High-fat diets affect your brain, not just your physical appearance

Summary: High-fat diets are not only bad for your waistline, they are also bad for your brain health. A new study reveals high-fat diets contribute to hypothalamic inflammation which occurs long before symptoms of obesity arise.

Source: Yale

Much research has pointed to how an unhealthy diet correlates to obesity but has not explored how diet can bring about neurological changes in the brain. A recent Yale study has discovered that high-fat diets contribute to irregularities in the hypothalamus region of the brain, which regulates body weight homeostasis and metabolism.

Led by Sabrina Diano, the Richard Sackler Family Professor of Cellular & Molecular Physiology and professor of neuroscience and comparative medicine, the study evaluated how the consumption of a high-fat diet — specifically diets that include high amounts of fats and carbohydrates — stimulates hypothalamic inflammation, a physiological response to obesity and malnutrition.

The researchers reaffirmed that inflammation occurs in the hypothalamus as early as three days after consumption of a high-fat diet, even before the body begins to display signs of obesity. “We were intrigued by the fact that these are very fast changes that occur even before the body weight changes, and we wanted to understand the underlying cellular mechanism,” said Diano who is also a member of the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism.

The researchers observed hypothalamic inflammation in animals on a high fat diet and discovered that changes in physical structure were occurring among the microglial cells of animals. These cells act as the first line of defense in the central nervous system that regulate inflammation. Diano’s lab found that the activation of the microglia was due to changes in their mitochondria, organelles that help our bodies derive energy from the food we consume. The mitochondria were substantially smaller in the animals on a high-fat diet. The mitochondria’s change in size was due to a protein, Uncoupling Protein 2 (UCP2), which regulates the mitochondria’s energy utilization, affecting the hypothalamus’ control of energy and glucose homeostasis.

The UCP2-mediated activation of microglia affected neurons in the brain that, when receiving an inflammatory signal due to the high fat diet, stimulated the animals in the high-fat diet group to eat more and become obese. However, when this mechanism was blocked by removing the UCP2 protein from microglia, animals exposed to a high fat diet ate less and were resistant to gain weight.

This shows a burger and fries
The researchers observed hypothalamic inflammation in animals on a high fat diet and discovered that changes in physical structure were occurring among the microglial cells of animals. The image is in the public domain.

The study not only illustrates how high-fat diets affect us physically, but conveys how an unhealthy diet can alter our food intake neurologically. “There are specific brain mechanisms that get activated when we expose ourselves to specific type of foods. This is a mechanism that may be important from an evolutionary point of view. However, when food rich in fat and carbs is constantly available it is detrimental.”

Diano’s long-standing goal is to understand the physiological mechanisms that regulate how much food we consume, and she continues to perform research on how activated microglia can affect various diseases in the brain, including Alzheimer’s disease, a neurological disorder that is associated with changes in the brain’s microglial cells and has been shown to have higher incidence among obese individuals.

About this neuroscience research article

Media Contacts:
Jami LaRue – Yale
Image Source:
The image is in the public domain.

Original Research: Closed access
“Microglial UCP2 Mediates Inflammation and Obesity Induced by High-Fat Feeding”. Jung Dae Kim, Nal Ae Yoon, Sungho Jin, Sabrina Diano.
Cell Metabolism doi:10.1016/j.cmet.2019.08.010


Microglial UCP2 Mediates Inflammation and Obesity Induced by High-Fat Feeding

• HFD induces a dynamic increase of Ucp2 mRNA in hypothalamic microglia
• HFD induces functional and morphological changes in arcuate microglial mitochondria
• UCP2 is required for HFD-induced mitochondrial changes in hypothalamic microglia
• UCP2 is required for HFD-induced inflammation, obesity, and POMC synaptic plasticity

Microglia play a crucial role in immune responses, including inflammation. Diet-induced obesity (DIO) triggers microglia activation and hypothalamic inflammation as early as 3 days after high-fat diet (HFD) exposure, before changes in body weight occur. The intracellular mechanism(s) responsible for HFD-induced microglia activation is ill defined. Here, we show that in vivo, HFD induced a rapid and transient increase in uncoupling protein 2 ( Ucp2) mRNA expression together with changes in mitochondrial dynamics. Selective microglial deletion of Ucp2 prevented changes in mitochondrial dynamics and function, microglia activation, and hypothalamic inflammation. In association with these, male and female mice were protected from HFD-induced obesity, showing decreased feeding and increased energy expenditure that were associated with changes in the synaptic input organization and activation of the anorexigenic hypothalamic POMC neurons and astrogliosis. Together, our data point to a fuel-availability-driven mitochondrial mechanism as a major player of microglia activation in the central regulation of DIO.

