The researchers revealed two metabolic pathways that may play a role in the DOHaD hypothesis

The hypothesis on the origins of the development of health and diseases (DOHaD) is corroborated by numerous human and animal epidemiological studies. He states that the early nutritional environment makes people vulnerable to lifestyle-related diseases, such as obesity, diabetes, and heart attacks, in adulthood. Many of these diseases have reduced mitochondrial metabolism in body tissues. Researchers from the University of Kumamoto in Japan have revealed that two metabolic pathways involved in energy metabolism could play a role in the DOHaD hypothesis.

All cells regulate gene expression related to metabolic pathways and adapt to environmental changes such as nutrition fluctuations, oxygen supply, exercise and temperature. The cells of the human body use two types of cellular metabolism: mitochondrial respiration and glycolysis. Mitochondrial respiration produces energy for the cell when oxygen is supplied (aerobic) and glycolysis is used when oxygen is scarce (anaerobic). The activity of metabolic genes changes significantly as the method of energy production moves between these two mechanisms. Some of the most critical changes are due to acetylation of histones and methylation (the addition / removal of acetyl and methyl groups) of lysine amino acids. SIRT1 deacetylase enzymes and LSD1 demethylase are particularly important in the regulation of metabolic genes since they remove the acetyl and methyl groups, respectively, from the target proteins.

Two metabolic pathways, NAD⁺ -SIRT1 and FAD-LSD1, regulate the function of specific genes and transmit nutrient signals. Researchers at Kumamoto University have recently revealed that these two pathways are controlled by dietary vitamins and nutritional hormones, induce metabolic activity, and develop specific tissue properties in fat cells and skeletal muscles. They found that the FAD-LSD1 pathway suppresses mitochondrial metabolism and induces fat accumulation under conditions of obesity.

According to the DOHaD, people affected by early malnutrition may have low birth weight and increased risk of lifestyle-related diseases in adulthood. Although the mechanisms behind this situation have not been clarified, researchers believe that at least two responses work at different times. the immediate response consumes stored energy and gives priority to maintaining life adaptive response "programs" the body so that it stores energy in anticipation of future famine crises. This is considered a natural survival strategy for nascent malnutrition. An adaptive response can easily adapt to undernutrition, but it makes a person more susceptible to lifestyle-related diseases, such as obesity and diabetes, in the event of excessive overeating.

NAD⁺-The SIRT1 path burns energy and the FAD-LSD1 pathway stores energy and together they can remodel metabolic tissues. In muscle development, the SIRT and LSD1 pathways selectively promote slow and rapid formation of seizure fibers, which increases susceptibility to lifestyle-related diseases. Thus, researchers believe that these enzymes are involved in DOHaD mechanisms. Specifically, this SIRT1 may play a role in immediate response and LSD1 may be involved in the adaptive response.

Speaking about future activities, Professor Mitsuyoshi Nakao, Director of Research, said: "We hope that our work will contribute to the development of new disease prevention and control strategies by improving the understanding of lifestyle-related diseases and nutrition of young parents and babies during perinatal periods. "

This job was posted online in "Trends in endocrinology and metabolism"May 5, 2019.