As the saying goes, you can't get something for nothing, and nowhere is this clearer than in our own bodies. Everything that we do, from breathing to walking to even sleeping, requires energy, which we gain from the food that we eat. In this modern age where food, and thus energy, is available 24/7, surely all the millions of processes our bodies undertake should be limitless? Unfortunately, they are not: at a certain point we are all limited by our physiology – our metabolic rates can simply go no higher. But where, or what, is setting this limit? To answer this, scientists have turned to lactating mice, as this is the most energetically costly activity a mammal is likely to perform. It is thus also the most likely to drive the metabolic rate to its limit, explains John Speakman from the University of Aberdeen, UK, and the Chinese Academy of Sciences, Beijing.
Speakman recalls that ‘there was a suggestion back in the 1980s that the
Since proposing the heat dissipation hypothesis, Speakman and his team have turned their attention to tracking body temperature changes during pregnancy (p. 2328) and lactation as well as investigating variability amongst animals. Speakman explains that even without changing room temperature the maximum food intake (and thus milk production) can vary widely amongst mums. Although the average maximum intake is 23 g day−1, maximums can range anywhere between 13.2 and 27.6 g day−1. One theory from the 1950s suggested that these differences were pre-programmed during pregnancy by fetal litter size, so that mums with small litters would need to eat less and thus have lower maximum intake. However, this pre-programmed theory was incompatible with the observation that lactation could be adjusted – for example, when mothers were exposed to the cold. To investigate, the team either increased or decreased the size of the litters immediately after birth. They found that maximum food intake did not correlate with fetal litter size – in fact the mum with the smallest fetal litter size of six was the only mum to successfully foster the largest litter size of 16 (p. 2339). To see whether this maximum intake was genetic, the team set up a cross-fostering program where only half the pups were suckling milk from their birth mum. The team measured the pup's maximum food intake when the time came to rear their own offspring, and found that maximum rates were most similar to their birth mums regardless of whether they had been fed by their birth or foster mum, indicating that the variation was genetic (p. 2308).
However, while this work was ongoing, the debate over what was causing the limit carried on. Zhi-Jun Zhao from Liaocheng University, China, found that he couldn't reproduce Speakman's observations in Swiss Webster mice. When he shaved the mums they ate more but the pups didn't grow bigger. Could the peripheral limit theory be right after all? ‘We wanted to see if there were other things going on that we'd not thought about or get some resolution of why he got a different result to us. So the best way to do these things is to collaborate’, explains Speakman.
So Zhao came over to Aberdeen for a year, and rather than repeat the experiment, the pair along with colleagues from Speakman's lab decided to test the peripheral limit theory in MF1 mice in a new way. Rather than making thermoregulation the ‘extra’ process that required additional intake, they made exercise the extra activity (p. 2316). The team fed lactating MF1 mice just 80% of the daily maximum, but gave them option to run a set distance to access as much food as they wanted. If running was just an extra process, they could then simply eat enough to replenish the cost of running as well as gain the extra 20% needed to fuel lactation. However, the team found that none of the mums ate more after their run. In fact, mums made to run the furthest before accessing more food did so at the expense of their pups, and weaned the lightest litters. Zhao and Speakman both conclude that it again points towards the inability to dissipate enough of the heat generated through simultaneously running and producing milk.
However, this still didn't explain Zhao's observations in Swiss Webster mice.
Luckily, Speakman took up a position the Chinese Academy of Sciences in 2011 and was able to continue the collaboration and help determine why this strain of mice wasn't producing more milk (p. 2349). ‘Maybe Zhao's pups just couldn't convert extra milk into more growth’, says Speakman. ‘So the question is did they not produce the milk because they couldn't or because the pups couldn't use it?’ To test this, the team reduced litter sizes down to 1–9 pups – well below their average litter size of 12. This way they knew that the mums already definitely had the capacity to suckle 12 pups. They then placed half the mums and litters at 21°C and the others at 5°C. If pups were limited by the mammary glands' capacity only, mice from the smallest litters would grow the most. If heat dissipation played a role, pups with mums incubated at 5°C would grow more compared with their warmer compatriots. However, the team observed neither: the fewer pups a mum was given the less she ate. Pups reared at 21°C were almost all the same weight regardless of how big their litter was. So, for Swiss Webster mice, it seems that pup demand first and foremost affects how much the mum eats and her milk production.
‘I think the bottom line is that it seems that the limit story is much more complex than we imagined and in fact there isn't one solution. In some situations it's very likely to be heat dissipation, in other situations it's very likely to be growth limitation of the offspring, but one thing that we can definitely eliminate is that the limit to sustained energy intake is programmed in pregnancy’, concludes Speakman.