New Experimental Study on Pigs Confirms that Non-shivering Thermogenesis Reduces Adiposity

Pigs are deficient in UCP-1, which mediates non-shivering thermogenesis; scientists successfully inserted the UCP-1 gene into pig embryos; these pigs exhibited improved thermoregulation, elevated lipolysis and lower adiposity

Noah Carl
Noah Carl
Oct 24, 2017 · 3 min read

Last week, I posted about temperature control and adaptive thermogenesis in humans. My conclusions were that cold exposure can help to prevent weight gain, and that central heating may have contributed to the rise in obesity.

Yesterday, a fascinating new paper by Zheng et al. (2017) was published in the journal PNAS, which provides evidence that non-shivering thermogenesis reduces adiposity in transgenic pigs.

The authors begin by noting that the protein UCP-1 (which mediates the process of non-shivering thermogenesis) is present in most placental mammals, but has been lost in the pig lineage. The gene apparently became non-functional in pigs around ~20 MYA, when they lived in environments warm enough that adaptive thermogenesis did not confer a survival advantage. As a consequence, the wild pig is apparently the only ungulate that builds a thermoprotective nest before giving birth. In addition, pigs have unusually high levels of adiposity.

Using a new method called CRISPR/Cas9-mediated site-specific integration, the authors successfully inserted a functional version of the UCP-1 gene into embryonic pig cells. Once these so-called “knock-in” piglets had been born, the authors carried out a number of tests comparing them to normal, wild-type piglets.

First, they utilised FDG-based positron-emission tomography (the method that I mentioned in my previous post), and detected brown fat that became metabolically active under cold exposure in the knock-in piglets, but did not detect brown fat in the wild-type piglets. Their Figure 2A is shown below (KI denotes knock-in; WT denotes wild-type):

Second, they measured the piglets’ body temperatures over 4 hours of cold exposure, and found that the knock-in piglets exhibited markedly better thermoregulation. In the knock-in group, body temperature fell to 38.4°C during the first hour, but then remained above 38°C for the remaining three hours. By contrast, in the wild-type group body temperature fell to nearly 36°C during the first two hours, and then recovered to only around 37.5°C by the end of the four hours.

Third, they measured the piglets’ body-weight, carcass fat percentage, and backfat thickness. Interestingly, no significant differences in body-weight were observed between the two groups. However, the knock-in piglets had 24% lower carcass fat percentage, and 26% thinner backfat. These results imply that, while UCP-1 activity did not reduce overall body-weight, it did improve the ratio of fat mass to lean mass.

Fourth, they measured expression levels of two enzymes involved in lipolysis (the breakdown of fats)––phosphohormone-sensitive lipase and adipose triglyceride lipase––in the piglets’ cells, and documented significantly higher levels in the knock-in group.

Fifth, they monitored piglets’ physical activity using a logger that recorded movements in three dimensions on a minute-by-minute basis. No significant difference was observed in physical activity between the two groups, indicating that the knock-in piglets did not compensate for non-shivering thermogenesis by doing less physical activity.

In conclusion, transgenic pigs carrying the UCP-1 gene exhibit improved thermoregulation, elevated lipolysis and lower adiposity. This provides indirect evidence that cold exposure could be an effective strategy for preventing fat gain in humans.

Noah Carl

Noah Carl

Independent researcher

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