Cold temperatures during winter are not only uncomfortable for us – depending on how we dress – but also challenging for animals. Whereas large mammals usually just grow thicker hair during winter for protection from the cold, many small mammals, as well as the newborns of larger species, typically use a more complex mechanism to stay warm in winter: they produce heat in a specialized organ, the brown adipose tissue (also often called brown fat), in a process involving the thermogenic protein UCP1. But this mechanism has been lost in some species. Pigs, for example, lost this mechanism about 20 million years ago. As a result, many pig species are very sensitive to cold and early death of piglets is a major problem in the swine industry. But not all pig breeds are sensitive to cold, suggesting that other mechanisms of heat production must have evolved in those breeds.
Jun Lin from the Chinese Academy of Science and colleagues from different institutes speculated that another protein called UCP3, basically a relative of UCP1, could play a role in heat production in pigs. The team focused on the Tibetan pig, a breed that occurs at high altitudes and is quite tolerant to cold exposure. The researchers first confirmed that Tibetan pigs do not have brown adipose tissue or functional UCP1. They then placed the piglets in a cold room and compared the response of the cold-tolerant Tibetan pigs with the response of Bama pigs, a species that is known to be very sensitive to cold exposure. In addition to looking out for a drop in body temperature in both breeds, the researchers also compared the structure of fat cells at body locations in which brown fat occurs in other species, as well as expression patterns of the genes that are active after cold exposure.
The study found that both breeds shivered when exposed to the cold and were able to maintain a normal body temperature thanks to the muscle contractions. However, treating the animals with a drug that inhibits shivering led to a marked decrease of body temperature in the Bama pigs, whereas the Tibetan pigs were still able to keep warm. This indicated that Tibetan pigs must have an alternative heat production mechanism. Furthermore, when the team compared the structure of fat cells from the two breeds after they had been kept in the cold room for a few hours, they found evidence of the appearance of beige fat cells, which have similar heat production potential to that of brown adipose tissue, in Tibetan pigs but not in Bama pigs.
Looking into the genes that were upregulated in both breeds after cold exposure, the team again found marked differences. While the genes that were upregulated in the cold-sensitive Bama pigs had nothing to do with heat production, the genes that showed increased expression in Tibetan pigs did. And one of them was the gene coding for the UCP3 protein, which occurred primarily in the beige fat cells. Further analyses then revealed similarities in the protein structure between pig UCP3 and UCP1 in rodents, the protein that is involved in heat production in brown adipose tissue. Importantly, when Lin and colleagues extended the analysis to other breeds, they found the same results in Min pigs – another breed that can tolerate cold temperatures – but not in breeds that have trouble coping in the cold.
Although it is not yet clear how UCP3 works, this study suggests that it is involved in heat generation and contributes to the cold tolerance of pig species living in cold habitats.