Tag: high-fat diet

Categories : Diet and Nutrition Mental HealthTags :

High-fat Diets can Interfere with Serotonin Pathways, Fuelling Anxiety

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Photo by Jonathan Borba

New research from CU Boulder shows that turning to junk food when we’re stressed out may backfire. The study found that in animals, a high-fat diet disrupts resident gut bacteria, alters behaviour and, through a complex pathway connecting the gut to the brain, influences brain chemicals in ways that fuel anxiety.

“Everyone knows that these are not healthy foods, but we tend to think about them strictly in terms of a little weight gain,” said lead author Christopher Lowry, a professor of integrative physiology at CU Boulder. “If you understand that they also impact your brain in a way that can promote anxiety, that makes the stakes even higher.”

For the study, published in the journal Biological Research in May, Lowry worked with first author Sylvana Rendeiro de Noronha, a doctoral student at the Federal University of Ouro Preto in Brazil.

In a previous study, the team found that rats fed a high-fat diet consisting primarily of saturated fat showed increases in neuroinflammation and anxiety-like behaviour.

While evidence is mixed, some human studies have also shown that replacing a high-fat, high-sugar, ultra-processed diet with a healthier one can reduce depression and anxiety.

The dark side of serotonin

To better understand what may be driving the fat-anxiety connection, Lowry’s team divided male adolescent rats into two groups: Half got a standard diet of about 11% fat for nine weeks; the others got a high-fat diet of 45% fat, consisting mostly of saturated fat from animal products.

The typical American diet is about 36% fat, according to the Centers for Disease Control and Prevention.

Throughout the study, the researchers collected faecal samples and assessed the animals’ gut microbiome. After nine weeks, the animals underwent behavioural tests.

When compared to the control group, the group eating a high-fat diet, not surprisingly, gained weight. But the animals also showed significantly less diversity of gut bacteria. Generally speaking, more bacterial diversity is associated with better health, Lowry explained. They also hosted far more of a category of bacteria called Firmicutes and less of a category called Bacteroidetes. A higher Firmicutes to Bacteroidetes ratio has been associated with the typical industrialised diet and with obesity.

The high-fat diet group also showed higher expression of three genes (tph2, htr1a, and slc6a4) involved in production and signalling of the neurotransmitter serotonin – particularly in a region of the brainstem known as the dorsal raphe nucleus cDRD, which is associated with stress and anxiety.

While serotonin is often billed as a “feel-good brain chemical,” Lowry notes that certain subsets of serotonin neurons can, when activated, prompt anxiety-like responses in animals. Notably, heightened expression of tph2, or tryptophan hydroxylase, in the cDRD has been associated with mood disorders and suicide risk in humans.

“To think that just a high-fat diet could alter expression of these genes in the brain is extraordinary,” said Lowry. “The high-fat group essentially had the molecular signature of a high anxiety state in their brain.”

A primal gut-brain connection

Just how a disrupted gut can change chemicals in the brain remains unclear. But Lowry suspects that an unhealthy microbiome compromises the gut lining, enabling bacteria to slip into the body’s circulation and communicate with the brain via the vagus nerve, a pathway from the gastrointestinal tract to the brain.

“If you think about human evolution, it makes sense,” Lowry said.  “We are hard-wired to really notice things that make us sick so we can avoid those things in the future.”

Lowry stresses that not all fats are bad, and that healthy fats like those found in fish, olive oil, nuts and seeds can be anti-inflammatory and good for the brain.

But his research in animals suggests that exposure to an ultra-high-fat diet consisting of predominantly saturated fats, particularly at a young age, could both boost anxiety in the short-term and prime the brain to be more prone to it in the future.

His advice: Eat as many different kinds of fruits and vegetables as possible, add fermented foods to your diet to support a healthy microbiome and lay off the pizza and fries. Also, if you do have a hamburger, add a slice of avocado. Research shows that good fat can counteract some of the bad.

Rodrigo Cunha de Menezes, professor of physiology at Federal University of Ouro Preto in Brazil, is co- senior author on this paper.

