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How maternal obesity epigenetically reprograms liver metabolism in offspring, predisposing them to metabolic disease.

Episode Summary: Dr. Elvira Mass talks about macrophages, specialized immune cells that vary by tissue and play crucial roles beyond fighting infections, such as supporting organ function; Kupffer cells (liver macrophages) and how maternal obesity during pregnancy reprograms these cells in offspring, leading to fatty liver disease, fibrosis, and even cancer later in life, based on mouse studies showing epigenetic and metabolic shifts like increased glycolysis, with insights into developmental windows, nutritional mismatches, and broader implications for human health.

About the guest: Elvira Mass, PhD, is a Professor of Developmental Immunology at the University of Bonn in Germany, where her lab focuses on the development and function of macrophages in various tissues.

Discussion Points:

• Macrophages are diverse, tissue-specific cells that develop from embryonic precursors, performing unique tasks like providing growth factors in organs.
• Kupffer cells in the liver monitor blood from the gut and are exposed to maternal nutrients during fetal development.
• Maternal obesity (induced in mice via high-fat diets) programs offspring Kupffer cells epigenetically, leading to fatty liver in newborns and progression to diseases like cancer, even on normal diets.
• A "nutritional mismatch" between in utero high-fat exposure and postnatal normal diets worsens liver issues, as cells are "prepared" for excess high-fat intake but face scarcity.
• Key mechanism: Reprogrammed Kupffer cells overproduce apolipoproteins, driving excess lipid uptake in liver cells (hepatocytes), linked to transcription factor HIF-1α and a shift to inefficient glycolysis.
• Offspring from obese mothers show sex differences (males affected earlier) and persistent changes.
• Human parallels: Rising childhood fatty liver (once rare and tied to alcoholism) correlates with maternal obesity; studies like Dutch Hunger Winter show early gestational disruptions cause lifelong issues.
• Broader factors: Microbiome changes, specific fatty acids, and environmental toxins like microplastics may also reprogram macrophages; diets in studies vary beyond fat content, affecting results.
• Advice: Maintain consistent healthy habits pre- and during pregnancy; avoid sudden diet shifts, as developmental windows are critical for long-lived cells like Kupffer cells.

Reference Paper:

• Study: Kupffer cell programming by

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