When you think of the ideal place to live, most of us yearn for the tropics. But it turns out there may be some extra benefits to living in a cold climate (and not just lower rent!). New research from an international collaboration led by the lab of Dr. Christian Wolfrum at ETH Zurich may have you packing your bags for the poles. In their latest, the talented team has uncovered an epigenetic link between chilly paternal temperatures (prior to conception) and the levels of brown adipose tissue in offspring.
Brown adipose tissue is sometimes called “good” fat, as it’s important for keeping us warm—primarily through the function of uncoupling protein 1 (UCP1). The inaugurate building block for this study was the apparent link between conception in colder months, increased active brown fat, and decreased BMI, as determined by retroactively analyzing PET scans of 8,440 individuals.
The team then turned to mouse models to better uncover the details of this phenomenon. Here’s what they found:
- Cold exposure of paternal mice (P-CE) prior to mating results in phenotypic changes in offspring
- P-CE progeny have more active brown fat as measured by basal UCP1 expression, and increased capacity for thermogenesis
- Offspring have an improved systemic metabolism—increased oxygen consumption, decreased basal glucose levels, and better insulin sensitivity
- Upon cold exposure, there is increased UCP1 expression and oxygen consumption when comparing P-CE offspring to matched controls
- These effects are mediated through activation of brown adipose tissue, and ablation of brown adipocytes in transgenic mouse lines leads to loss of the improved metabolic phenotype
- When P-CE offspring are fed a high fat diet, they consume more food but have lower body fat as compared to control mice
- P-CE offspring show improved insulin sensitivity and lower circulating triglyceride levels
- RNA-seq analysis of brown adipose tissue from P-CE and control offspring revealed unique transcriptional profiles
- In the P-CE offspring, they observed an upregulation of brown fat regulators like Adrb3 and an downregulation of muscle-specific genes
- Whole-genome bisulfite sequencing of sperm from cold-exposed and control mice uncovered several differentially methylated regions (DMRs); some of these DMRs reflect the observed transcriptional differences, and may mediate the intergenerational effect
The authors propose that cold exposure of males alters the sperm methylome, which in turn may induce cold-adaptive phenotypic changes in offspring. So should aspiring Dads-to-be grab the ice packs out of the freezer? Senior author, Christian Wolfrum shares that “it is likely that the exposure to cold needs to persist over a longer period for it to have an effect on epigenetic programming. Taking a plunge in cold water […] probably won’t be enough.” We hear Antarctica is nice though.