Source: University of Colorado Boulder

Categories : Diet and Nutrition Immune SystemTags :

Yet Another Impact of High-fat Diets: Immune Changes

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Photo by Patrick Fore on Unsplash

A new study from UC Riverside has added more reasons to stick to New Year’s diet resolutions: it showed that that high-fat diets affect genes linked not only to obesity, colon cancer and irritable bowels, but also to the immune system, brain function, and potentially COVID risk.

While other studies have examined the effects of a high-fat diet, this one is unusual in its scope. UCR researchers fed mice three different diets over the course of 24 weeks where at least 40% of the calories came from fat. Then, they looked not only at the microbiome, but also at genetic changes in all four parts of the intestines.

One group of mice ate a diet based on saturated fat from coconut oil, another got a monounsaturated, modified soybean oil, a third got an unmodified soybean oil high in polyunsaturated fat. Compared to a low-fat control diet, all three groups experienced concerning changes in gene expression, the process that turns genetic information into a functional product, such as a protein.

Plant-based or not, high-fat is bad

“Word on the street is that plant-based diets are better for you, and in many cases that’s true. However, a diet high in fat, even from a plant, is one case where it’s just not true,” said Frances Sladek, a UCR cell biology professor and senior author of the new study.

The study, published in Scientific Reports, documents the many impacts of high-fat diets. Some of the intestinal changes did not surprise the researchers, such as major changes in genes related to fat metabolism and the composition of gut bacteria. For example, they observed an increase in pathogenic E. coli and a suppression of Bacteroides, which helps protect the body against pathogens.

Other observations were more surprising, such as changes in genes regulating susceptibility to infectious diseases. “We saw pattern recognition genes, ones that recognise infectious bacteria, take a hit. We saw cytokine signalling genes take a hit, which help the body control inflammation,” Sladek said. ‘So, it’s a double whammy. These diets impair immune system genes in the host, and they also create an environment in which harmful gut bacteria can thrive.”

The team’s previous work with soybean oil documents its link to obesity and diabetes, both major risk factors for COVID. This paper now shows that all three high-fat diets increase the expression of ACE2 and other host proteins that are used by COVID spike proteins to enter the body.

Additionally, the team observed that high-fat food increased signs of stem cells in the colon. “You’d think that would be a good thing, but actually they can be precursors to cancer,” Sladek said.

In terms of effects on gene expression, coconut oil showed the greatest number of changes, followed by the unmodified soybean oil. Differences between the two soybean oils suggest that polyunsaturated fatty acids in unmodified soybean oil, primarily linoleic acid, play a role in altering gene expression.

Negative changes to the microbiome in this study were more pronounced in mice fed the soybean oil diet. This was unsurprising, as the same research team previously documented other negative health effects of high soybean oil consumption.

Soybeans are fine, but watch the oil

In 2015, the team found that soybean oil induces obesity, diabetes, insulin resistance, and fatty liver in mice. In 2020, the researchers team demonstrated the oil could also affect genes in the brain related to conditions like autism, Alzheimer’s disease, anxiety, and depression.

Interestingly, in their current work they also found the expression of several neurotransmitter genes were changed by the high fat diets, reinforcing the notion of a gut-brain axis that can be impacted by diet.

The researchers have noted that these findings only apply to soybean oil, and not to other soy products, tofu, or soybeans themselves. “There are some really good things about soybeans. But too much of that oil is just not good for you,” said UCR microbiologist Poonamjot Deol, who was co-first author of the current study along with UCR postdoctoral researcher Jose Martinez-Lomeli.

Also, the studies were conducted using mice, and mouse studies do not always translate to the same results in humans. However, humans and mice share 97.5% of their working DNA. Therefore, the findings are concerning, as soybean oil is the most commonly consumed oil in the United States, and is increasingly being used in other countries, including Brazil, China, and India.

By some estimates, Americans tend to get nearly 40% of their calories from fat, which mirrors what the mice were fed in this study. “Some fat is necessary in the diet, perhaps 10 to 15%. Most people though, at least in this country, are getting at least three times the amount that they need,” Deol said.

Readers should not panic about a single meal. It is the long-term high-fat habit that caused the observed changes. Recall that the mice were fed these diets for 24 weeks. “In human terms, that is like starting from childhood and continuing until middle age. One night of indulgence is not what these mice ate. It’s more like a lifetime of the food,” Deol said.

