Comment on High-fat diets change your brain, not just your body

Matt Davis in Stuff News | September 16, 2019

https://bigthink.com/mind-brain/brain-obesity

Article Summary

In this article, a mouse study from Cell Metabolismis referenced.¹ The key points listed were: 

• Anyone who has tried to change their diet can tell you it’s not as simple as simply waking up and deciding to eat differently.
• New research sheds light on a possible explanation for this; high-fat diets can cause inflammation in the hypothalamus, which regulates hunger.
• Mice fed high-fat diets tended to eat more and become obese due to this inflammation.

While the article headline and the key points focus heavily on the high-fat nature of the diet, the diet was, in fact, a high-fat AND high-carbohydrate diet, or in other words, a good model for the modern, ultra-refined ‘American-style’ diet that forms our food environment.

In mice fed this diet, the microglia of the brain and nervous system were activated, resulting in inflammation in the hypothalamus and this in turn resulted in increased food consumption and obesity. Additionally, the mitochondria (the energy producing ‘powerhouse’ of the cell) of microglia shrunk due to increased production of ‘uncoupling protein 2’.

The reason for this change is a survival one. Quite simply, in times of scarcity (i.e. most of our development as a human species!) it would have been beneficial for the body to encourage us to eat as much energy-dense (and both fat- and carb-dense) food as possible when it was available. However, in the modern food environment of abundance, and a McD’s and Dunkin’ on every corner, this adaptation is… somewhat less beneficial!

Comment

Was the diet actually ‘high fat’?

While the findings of the study are very interesting and incredibly valuable, the focus on the ‘high-fat’ nature of the diet is disappointing. This is a common and frustrating issue in the translation of studies to the mainstream audience, in which ‘high-fat’ diets are often also high in carbohydrate or sugar (especially in animal feeding studies) or in which ‘low-carb’ diets are actually moderate-carb, or mixed macronutrient models, or, in the case of observational studies, simply the lowest-carb consuming participants, who often are the lowest carb-consumers because they are choosing higher-fat and lower-carb junk foods…which are not low-carb per se.

Again, this speaks to a BIG problem in research, that macros are often blamed when in fact, the overall quality of the diet is the bigger factor by far as I have stated with evidence in previous issues of CARR.

What WERE the diets?

I have noticed in various cell metabolism journals that there is little attention paid to the diets given to animal models. There are typically not ‘methods’ sections given, just a longer introduction than we would see in nutrition journals and results from the study. This is frustrating for a nutritional scientist as what constitutes a ‘high-fat’ or ‘high-fat, high-carbohydrate’ diet based on ‘chow’ (standard animal feed given to laboratory animals) could differ by a wide margin and might not, as mentioned earlier, be in any close to what we might consider to be high or low in particular macronutrients in translational nutrition science.

On that note…the problem with animal studies

Look…I’m not one of those guys who dismisses results that I don’t like purely because they come from animal models. Hell, I don’t even dislike these results. BUT we do need to always exercise caution when translating the results from animal studies to humans. In relation to human health, animal studies are meant to inform our understanding of underlying  physiology and processes that might relate to humans. This is because, quite frankly, animals are easier to study, there are fewer ethical constraints, and the food and environment of the animals can be more finely controlled. However, animals such as mice can be quite poor models for some aspects of human physiology, especially as it relates to our responses to changes in macronutrients.

Mice, for example, can be quite poor models for fat-adaptation and ketosis and some strains of mice are particularly poor for this purpose, especially those that have been bred specifically with a higher genetic proclivity towards obesity and diabetes. Humans on the other hand, are typically extremely ‘flexible’ metabolically and can enter and sustain ketosis and increase their relative usage of fats for fuel markedly.

Animal studies should help us to define hypotheses for further research in humans so that we can figure out what the true functional outcomes are for our health. Unfortunately, many science reporters attempt to immediately translate preliminary animal findings into ‘for’ or ‘against’ arguments for particular human diets, and that is simply something that one cannot do based on animal evidence alone.

Outcomes that can be translated to humans must result from a combination of plausibility (the physiological underpinnings of what might be happening, often based in part on in vitro and animal in vivo studies), and demonstrability in controlled trials (which show the ‘true’ effect vs a placebo, but which are often short-term) and longer-term observational evidence (which is uncontrolled and suffers from other potential flaws such as recording and memory bias), typically the only way to see likely very-long-term effects of different diet types or interventions.

Did the negative changes last?

There was a clear effect of the diet on markers of inflammation at 3 and 7 days. However, at 8 weeks all markers had fallen to similar levels to those seen in the control (standard diet) group with some higher, and some lower.

Similarly, the area, number, and overall coverage of mitochondria over the different timepoints was somewhat equivocal with overall reduced area at 8-weeks on the diet vs control, but increased numbers of mitochondria and coverage.

Summary

The evidence is accumulating that an ultra-refined diet (which incidentally is typically high in both carbohydrate and fat) results in inflammation and negative changes to the structures and energy-production of the brain and central nervous system.

Interestingly, in this study, these changes actually appeared to be limited in time, and it will be interesting to see whether those results are mirrored in humans and what implications that might have for the treatment of ‘diabesity’.

It is also unlikely that there would be negative, medium to longer term effects on either glial structures or on inflammation or other risk factors from truly low-carbohydrate diets that are based on a compendium of unrefined foods (in other words, a ‘good’ diet) in humans. Indeed, existing research has demonstrated that gross physical health of the brain might be improved in several ways through the use of low-carb, ketogenic diets (as reported in a previous issue of CARR).

References

1.            Kim JD, Yoon NA, Jin S, Diano S. Microglial UCP2 Mediates Inflammation and Obesity Induced by High-Fat Feeding. Cell Metabolism.