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Effects of Saturated Fat on Mice Behavior

By December 22, 2017August 4th, 2019No Comments

Although lipids are necessary components for sustaining life on this planet, saturated fats can have quite adverse effects.

Saturated fats are becoming more prevalent than ever before as a result of food technology and demand. Something that appears to be good is, in fact, a potential threat. Sure, feel-good foods filled with saturated fats provide temporary pleasure, but in the long-run are dangerous for health and threaten optimal mental functioning.

Mouse models are being used to study the effect of saturated fats on behavior, neuroanatomy, and physiology, in order to create treatments that can be applied to humans and develop our understanding of the connection between the diet and the mind.

Let’s take a closer look at saturated fats, in order to understand what we are dealing with

Saturated Fat Overview

What makes saturated fat so pesky is its structure. In terms of chemical composition, saturated fats are made out of saturated fatty acid chains that are almost entirely comprised out of single bonds, leaving no gaps in the chain and thus giving them the term “saturated”. All fatty acids contain carbon, but when the carbon is surrounded by the maximum amount of hydrogens possible, then that lipid is said to be saturated.

Unfortunately, such tightly packed fatty acid chains can quickly become detrimental to your health. In fact, when they enter the bloodstream, saturated fats inadvertently increase the levels of low-density lipoprotein (LDL), more conventionally known as “bad cholesterol”.

In contrast, unsaturated fats are less packed and will spoil more quickly than saturated fats do. Thus, manufacturers started to produce foods with saturated fats, in order to give the foods a longer shelf life and capitalize on their products.  By hydrogenating the oil, you can create saturated fats which are dense, thick, and would not spoil so easily.

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On the other hand, unsaturated fats increase a different type of cholesterol known as high-density lipoprotein (HDL) which is actually good for your health because it takes LDL to the liver to metabolize it[1].

Saturated fats can be made of many different fatty acids, but the type that is most commonly found in our foods is palmitic acid. More on this later.

Pizza, cheese, burgers, ice-cream, and pastries are common to the U.S. diet and are all packed with a high percentage of saturated fat[2]. Next time you want to order pizza, think twice. Such choices and dietary intake will create an impact on the individual and society over time and thus need to be studied through the use of animal models.

Note: Most foods contain some proportion out of the many different types of fats (saturated, polyunsaturated, and monounsaturated), so it is impossible to completely omit saturated fats from your diet. You must simply omit the foods that have too much of saturated fats.

Saturated Fats Affect the Nervous System

Now, it may be obvious that eating overly fatty foods may negatively impact your cholesterol as well as other organs. What is less evident is the fact that foods high in saturated fats will negatively affect the nervous system. In fact, emotion, cognition, and behavior are all impacted by a high fat diet (HFD) to such an extent that you can actually observe and measure the subsequent changes.

Psychological conditions such as depression and anxiety have been connected with the HFD diets and obesity. In addition to the behavioral manifestations of anxiety and depressions, obesity is associated with an increase in neuroinflammation, higher oxidative stress, and decreased neurogenesis[3]. More on this later.

To study the effect of diet on neurophysiology and behavior, scientists combine behavioral measurement tools such as maze apparatuses with molecular testing techniques such as western blots or gas chromatography.

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How They Were Tested

A multitude of studies has been conducted exploring the connection between diet and cognition. We will focus on two:

  • High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behavior by Sharma, Zhuang, and Gomez-Pinilla
  • The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice by Moon et al.

Switching From DHA to HFD Diet Leads to Biological and Behavioral Alterations

In 2012, Sharma, Zhuang, and Gomez-Pinilla demonstrated that mice began changing both biologically and behaviorally after switching from an n-3 enriched fatty acid diet  (more commonly known as the DHA-diet) to HFD. This leads to an increase in anxiety-like behaviors, changes in their stress response, and creates a decreased affinity for neuroplasticity.

To reach these conclusions and get a better understanding of the effects of saturated fats on mice, they used a wide range of tools and techniques.

Western blot tests were used to assess the proteins and molecules which were of interest to the study. A DHA-diet is linked to cognitive strength, supporting plasticity-related molecules. Thus, to test the impact of HFD upon weaning from a DHA-diet, the molecules and brain regions associated with cognition were chosen as areas of interest, namely:

  • Brain-derived neurotrophic factors (BDNF)
  • cAMP response element binding protein (CREB)
  • Neuropeptide Y (NPY)
  • GAP-43 protein
  • phospho-CaMKII
  • p-TrkB

These proteins and plasticity markers were measured for both the hippocampus and the frontal cortex.

Blood samples were used to assess how HFD impacts the body’s physiology by analyzing for the following metabolic markers:

  • Glucose
  • Cholesterol
  • Triglycerides
  • Uric acid

Elevated plus maze and open field apparatus were used to observe anxiety-like behaviors in the mice.

The results of the elevated plus maze were correlated with hippocampal activity. The amount of p-CREB in the hippocampus positively correlated with how many entries were made (r=0.6189; p<0.05) indicating a more explorative nature as opposed to one confined by fear and anxiety.

In addition to the hippocampus, the frontal cortex’s p-CREB proteins were also positively correlated with the distance the mice traveled (r=0.6908; p<0.001) suggesting that the neuronal system which exists between the hippocampus and frontal cortex is greatly impacted by dietary changes

Also, BDNF concentrations in the frontal cortex and hippocampus were positively correlated with the distance covered in the open field apparatus as well as other outcomes. The increase in BDNF is important because this neurochemical is implicated in brain health, plasticity, and learning. So, having lower concentrations of BDNF concentrations in the HFD condition may account for the observable changes in cognition and behavior.

