AsianScientist (May 2, 2018) – A research group in Japan has revealed the epigenetic changes required for cold temperatures to turn white fat into healthier beige fat. They published their findings in Nature Communications.
Gene expression is regulated by epigenetics, patterns of chemical signals that are not encoded in 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 marks throughout one’s lifetime, continually altering how genes are expressed.
When organisms are cold for a long time, the sympathetic nervous system responds by releasing adrenaline. If cold temperatures persist, those adrenaline signals eventually reach white fat cells. These white fat cells eventually transform into brown fat cells which can use lipids (fat) to generate heat to keep the body warm in a process known as thermogenesis. Brown fat is regarded as healthier and is not associated with the metabolic diseases linked to excess white fat.
In the present study, researchers led by Professor Juro Sakai from the University of Tokyo tracked how the epigenome changes after long-term exposure to cold temperatures. They revealed that epigenetic changes cause energy-storing white fat cells to become heat-producing brown-like, or beige fat cells.
“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 Sakai.
The first step of the environmental epigenetic control pathway involves the cell initiating a specific change to one amino acid in a protein named JMJD1A, which then recruits other proteins. In step two, this JMJD1A protein complex is recruited to genes that initiate thermogenesis, changing their epigenetic pattern so that they become active. Those epigenetic changes transform white fat cells into beige 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, the researchers said.
“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.
Current drugs for metabolic diseases rely on hormones that are systemic throughout the entire body, or drugs that target entire proteins. Sakai’s research team imagines a future where metabolic diseases can be treated by targeting single amino acids.
The article can be found at: Abe et al. (2018) Histone Demethylase JMJD1A Coordinates Acute and Chronic Adaptation to Cold Stress via Thermogenic Phospho-switch.
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Source: University of Tokyo; Photo: Shutterstock.
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