That said, the researchers hope the study will cause people to closely examine their eating habits.

Source: University of California – Riverside

Categories : Diet and Nutrition Metabolic DisordersTags : Leave a comment

Diet Extremes of Carbohydrate and Fat Tied to Sex-specific Mortality Risks

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Photo by I Yunmai on Unsplash

New research suggests that extreme dietary habits involving carbohydrates and fats affect life expectancy. Results published in The Journal of Nutrition show that a low carbohydrate intake in men and a high carbohydrate intake in women are associated with a higher risk of all-cause and cancer-related mortality and that women with higher fat intake may have a lower risk of all-cause mortality. Their findings suggest that people should pursue a balanced diet rather than heavily restricting their carbohydrate or fat intake.

While low-carbohydrate and low-fat diets are becoming popular as a way to promote weight loss and improve blood glucose levels, their long-term effects on life expectancy are less clear. Interestingly, recent studies conducted in Western countries suggest that extreme dietary habits for carbohydrates and fats are associated with a higher risk of mortality. However, few studies have explored these associations in East Asian populations, including Japanese individuals who typically have relatively low fat and high-carbohydrate dietary intakes.

Researchers from Nagoya University Graduate School of Medicine in Japan led by Dr Takashi Tamura conducted a follow-up survey over a period of 9 years with 81 333 Japanese people (34,893 men and 46 440 women) to evaluate the association between carbohydrate and fat intakes and the risk of mortality. Daily dietary intakes of carbohydrates, fats, and total energy were estimated using a food frequency questionnaire and calculated as a percentage of total energy intake for carbohydrates and fats. Carbohydrate intake quality (ie, refined compared with minimally processed carbohydrate intake) and fat intake quality (ie, saturated compared with unsaturated fat intake) were also assessed to examine the impact of food quality on the association with mortality.

They found that men who consumed less than 40% of their total energy from carbohydrates experienced significantly higher risks of all-cause and cancer-related mortality. The trend was observed regardless of whether refined or minimally processed carbohydrate were considered. On the other hand, among women with 5 years or longer of follow-up, those with a high carbohydrate intake of more than 65% had a higher risk of all-cause mortality. No clear association was observed between refined or minimally processed carbohydrate intake and the risk of mortality in women.

For fats, men with a high fat intake of more than 35% of their total energy from fats had a higher risk of cancer-related mortality. They also found that a low intake of unsaturated fat in men was associated with a higher risk of all-cause and cancer-related mortality. In contrast, total fat intake and saturated fat intake in women showed an inverse association with the risk of all-cause and cancer-related mortality. They concluded that this finding does not support the idea that high fat intake is detrimental to longevity in women.

“The finding that saturated fat intake was inversely associated with the risk of mortality only in women might partially explain the differences in the associations between the sexes,” Dr Tamura stated. “Alternatively, components other than fat in the food sources of fat may be responsible for the observed inverse association between fat intake and mortality in women.”

This study is extremely important because restricting carbohydrates and fats, such as extremely low-carbohydrate and low-fat diets, are now popular dieting strategies aimed at improving health, including the management of metabolic syndrome. However, this study shows that low-carbohydrate and low-fat diets may not be the healthiest strategy for promoting longevity, as their short-term benefits could potentially be outweighed by long-term risk.

Overall, an unfavourable association with mortality was observed for low-carbohydrate intake in men and for high carbohydrate intake in women, whereas high fat intake could be associated with a lower mortality risk in women. The findings suggest that individuals should carefully consider how to balance their diet and ensure that they are taking in energy from a variety of food sources, while avoiding extremes.

Source: Nagoya University

Categories : Cancer GastrointestinalTags : Leave a comment

How High-fat Diets Affect Gut Bacteria and Increase Colorectal Cancer Risk

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

The increasing rate of obesity and high-fat diets are suspected to be behind the growing rates of colorectal cancers in people aged under 50. Now, in a study published in Cell Reports, researchers at have discovered how high-fat diets can change gut bacteria and alter digestive molecules called bile acids that are modified by those bacteria, predisposing mice to colorectal cancer.

In the study, researchers from the Salk Institute and UC San Diego found increased levels of specific gut bacteria in mice fed high-fat diets. They showed that those gut bacteria alter the composition of the bile acid pool in ways that cause inflammation and affect the replenishment rate of intestinal stem cells replenish.

