The Siberian hamster ( Phodopus sungorus ) is a model organism for studying seasonal biological rhythms. They feed during the spring and early summer, but as fall approaches and the length of the day decreases, their bodies undergo great changes.
Hamsters lose almost all of their body weight, most of it through fat, and limit their food intake to 30-40%. They do not hibernate but have a modest reduction in their body temperature during the day to conserve energy. Their fur thickens and changes color to a more intense white. During this period, hamsters become infertile until they begin to prepare for the next breeding season.
How does the Siberian hamster detect that it must prepare for winter?
Analysis of the first complete sequenced genome of the Siberian hamster shows how it adapts its body and energy use to survive the winter. The study has been published in the journal Proceedings of the National Academy of Sciences .
This study has included the analysis of the transcriptome of gene expression in the brain in both summer and winter, which reveals a cascade of signals that prepare the rodent for winter, and that is triggered by the length of the day.
This new study shows that changing the length of the day was enough to trigger these changes regardless of the temperature or how much food is available.
“We hope it will be a tool to discover and do more research on this interesting biological puzzle, which is how organisms use the energy of nature over the course of a year,” said Brian Prendergast PhD, professor of psychology at the University of Chicago and one of the study authors.
The research is a collaborative project between senior author Tyler Stevenson, Ph.D., a former postdoctoral collaborator in Prendergast’s lab, now at the Glasgow faculty. Stevenson worked with Riyue Bao, Ph.D. from the University of Chicago Bioinformatics Research Group to assemble and analyze the mouse genome and transcriptome in order to understand the activity of genes in the brain in both summer and winter conditions.
[box type = »shadow» align = »» class = »» width = »»] The transcriptome is the set of all RNA molecules (also called transcripts) present in a cell or group of cells at a given time. [/ box]
The thyroid and hypothalamus keys
The researchers focused on the activity of the hypothalamus , the part of the brain that initiates a large number of very important metabolic processes such as releasing hormones, sending signals to the thyroid, and controlling body temperature, sleep, and hunger.
Modern science has a good understanding of the processes that maintain weight in the short term through appetite, food intake and energy expenditure. However, this new study sought to see how animals such as the Siberian hamster maintained body weight on an annual cycle.
Stevenson and Bao worked together to interpret data on how genes were expressed, looking for differences between samples taken from hamsters during the summer and winter periods. Once Bao spotted those differences and identified which biological processes might be affected, he turned to Stevenson for validation.
“Our collaboration is quite dynamic, like a two-way street,” Bao said. «I would pass him the data and ask him if a certain route made sense. Then he could recognize a certain RNA molecule or candidate gene and ask for more information.
They targeted a gene called pomc . For years, scientists have speculated that it is involved in the long-term regulation of weight and energy balance in many animals, but “it was the steps that controlled pomc expression that had been a mystery,” Stevenson said. “The studies we designed served to fill in the gaps and it was simply a matter of connecting the dots.”
That chain of events begins with the thyroid hormone, called T4. The T4 hormone is readily available in the bloodstream, and when the amount of daylight begins to increase in the spring, the hamster produces enzymes called deiodinases. These enzymes remove an iodine molecule from T4 and turn it into a more powerful hormone called T3 that controls the activity of the pomc.
During the summer, the increased production of T3 allows the hamsters to become fertile, and also increases the activity of the pomc, causing them to gain weight. As the days get shorter in the fall, T3 production declines, halting reproduction for the coming winter. The reduced T3 also downregulates (or turns off) the pomc, resulting in dramatic weight loss.
Stevenson also compared the Siberian hamster genome with other small mammals, such as mice and voles. He noted many differences between the animals in the sequence patterns, or motifs, in the promoter region of the pomc gene.
This section of DNA at the beginning of the gene sequence plays an important role in how it is transcribed into RNA and ultimately how the gene works. The Siberian hamster shares the same compound with other species that breed in season, suggesting that the way pomcs express themselves is key to managing summer-winter adaptations.
‘All animals show a seasonal level of biology, including humans. What our findings show, in hamsters, is that thyroid hormones acting in the brain where pomc is expressed provide long-term regulation of energy balance, ”Stevenson said.
“What is completely fascinating is that this process evolved in some animals, like hamsters and voles, and not in others, like sheep or humans . This tells us that there is great genetic variability between animals and indicates strong species-specific control of long-term energy balance, ”he said.
The Siberian hamster can give many clues about obesity
In a separate set of experiments, the researchers also restricted the amount of food for the hamsters . While this caused some changes in brain chemistry, it did not have an effect on pomce expression. Only long-term changes in day length had an effect on pomc.
Prendergast says that patterns like this make the Siberian hamster interesting not just for the way it handles seasonal adaptations, but for overall body weight as well.
“Researchers studying obesity should pay attention to this model because this is an animal that becomes obese reversible. Then you can lose almost half your body weight when the day says it’s time to lose weight, ”he said. “They are a wonderful puzzle to understand all these processes.”