Abstract
Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to high-fat (HFD) and normal diet (ND) fed mothers were studied at week 1 and months 1, 6, 12 of life. Liver and thymus glucose uptake (GU) was measured with positron emission tomography during hyperinsulinemic-isoglycemia. Histological analyses were performed to quantify liver steatosis, inflammation, and hepatic hematopoietic niches (HHN), and thymocyte size and density in a subset. The protocol was repeated after maternal-diet-normalization in the HFD group. At one week, HFDoff were characterized by hyperglycemia, hyperinsulinemia, severe insulin resistance (IR), and high liver and thymus GU, associating with thymocyte size and density, with elevated weight-gain, liver IR, and steatosis in the first 6 months of life. Maternal diet normalization reversed thymus and liver hypermetabolism, and increased HHN at one week. It also normalized systemic insulin-sensitivity and liver fat content at all ages. Instead, weight-gain excess, hyperglycemia, and hepatic IR were still observed at 1 month, i.e., end-lactation. We conclude that intra-uterine HFD exposure leads to time-changing metabolic and immune-correlated abnormalities. Maternal diet-normalization reversed most of the effects in the offspring.
Highlights
Obesity, commonly due to the intake of high-fat, energy-rich foods, is a common cause of chronic diseases and metabolic dysregulation [1]
This study is part of a large project focused on cardiometabolic consequences of maternal obesity [2,3,28] and here we report our advancement of knowledge concerning the liver and thymus
Our data document that maternal obesity leads to time-changing liver and thymus metabolic dysfunction in minipigs
Summary
Commonly due to the intake of high-fat, energy-rich foods, is a common cause of chronic diseases and metabolic dysregulation [1]. Its impact has increased worldwide, involving a large number of women of childbearing age, with negative health consequences for mothers and offspring [2,3]. The intrauterine metabolic environment can permanently program the development and physiology of the offspring with short- and long-term health implications [4,5]. We previously reported that high-fat diet (HFD) consumption during pregnancy affects the brain glucose metabolism and myocardial function in the offspring [2,3], but the metabolic impact on liver and immune organs, from birth to late adulthood, has not been elucidated.
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