You may have recently seen the headline:
This, like many other news headlines that idolize or demonize single foods and nutrients, probably made you second guess your own eating habits.
If you’d like to know what the study referenced by this headline actually showed, and why this headline is preposterous, read on 🙂
This headline was based on the following study:
Hu et al., Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice, Cell Metabolism (2018), https://doi.org/10.1016/j.cmet.2018.06.010
Scientists in this study performed three separate experiments.
Scientists fed mice twelve different diets:
- Six diets with 60% fat content by energy and protein content ranging from 5% – 30% by energy.
- Six diets with 20% fat content by energy and protein content ranging from 5% – 30% by energy.
Total carbohydrate content varied inversely with protein, but sucrose (sugar) and cellulose (fiber) levels were held constant.
Scientists again fed mice twelve different diets:
- Six diets with 10% protein content by energy and fat content ranging from 10% – 80% by energy.
- Six diets with 25% protein content by energy and fat content ranging from 8.3% – 66.6% by energy.
Total carbohydrate content varied inversely with fat, but sucrose (sugar) and cellulose (fiber) levels were held constant.
Scientists fed mice six diets.
Protein and fat content were held constant at 25% and 41.7% by energy, respectively, while varying sucrose content varied from 5%-30% by energy (totally carbohydrate constant at 33.3%).
Throughout all three experiments, the researchers assessed gene expression in the mice’s brains to see what effects food makeup had on hunger signaling pathways.
There were five strains of mice used in the study.
One strain – C57BL/6 – was exposed to all diets in all experiments, whereas the other four strains were only exposed to select diets to confirm findings from the C57BL/6 strains.
This article includes only pictures for the C57BL/6 strain, as the other strains corroborated the C57BL/6 results and including those figures would unnecessarily clutter this post more than it’s already been.
Protein content and energy intake
“At both levels of fat in the diet, total energy intake over the final week of measurement did not differ significantly in relation to protein content from 10% to 30%, with only a significant difference between 5% protein group and other protein groups (p = 1.40 x 10^-6 for 60% fat and p = 2.52 x 10^-5 for 20% fat) (Figures 2A and 2B).”
There does appear to be an inverse relationship between dietary protein content and energy intake, suggesting that increased protein intake decreases energy intake.
The researchers point out, however, that while there is a significant difference in energy intake between the 5% protein diet and the rest of the diets, variation in energy intake amongst diets from 10% – 30% protein content is not as significant.
I’m no statistician, but I’m not sure I see why they make that distinction.
The data is what the data is, and a trend line is a trend line.
To treat the 5% data point as somehow separate from the rest of the data doesn’t make sense to me, unless the researchers have some reason to believe that data point to be erroneous.
Protein content and body weight
Interestingly, while the researchers concluded that increased protein intake had no effect at all on totally energy intake (I’m still not sure I agree with this conclusion), they reported that increased protein content in the diet was associated with increased body weight.
“On the 60% fat diets with variable protein contents, body weight, lean mass, and adiposity all increased with increasing protein content in the diets at the end of the experimental period (p = 1.92 x 10^-5 for body weight, p = 2.30 x 10^-4 for fat mass, and p = 2.10 x 10^-4 for lean mass) (Figure 2C)…”
“On the 20% fat diets, body weight, body adiposity, and lean mass also increased as protein content increased from 5% to 20% protein, and then decreased when protein increased from 20% to 30% (p = 0.024 for body weight, p = 0.005 for fat mass, and p = 0.002 for lean mass) (Figure 2D).”
As protein content increased from 5% to 20%, body weight and body fat also increased, until decreasing again as protein content increased from 20% to 30%.
“Increased fat intake was related to higher energy intake of the mice fed on diets with either 10% protein (p = 3.24 x 10^-12) or 25% protein (p = 6.26 x 10^-12), even though the mice reduced their food intake when the fat content was increased in the diet (p = 8.71 x 10^-17 for 10% protein and p = 5.36 x 10^-8 for 25% protein) (Figures 4A and 4B).“
“Consequently, the increased energy intake caused the increase in body weight (p = 3.45 x 10^-7 for 10% protein and p = 1.68 x 10^-28 for 25% protein) and body fat mass (p = 1.51 x 10^-9 for 10% protein and p = 3.02 x 10^-24 for 25% protein), when dietary fat content was lower than 60% (Figures 4C and 4D).”
“Body weight and fat mass of the mice were slightly decreased because of significantly reduced food intake, when fat content in the diet was higher than 60% (Figures 4C and 4D)…”
“Therefore, increasing dietary fat content up to 60% fat leads to increased energy intake and causes adiposity in mice; however, further increase in the fat content led to a slight decrease in the energy intake via reduction in the absolute weight of food intake, and as a consequence, body weight and fat mass decreased.”
Let’s break all of that down.
As fat content of the feed increased, the mice ate less food.
While the mice were eating less food, they were still ingesting more calories due to the increased fat content and energy density.
Along with the increased energy intake came increased body weight and adiposity.
Energy intake and weight gain increased along with fat content up to 60%, at which point the mice ate sufficiently less such that their total energy intake and weight gain reversed.
So, here’s the question, dear reader.
