Temperature Influences Fat Epigenetics: Study
Cold stress is a major threat for warm-blooded animals, and therefore adaptive thermogenesis to combat cold stress is crucial for survival. Now, a new study has found a molecular mechanism that controls how lifestyle choices and the external environment affect gene expression.
The study by scientists at the University of Tokyo and Tohoku University in Japan demomstrates how epigenome changes after long-term exposure to cold temperatures, and how those changes cause energy-storing white fat cells to become heat-producing brown-like, or “beige,” fat cells.
Gene expression is regulated by epigenetics – patterns of chemical signals that are “above” the gene sequence. An individual’s gene sequence is determined at conception, but the external environment and an individual’s lifestyle can change the epigenetic sequence throughout a lifetime, continually altering how genes are expressed.
“We believe that this is the first time that anyone has collected data to prove that there are two steps between the environmental stimuli and epigenetic changes,” said Professor Juro Sakai from the University of Tokyo and Tohoku University, an expert in the epigenetics of metabolism.
We have three types of fat- brown, white and, now we are finding out, beige. Brown fat, which is the
fat we are born with that allows babies at birth to go from a warm uterus of 98 degrees Fahrenheit to room temperature of around 74 degrees. This fat is not associated with health problems. It got its name because it looks brown under a microscope due to its containing many mitochondria, the powerhouses of cells that produce energy. Mitochondria contain a protein called UCP1 that breaks down fat to make heat.Researchers in the study of mice at the University of Tokyo found that long-term cold exposure can actually stress the white fat cells into developing more mitochondria and eventually becoming more efficient, calorie-burning beige cells.
One group of mice was kept at 39 degrees Fahrenheit and another at 86 degrees Fahrenheit for one week. Without any change in diet, the mice that were kept at the lower temperature had more thermogenic activity- meaning their cells were able to burn calories and stored fat to create heat.
The researchers explain that the process begins when the cold kick-starts a change in a protein called JMJD1A. When combined with other proteins, this altered protein changes the way a gene functions in producing heat. Subsequently, a chemical process called thermogensis is initiated which changes epigenetic patterns so white fat cells are transformed into beige fat cells, which function like brown fat cells.
The JMJD1A protein is involved in a wide variety of other processes, including cancer, infertility, stem cell renewal, and sex determination of an embryo. However, Sakai’s research team has discovered sites within the protein sequence that are extremely specific for controlling different activities of the protein. Manipulating those specific amino acids may provide precision drug targets.
“Understanding how the environment influences metabolism is scientifically, pharmacologically, and medically interesting. Our next experiments will look more closely at epigenetic modifications within the thermogenesis signaling pathway so that we may manipulate it,” said Sakai.
