We recently published work on the responses of mice to differences in dietary macronutrients in Cell metabolismArticle Dietary Fat, but Not Protein or Carbohydrate, Regulates Ener...
After it was published it got a lot of social media attention mostly from non-scientists and mostly along the lines of well OK but its just mice so we can ignore it. My initial reaction was that surely the mouse is a good model of humans. But then I got to thinking well maybe it isn't and the people dismissing the study have a point.
So my question is what are the most significant differences between mice and humans in terms of their adipose tissue metabolism, general control of food intake, and energy balance, that would invalidate (or at least make us question) their use as a model of human energy balance?
Are there examples where mice clearly respond differently to humans to dietary manipulations, or in their metabolic responses to food intake?
thanks for bringing this to my attention. much appreciated.
cheers
John
This seems at least peripherally relevant: differences in how humans and mice maintain insulin sensitivity under isocaloric high-fat feeding:
https://www.cell.com/cell-metabolism/fulltext/S1550-4131%2818%2930565-5
Thanks Michael and Entedhar for the inputs, especially the frontiers paper by Tim and Daniella, both of whom I know well, but I somehow missed this paper from them. Apologies for the delay in response but I was away on vacation and then at a conference so just now picking up on messages and emails etc.
Hi John,
Great question! Just a few thoughts off the top of my head...
1) humans are born with a substantially higher fat-cell to muscle-cell ratio (i.e., humans are the 'fattest' of all terrestrial and many marine mammals). This means that, ceteris paribus, more nutrient-energy will be partitioned to storage in adipocytes during each post-prandial period. Thus, the focus on energy expenditure will always be misleading...the focus should be on nutrient-partitioning...or as I wrote, 'it is not what you eat, but what your body does with what was eaten' (i.e., nutrient-energy metabolism and partitioning).
For details, please see: Archer E, Pavela G, McDonald S, Lavie CJ, Hill JO. Cell-Specific “Competition for Calories” Drives Asymmetric Nutrient-Energy Partitioning, Obesity, and Metabolic Diseases in Human and Non-human Animals. Frontiers in Physiology. 2018;9(1053).
2) mice are small creatures w/ a high strength-to-weight ratio. Thus, in their natural environs rodents' physical activity (PA) is an order of magnitude greater than humans; yet it is a trivial component of their TDEE compared to basal and adaptive metabolism. This latter point is due to greater surface area-to-mass ratio and heat loss. In humans, PA is 25-30% of TDEE. Thus, PA is major determinant of nutrient-energy partitioning in humans but not in small mammals (e.g., rodents) because a greater amount is partitioning to the maintenance of body temp.
3) because of point 2 above, PA will have a greater impact on energy intake in humans than in smaller mammals even in thermo-neutral environments.
4) laboratory rodents have been bred to survive captivity for 400+ generations (w/ no predators, few pathogens, ad libitum food, etc., etc.) and most of this breeding was in extremely sedentary conditions. Humans have been sedentary for only 3-4 generations. Try 'feral' mice housed in more 'natural settings' and see if your results hold...
More to follow...
Cheers,
Ed
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