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  1. Your article about High Fat Diets affecting the brain, not just physical appearance, is misleading, with your picture of a super high carbohydrate meal. Also, the meat could be turkey or veggie burger, but the bread and fries are junk food. I stay very slim and cognitively alert on a high “good” fat, vegetable, and grass fed beef diet.

  2. This is extremely irresponsible journalism! The study showed not just a diet high in fat, but also in carbs. So the headline should be high-fat and carb diets are detrimental!

  3. A bit confusing, since quotes are in regards to the consumption of high fat AND carbohydrates specifically. Seems odd to villainize the fat when the carbs are major contributors… I’m assuming this study does not relate to high-fat, low-carb diets such as Keto?

  4. In my opinion Laughable rubbish. The opening statement – the summary states – fats – not only bad for the waistline.. Well stop right there. Are people being paid for this nonsense. Since going on a high fat diet I have lost 66 lbs with ease in 10 months. Rather than waste their time researching fats and then coming to an incorrect conclusion they should put their skills to researching sugars and carbohydrates, because thats where the weight and disease comes from. Whilst they are doing that, they should also research a person Dr Ansell Keyes, and his research, since proven to be ” somewhat doctored “.
    Gee these types of articles make me mad !!!

  5. The title is misleading . It isn’t “high fat diets” that cause the issue! The research was “high fat PLUS high carb.” the Title of this article is misleading and a misrepresentation of fact. Shane on you Neuroscience News!

    You have jumped on the sensationalized news bandwagon – you are using a title in an attempt to use the recent popularity of high fat – low carb diets to get persons to read an article that appears to speak about a “keto” diet when in fact the sucks is not related to a keto type diet at all.

    This is the shameful state of the US national media.

  6. The title of this article is misleading click-bait. As someone who is currently doing a keto diet I try to keep up with as much of the science behind high fat diets as possible for my health and out of curiosity.

    The study specifically states the diet it focused on was high fat, high carbohydrate. This would be like having an article title, ‘Milk makes you fat, study shows!’ and then the study cited talks about how they gave participants lots of milk and cookies and they got fat.

    Why not, ‘High fat, high carbohydrate diet affects your brain as well as your waistline’? I mean, why ignore one of the two macronutrients that study participants get high amounts of?

  7. If the Yale study included “specifically diets that include high amounts of fats and carbohydrates”, what was done to isolate the effect of fat on the inflammatory response? Inflammation is common in ‘low fat/high carbohydrate’ diets, so what evidence led the researchers to attribute the result to fat vs. carbohydrate? The results as presented seem to describe a study in which a major confounder is totally ignored and the observed effect attributed without adequately discriminating between the two major components of the diet.

  8. The photo shows burgers and fries. What defines a high fat diet? My “HFD” IS NO FRIES, NO BUNS, NO KETCHUP, MORE dark leafy greens, but ithe low carb aspect may define it as high fat. Yet my diet has reduced inflamation and increased stability in blood sugar. Plus that burger is not as frequent a fat source as olive oil….what is the REALpurpose of this study? Who funded it?

  9. This is one of the more deceptive articles I’ve read in awhile.

    First off, the food shown in the picture is junk food…of course it caused inflammation and an expanding waist. Junk carbs, bad fats, and low quality meats are all a problem.

    Fats are not created equal. Grass fed meat has a different fat composition than grain fed meats. Fries cooked in polyunsaturated fatty acids are different than fries cooked in lard. The fat in “marbled” meat comes from inflammation and leads to inflammation.

    And the article is titled to make people think that the weight gain came from a high fat diet, but buried in the article, it says that it came from a high fat AND high carb diet.

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