Gas chromatography was used to study fatty acids. Naturally, the brain contains a wide range of fatty acids. However, the distribution of those fatty acids which will change in accordance with the type of diet that was administered. So, gas chromatography was used to determine the distribution of numerous fatty acids within each of the feeding conditions.

Effect of saturated fats is quickly detectable

A different experimental design measured the neurotransmitters at 24-hours post injection of fatty acids and found significant differences in dopamine (DA) and serotonin (5-HT) as when compared to baseline.

DA and 5-HT are both implicated in emotion and learning, so observing their changes during a controlled experiment is a significant implication of the effects saturated fats have on behavior.  

The researchers derived their samples after preparing the mice brains for testing. To determine the actual levels of DA and 5-HT, along a plethora of other neurochemicals, the team used high-performance liquid chromatography (HPLC) (Moon et. al, 2014).

The apparatuses and experimental paradigms used to observe how the administration of HFD impacted the organism’s behaviors on a short-term basis were:

In addition to affecting the learning and memory systems by impacting the amygdala and the neurotransmitters DA and 5-HT, HFD also affects systems responsible for plasticity, as well as the hypothalamic-pituitary-adrenal (HPA) axis’  response to stressors.

Impact of saturated fats on plasticity and the stress response.

As outlined earlier, the study by Sharma, Zhuang, and Gomez-Pinilla demonstrates that the plasticity and stress responses are negatively affected just by switching diet intake from unsaturated fats to saturated fats.

Feeding rats HFD decreased the modulating ability of the NPY1 receptor in both the hippocampus (35.5%, p<0.05) and the frontal cortex (22%, p<0.05)[3]. Such a decrease is significant because NPY is implicated in lowering anxiety responses. Thus, its decrease would indicate heightened anxiety responses and behaviors.

Another example included pCREB, a phosphorylated molecule that is implicated in the perpetuation of the BDNF signaling pathway. Rats in the HFD condition had a very low amount of pCREB in both the hippocampus (15.33%, p<0.05) and the frontal cortex (29.22%, p<0.0001).

Translational research

What is known

Whenever anxiety and depression are put into question, diet is one of the first things addressed, thus demonstrating the clinical relevance between food intake and mental functioning.

HFD diets are very high in palmitic acid, a specific type of free fatty acid. Though the biological traces have been reported for this and free fatty acid has been known for quite some time, only recently was the connection made between behavior and cognition. So, plasma concentrations derived from people with HFD diets will be high in palmitic acid[4].

The adverse effects of HFD are frequently contrasted with the positive effects of omega-3 polyunsaturated fatty acids. While the saturated fats from HFD are associated with the likelihood of depression and anxiety, the intake of omega-3 polyunsaturated fatty acids is connected to antidepressant effects[3].

In terms of physiology, injury and atrophy in the hippocampus are also observed in adults that are suffering from diabetes and consuming a high fat diet[5].

In one of the animal studies outlined previously, a significant change in behavior included a decrease in the amount of distance traveled. Similarly, obesity is associated with decreased motor movement in humans[6].

As demonstrated earlier in the animal experiments, an HFD diet decreases their TrkB levels, a protein important for plasticity signaling. Human psychiatric illnesses are also linked with lower TrkB levels[7].

What still remains a mystery

More information needs to be conducted outlining and revealing the impact of saturated fatty acids on brain health and the subsequent behaviors. Though certain impacts have been clearly demonstrated, such as the decrease of BDNF, the precise mechanisms behind the effects that are associated with saturated fats still remain largely unknown.


The impact of saturated fats is much more serious and deeper than initially believed, reaching the depths of human psychology and impacting both behaviors and mental processes.

Saturated fats can negatively impact an organism. Just 24 hours after consuming saturated fats, differences can be observed in both behaviors and neurotransmitters.

Furthermore, even a good history concerning your dietary choices isn’t enough to protect you from the effects following prolonged HFD consumption.

Animal models are being used in junction with apparatuses to study and observe behavior and then other advanced techniques are being applied to determine the molecular mechanisms.

The mechanisms observed in animal studies are slowly being translated over into human studies aiming to demonstrate just why mood, cognition, and behavior are all negatively impacted by saturated fats.


  1. “Fatty Acids.” HOPES Huntington’s Disease Information, Stanford, 11 Feb. 2017, Accessed 29 Aug. 2017.
  2. “Top Food Sources of Saturated Fat in the U.S.” The Nutrition Source, Harvard, 27 Feb. 2017, Accessed 29 Aug. 2017
  3. Sharma, Sandeep, Yumei Zhuang, and Fernando Gomez-Pinilla. “High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behavior.” Scientific reports 2 (2012): 431.
  4. Moon, Morgan L., et al. “The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice.” Metabolism 63.9 (2014): 1131-1140.
  5. Mueller, Karsten, et al. “Overweight and obesity are associated with neuronal injury in the human cerebellum and hippocampus in young adults: a combined MRI, serum marker and gene expression study.” Translational Psychiatry 2.12 (2012): e200.
  6. Wang, Chuanming, et al. “Obesity reduces cognitive and motor functions across the lifespan.” Neural plasticity 2016 (2016).
  7. Duman, Ronald S., and Lisa M. Monteggia. “A neurotrophic model for stress-related mood disorders.” Biological Psychiatry 59.12 (2006): 1116-1127.
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