“The balance of microbes in the gut is shaped by diet, and we are discovering how alterations in the gut microbial population (the gut microbiome) can create problems that lead to cancer,” says co-senior author and Professor Ronald Evans, director of Salk’s Gene Expression Laboratory. “This paves the way toward interventions that decrease cancer risk.”

In 2019, Evans and his colleagues showed in mice how high-fat diets boosted the overall bile acid levels. The shift in bile acids, they found, shut down a key protein in the gut, the Farnesoid X receptor (FXR). and increased the prevalence of cancer.

However, there were still missing links in the story, including how the gut microbiome and bile acids are changed by high-fat diets.

In the new work, Evans’ group teamed up with the labs of Rob Knight and Pieter Dorrestein at UC San Diego to examine the microbiomes and metabolomes (collections of dietary and microbially derived small molecules) in the digestive tracks of animals on high-fat diets. They studied mice genetically more susceptible to colorectal tumours.

The scientists discovered that although mice fed high-fat diets had more bile acids in their guts, it was a less diverse collection with a higher prevalence of certain bile acids that had been changed by gut bacteria. They also showed that these modified bile acids affected the proliferation of stem cells in the intestines. Without frequent replenishment, they accumulate mutations – a key step toward encouraging the growth of cancers, which often arise from these stem cells.

“We are only just beginning to understand these bacterially-conjugated bile acids and their roles in health and disease,” says co-author Michael Downes, a staff scientist at Salk.

There were also striking differences in the microbiomes of the mice on high-fat diets: the collections of gut bacteria in these mice’s digestive tracts were less diverse and contained different bacteria than the microbiomes of mice not on high-fat diets. Two of these bacteria – Ileibacterium valens and Ruminococcus gnavus – were able to produce these modified bile acids.

The scientists were surprised to discover that a high-fat diet actually had a greater impact on the microbiome and modified bile acids than a genetic mutation that increases cancer susceptibility in the animals.

“We’ve pinpointed how high-fat diet influences the gut microbiome and reshapes the bile acids pool, pushing the gut into an inflamed, disease-associated state,” says co-first author Ting Fu, a former postdoctoral fellow in the Evans lab.

The researchers believe high-fat diets change the composition of the microbiome, encouraging the growth of bacteria like I. valens and R. gnavus. In turn, that boosts levels of modified bile acids. In a vicious cycle, those bile acids create a more inflammatory environment that can further change the makeup of gut bacteria.

“We’ve deconstructed why high-fat diets aren’t good for you, and identified specific strains of microbes that flare with high-fat diets,” says Evans, March of Dimes Chair in Molecular and Developmental Biology. “By knowing what the problem is, we have a much better idea of how to prevent and reverse it.”

In the future, the team will study how quickly the microbiome and bile acids change after an animal begins eating a high-fat diet. They also plan to study ways to reverse the cancer-associated effects of a high-fat diet by targeting FXR – the protein that they previously discovered to be associated with bile acid changes.

Source: Salk Institute

Categories : Diet and Nutrition NeurologyTags : Leave a comment

High-fat Diets Overload the Ability to Moderate Calorie Intake

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Regularly eating a high fat/calorie diet could reduce the brain’s ability to regulate calorie intake, according to a study published in The Journal of Physiology. Rat studies revealed a signalling pathway which causes a quick response to high fat/high calorie intake, reducing food and calorie intake. But continuously eating a high fat/calorie diet seems to disrupt this signalling pathway, sabotaging this short-term protection.

Senior author Dr Kirsteen Browning said, “Calorie intake seems to be regulated in the short-term by astrocytes. We found that a brief exposure (three to five days) of high fat/calorie diet has the greatest effect on astrocytes, triggering the normal signalling pathway to control the stomach. Over time, astrocytes seem to desensitise to the high fat food. Around 10–14 days of eating high fat/calorie diet, astrocytes seem to fail to react and the brain’s ability to regulate calorie intake seems to be lost. This disrupts the signalling to the stomach and delays how it empties.”