Was it the fact that these mice were eating fat specifically that made them gain weight, or was it the fact that these mice were eating more total calories?
After all, body weight and adiposity track more closely with total energy intake than they do with fat content.
The researchers even state, “…increasing dietary fat content up to 60% fat leads to increased energy intake and causes adiposity in mice…” and “…the increased energy intake caused the increase in body weight…”
Sucrose content, energy intake, and weight gain
This isn’t part of the study isn’t terribly relevant to the purpose of this article, but I figured I’d include it since it was a part of the study.
“Energy intake over the last 10 days, however, remained constant in the mice fed on diets with variable sucrose content, with no significant differences between different sucrose groups (p = 0.320). Energy intake over the entire experimental period also showed the same trend (Figure S5B). Body weight (p = 0.855), fat mass (p = 0.620), and lean mass (p = 0.902) also did not differ significantly in relation to the sucrose content (Figure S5C).”
When the protein, fat, and carbohydrate intake of the food was held constant and the sucrose levels were adjusted, there was no change in energy intake or body composition.
I couldn’t locate any graphs for this data, so I suppose we’ll just have to picture it in our heads.
Hunger Signaling Pathways
Okay, so, this next part gets a little nerdy, so I’ll provided both the text from the study as well as a simplified explanation.
“Significantly positive associations were evident between the fat levels of the diet and the main hedonic signaling systems linked to food intake, i.e., dopamine (Drd1 and Drd5) and opioid receptor (Oprk1, Oprd1, and Oprm1) systems”
However, surprisingly there were strong significant negative associations between fat content and the two primary hypothalamic genes that drive hunger (Npy and Agrp; Figure 7). This was not paralleled by associations between dietary fat content and the primary hunger-suppressing genes (Pomc and Cartpt) (Figure 7; Table S2).
Nevertheless positive associations between fat content and elements of the serotonin (5-HT) receptor (Htr2a, Htr2c, Htr1a, Htr1b, Htr5a, and Htr4) signaling, upregulation of which is also generally considered inhibitory of intake, were significant.
These changes were consistent with the system attempting to compensate the enhanced hedonic signals and were mirrored by the reduced weight of food ingested as the fat content increased.”
So, there was a bit of a complex dance between appetite signals going on throughout all of this.
As fat content of the food increased, the hedonic (pleasurable/reward) signaling pathways were stimulated, but so, too, were inhibitory countermeasures to decrease food intake.
As we can see from the results of the study, these inhibitory countermeasures didn’t seem to sufficiently account for the changing energy density of the food until fat content exceeded 60% of energy.
Is fat consumption the only cause of weight gain?
Did we learn that “fat consumption is the only cause of weight gain”?
Did we learn that, “Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice”?
If we are to say that fat alone is the cause of weight gain, we would need to hold calories constant and compare what happened to body weight at different ratios of carbohydrate, protein, and fat.
When the mice did gain weight along with increased fat content, they were also consuming more calories.
Furthermore, the mice also gained weight when dietary fat was held constant and protein was increased.
As a matter of fact, both fat content and protein content were associated with weight gain and adiposity in a “U-curve” fashion – peaking at 20% for protein content and 60% for fat content.
So, why don’t the news headlines say anything about protein content driving weight gain?
Keep in mind also that, with protein content held steady, any change to fat content comes along with a change in carbohydrate content.
Why not point the finger at carbohydrate content, or study how it might play a role in all of this?
Even if we are to assume “cause” is intended to mean that fat content drives overconsumption, the conclusion that fat causes weight gain still isn’t accurate.
While hedonic pathways were stimulated along with increased fat intake, so were inhibitory signaling pathways.
On a related note, the mice ate less food mass as fat content increased.
While this decreased food intake didn’t completely account for the increased energy density until fat content exceeded 60%, it does demonstrate that fat content does not drive over-consumption.
Now, had the scientists titled the study, “Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake”, without the whole part about causing adiposity, then I’d understand.
After all, it appeared that the mice did attempt to compensate for the increased fat content by eating less total food.
However, the idea that fat content “causes adiposity” just isn’t supported by this study.
A better way to describe the study results
Here’s a better way to word what was observed in this study, even if it doesn’t make for good click-bait.
As the fat content of mouse feed increases, mechanisms that drive food intake as well as mechanisms that suppress food intake are stimulated, such that the net effect is a decreased intake of food mass.
Up to 60% fat content by energy, the drive to eat less food mass is not sufficient to account for the increased energy density, so mice ingest more total calories and gain weight.
Above 60% fat content by energy, mice sufficiently less food mass to counteract the increased energy density, such that the relationship between fat content, energy intake, and weight gain reversed.
All that is to say that a diet consisting of 60% fat by energy appears to be the “sweet spot” at which the increased energy content of food is not sufficiently accounted for by appetite regulation mechanisms to maintain body weight in mice.
What you can do with this information
I’ve said it before and I’ll say it again – stop getting your nutrition advice from the news.
If you’d like to learn more about the role of fats and carbs in the diet, you can read my article, “Do carbs make you fat?”
If you’d like to learn about something more important than fats and carbs, you can check out, “The most overlooked factor in physical transformation”
If you’d like to read about a couple of other nonsense nutrition headlines, you can check out the following articles:
Until next time, have a great week!