masuyama, Hisashi, Mitsui, Takashi, Nobumoto, Etsuko, Hiramatsu, Yuji
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.07.2015
• Subjects: Adiponectin - genetics; Animals; Blood Glucose - metabolism; Body Weight; Diet, High-Fat; Epigenesis, Genetic - genetics; Female; Gene Expression; Glucose Intolerance - genetics; Glucose Tolerance Test; Hypertriglyceridemia - genetics; Insulin - metabolism; Insulin Resistance - genetics; Leptin - genetics; Metabolic Syndrome - genetics; Mice; Mice, Inbred ICR; Obesity - genetics; Pregnancy; Prenatal Exposure Delayed Effects - genetics; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Triglycerides - metabolism
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2014-2020

Recent studies demonstrate that epigenetic changes under malnutrition in utero might play important roles in transgenerational links with metabolic diseases. We have previously shown that exposure to a high-fat diet (HFD) in utero may cause a metabolic syndrome-like phenomenon through epigenetic modifications of Adiponectin and Leptin genes. Because an association of obesity between mother and offspring endured in multiple generations, we examined whether HFD exposure in utero might affect the metabolic status of female offspring through multigenerational epigenetic changes of Adiponectin and Leptin genes and whether a normal diet in utero for multiple generations might abolish such epigenetic changes after exposure to a HFD in utero using ICR mice. We observed that the effect of maternal HFD on offspring over multiple generations in metabolic syndrome-like phenomenon such as weight and fat mass gain, glucose intolerance, hypertriglyceridemia, abnormal adiponectin and leptin levels, and hypertension, were accumulated with expression and epigenetic changes in Adiponectin and Leptin genes. A normal diet in utero in the subsequent generations after HFD exposure in utero diminished, and a normal diet in utero for 3 generations completely abolished, the effect of HFD in utero on weight and fat mass gain, insulin resistance, serum triglyceride, adiponectin, and leptin levels, with epigenetic changes of Adiponectin and Leptin genes. Exposure to a HFD in utero might affect glucose and lipid metabolism of female offspring through epigenetic modifications to Adiponectin and Leptin genes for multiple generations. Obesogenic and diabetogenic traits were abolished after a maternal normal diet for 3 generations.