Astrocytes initially react when high fat/calorie food is ingested, triggering the release of gliotransmitters, chemicals (including glutamate and ATP) that excite nerve cells and enable normal signalling pathways to stimulate neurons that control stomach function. This ensures the stomach contracts correctly to fill and empty in response to food passing through the digestive system. When astrocytes are inhibited, the cascade is disrupted. The decrease in signalling chemicals leads to a delay in digestion because the stomach doesn’t fill and empty appropriately.

The vigorous investigation used behavioural observation to monitor food intake in rats which were fed a control or high fat/calorie diet for one, three, five or 14 days. This was combined with pharmacological and specialist genetic approaches (both in vivo and in vitro) to target distinct neural circuits, which enabled the researchers to specifically inhibit astrocytes in a particular region of the brainstem. In this way, they assessed the response of individual neurons.

Human studies will need to be carried out to confirm if the same mechanism occurs in humans. If this is the case, further testing will be required to assess if the mechanism could be safely targeted without disrupting other neural pathways.

The researchers have plans to further explore the mechanism. Dr Browning said, “We have yet to find out whether the loss of astrocyte activity and the signalling mechanism is the cause of overeating or that it occurs in response to the overeating. We are eager to find out whether it is possible to reactivate the brain’s apparent lost ability to regulate calorie intake. If this is the case, it could lead to interventions to help restore calorie regulation in humans.”

Source: The Physiological Society

Categories : Metabolic Disorders Pain ManagementTags : Leave a comment

High-fat Diet can Cause Pain Sensitivity without Obesity or Diabetes

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Woman holding her wrist in pain

A new study using a mouse model suggests that a short-term exposure to a high-fat diet may be linked to pain sensations, such as from a light touch, even without a prior injury or a pre-existing condition like obesity or diabetes. This finding may help in part explain the severity of the opioid crisis.

The study, published in Scientific Reports, compared the effects of eight weeks of different diets on two cohorts of mice. One group received normal chow, while the other was fed a high-fat diet in a way that did not precipitate the development of obesity or high blood sugar, both of which are conditions that can result in diabetic neuropathy and other types of pain.

The researchers found that the high-fat diet induced hyperalgesic priming – a neurological change that represents the transition from acute to chronic pain – and allodynia, which is pain resulting from stimuli that do not normally provoke pain.

“This study indicates you don’t need obesity to trigger pain; you don’t need diabetes; you don’t need a pathology or injury at all,” said Dr Michael Burton, assistant professor of neuroscience and corresponding author of the article. “Eating a high-fat diet for a short period of time is enough – a diet similar to what almost all of us in the US eat at some point.”

The study also compared obese, diabetic mice with those that just experienced dietary changes.

“It became clear, surprisingly, that you don’t need an underlying pathology or obesity. You just needed the diet,” Burton said. “This is the first study to demonstrate the influential role of a short exposure to a high-fat diet to allodynia or chronic pain.”

Diet itself caused markers of neuronal injury.

Western diets are rich in fats – in particular saturated fats, which have proved to be responsible for an epidemic of obesity, diabetes and associated conditions. Individuals who consume high amounts of saturated fats – like butter, cheese and red meat – have high amounts of free fatty acids circulating in their bloodstream that in turn induce systemic inflammation.

Recently, scientists have shown that these high-fat diets also increase existing mechanical pain sensitivity in the absence of obesity, and that they can also aggravate pre-existing conditions or imped injury recovery. To date, no studies have explained how high-fat diets alone can be a sensitising factor in inducing pain from nonpainful stimuli, such as a light touch on the skin, Burton said.

“We’ve seen in the past that, in models of diabetes or obesity, only a subsection of the people or animals experience allodynia, and if they do, it varies across a spectrum, and it isn’t clear why,” Burton said. “We hypothesized that there had to be other precipitating factors.”

The researchers examined blood levels of fatty acids in the mice. They found that a fatty acid called palmitic acid, the most common saturated fatty acid in animals, binds to a particular receptor on nerve cells, a process that results in inflammation and mimics injury to the neurons.

“The metabolites from the diet are causing inflammation before we see pathology develop,” Burton said. “Diet itself caused markers of neuronal injury.

The mechanism behind this transition is important because it is the presence of chronic pain – from whatever source – that is fuelling the opioid epidemic

“Now that we see that it’s the sensory neurons that are affected, how is it happening? We discovered that if you take away the receptor that the palmitic acid binds to, you don’t see that sensitising effect on those neurons. That suggests there’s a way to block it pharmacologically.”

Burton said the next step will be to focus on the neurons themselves – how they are activated and how injuries to them can be reversed. It is part of a larger effort to understand better the transition from acute to chronic pain.

“The mechanism behind this transition is important because it is the presence of chronic pain – from whatever source – that is fuelling the opioid epidemic,” he said. “If we figure out a way to prevent that transition from acute to chronic, it could do a lot of good.”

Burton said he hopes his research encourages health care professionals to consider the role diet plays in influencing pain.

“The biggest reason we do research like this is because we want to understand our physiology completely,” he said. “Now, when a patient goes to a clinician, they treat a symptom, based off of an underlying disease or condition. Maybe we need to pay more attention to how the patient got there: Does the patient have diabetes-induced or obesity-induced inflammation; has a terrible diet sensitised them to pain more than they realized? That would be a paradigm shift.”

Source: University of Texas at Dallas

Categories : Cancer Diet and NutritionTags : Leave a comment

High-fat Diets Increase Nitric Oxide, a Cancer Promoter

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A hamburger
Photo by Ilya Mashkov on Unsplash

Research which appears in ACS Central Science has shown that a direct link exists between the amount of fat in the diet and bodily levels of nitric oxide, a naturally occurring signalling molecule that is related to inflammation and cancer development.

Nitric oxide (NO) is one of the critical components of the vasculature, regulating key signalling pathways in health. In macrovessels, NO functions to suppress cell inflammation as well as adhesion. In this way, it inhibits thrombosis and promotes blood flow. It also functions to limit vessel constriction and vessel wall remodelling. In microvessels and particularly capillaries, NO, along with growth factors, is important in promoting new vessel formation, a process termed angiogenesis. With age and cardiovascular disease, animal and human studies confirm that NO is dysregulated at multiple levels including decreased production, decreased tissue half-life, and decreased potency.

“We are trying to understand how subtle changes in the tumour microenvironment affect cancer progression at the molecular level. Cancer is a very complicated disease,” said Anuj Yadav, a senior research associate and the study’s lead coauthor.

Cancer is more than just a few tumour cells, rather the entire microenvironment of the tumour supporting the cells, Yadav explained.

“Inflammation can play a significant role in this environment. Certain inflammatory response comes from highly processed foods, which are high in calories and high in fat. We wanted to understand the links between food, inflammation, and tumors at a molecular level, so we had to develop advanced probes to be able to visualise these changes,” he said.

Yadav and coauthors are familiar with existing research linking increased NO levels to inflammation, and inflammation to cancer. Proving the connection between high-fat diets and NO levels on a molecular level required developing a highly sensitive molecular probe capable of deep-tissue imaging.

The team designed a molecular probe which is the first of its kind to be used in bioluminescence imaging of NO in cancer.

“Our group specialises in making designer molecules, which allows us to look at molecular features that are invisible to the naked eye,” said Jefferson Chan, an associate professor of chemistry at the University of Illinois Urbana-Champaign and the study’s principal investigator. “We design these custom-made molecules to discover things that weren’t previously known.”

With the probe, the researchers compared the tumourigenicity of the breast-cancer-carrying mice on a high-fat diet (60% of calories coming from fat) with mice on a low-fat diet (10% of calories coming from fat) by measuring the NO levels in both groups.

“As a result of the high-fat diet, we saw an increase in nitric oxide in the tumor microenvironment,” said Michael Lee, a student researcher in the Chan lab and a lead coauthor on this study. “The implication of this is that the tumor microenvironment is a very complex system, and we really need to understand it to understand how cancer progression works. A lot of factors can go into this from diet to exercise – external factors that we don’t really take into account that we should when we consider cancer treatments.”

The authors emphasised the importance of proving a direct link between a high-fat diet, NO levels, and cancer development. With this association now known, new implications exist for cancer diagnosis and treatment.

“Without this technology, you wouldn’t see this missing molecular link,” said Chan. “Now that we know that this is happening, how do we prevent it, and how do we improve the situation?”

Source: Beckman Institute