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Why a high fat diet could reduce the brain’s ability to regulate food intake

Calorie intake is regulated in the short-term by cells called astrocytes (large star-shaped cells in the brain that regulate many different functions of neurons in the brain) that control the signalling pathway between the brain and the gut. Continuously eating a high fat/calorie diet seems to disrupt this signalling pathway.

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Regularly eating a high fat/calorie diet could reduce the brain’s ability to regulate calorie intake. New research in rats published in The Journal of Physiology found that after short periods of being fed a high fat/high calorie diet, the brain adapts to react to what is being ingested and reduces the amount of food eaten to balance calorie intake. The researchers from Penn State College of Medicine, US, suggest that calorie intake is regulated in the short-term by cells called astrocytes (large star-shaped cells in the brain that regulate many different functions of neurons in the brain) that control the signalling pathway between the brain and the gut. Continuously eating a high fat/calorie diet seems to disrupt this signalling pathway.

Understanding the brain’s role and the complex mechanisms that lead to overeating, a behaviour that can lead to weight gain and obesity, could help develop therapies to treat it. Obesity is a global public-health concern because it is associated with increased risk of cardiovascular diseases and type 2 diabetes. In England, 63% of adults are considered above a healthy weight and around half of these are living with obesity. One in three children leaving primary school are overweight or obese1.

Dr Kirsteen Browning, Penn State College of Medicine, US, 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. Their activation triggers the release of gliotransmitters, chemicals (including glutamate and ATP) that excite nerve cells and enable normal signalling pathways to stimulate neurons that control how the stomach works. 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 (N=205, 133 males, 72 females) 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. Enabling the researchers to specifically inhibit astrocytes in a particular region of the brainstem (the posterior part of the brain that connects the brain to the spinal cord), so they could assess how individual neurons behaved to studying rats’ behaviour when awake.

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 Kirsteen 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.”

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All work and no play will really make a dull life – research

‘Achievement’ and ‘conformity’ values had no impact on happiness whatsoever. However, the researchers believe achievement could impact on happiness when linked to job satisfaction or the amount of days worked.

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A study across three countries led by the Department of Psychology’s Dr Paul Hanel discovered people who prioritised achievement over enjoyment were less happy on the next day. Whereas those who aimed for freedom said they had a 13% increase in well-being, recording better sleep quality and life satisfaction. And participants who tried to relax and follow their hobbies recorded an average well-being boost of 8% and a 10% drop in stress and anxiety.

Dr Hanel worked with colleagues at the University of Bath on the Journal of Personality-published study. For the first time, it explored how following various values impacts our happiness.

Dr Hanel said: “We all know the old saying ‘All work and no play makes Jack a dull boy’ and this study shows it might actually be true. There is no benefit to well-being in prioritising achievement over fun and autonomy. This research shows that there are real benefits to having a balanced life and taking time to focus on enjoying ourselves and following individual goals. Ironically by doing this, people could in fact be more successful as they will be more relaxed, happier and satisfied.”

The study –Value Fulfilment and Well-being: Clarifying Directions Over Time – examined more than 180 people in India, Turkey and the UK. They filled in a diary across nine days and recorded how following different values affected them.

Interestingly all nationalities reported the same results with the following of ‘hedonism’ and ‘self-direction’ values leading to increased happiness. ‘Achievement’ and ‘conformity’ values had no impact on happiness whatsoever. However, the researchers believe achievement could impact on happiness when linked to job satisfaction or the amount of days worked.

Professor Greg Maio, University of Bath, said: “This multination project was an exciting foray into questions about how values affect well-being in day-to-day life. People often spend most of their days working hard for their daily income, studies, and careers. Against this backdrop, where achievement-oriented values have ring-fenced a great portion of our time, we found that it helps to value freedom and other values just enough to bring in balance and recovery.”

In the future, it will be interesting to consider how this pattern interacts with relevant traits, such as conscientiousness, and situational contexts, such as type of employment, Maio added.

It is hoped the research will now influence mental health provision and influence therapeutic give to clients.

Dr Hanel added: “Our research further shows that it might be more important to focus on increasing happiness rather than reducing anxiety and stress, which is of course also important, just not as much.”

The study was published in collaboration with Hamdullah Tunç, Divija Bhasin, and Dr Lukas Litzellachner.

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Why breast cancer survivors don’t take their medication, and what can be done

For roughly 80% of breast cancer survivors, treatment doesn’t end with surgery, radiation and chemotherapy. Instead, for the next five to 10 years, doctors recommend that they take medication to block sex hormones, which can fuel tumor growth and spark recurrence.

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For roughly 80% of breast cancer survivors, treatment doesn’t end with surgery, radiation and chemotherapy. Instead, for the next five to 10 years, doctors recommend that they take medication to block sex hormones, which can fuel tumor growth and spark recurrence.

The drugs are life-saving: They’ve been shown to cut risk of cancer recurrence by as much as half in patients with hormone receptor-positive tumors (HR+)—the most common form of breast cancer. Yet despite their promised benefits, 40% of patients stop taking them early and a third take them less frequently than directed.

New CU Boulder research, published this month in the Journal of Clinical Oncology, sheds light on why that is and what doctors and the health care system can do about it.

It found that, overall, interventions can increase medication adherence by nearly 1.5 times. But some strategies work better than others.

“Our bottom-line finding is that there are strategies that do work in supporting women to take these life-extending medications, and that we as a cancer care community need to do better,” said senior author Joanna Arch, a professor in the Department of Psychology and Neuroscience and member of the CU Cancer Center on the Anschutz Medical Campus.

Arch noted these so-called “adjuvant endocrine therapies,” like the estrogen-blockers Tamoxifen and aromatase inhibitors, can be costly and come with a host of side effects, including weight gain, sexual side effects, joint pain, depression and sleeplessness.

“Imagine going from your normal estrogen activity to little or no estrogen within days. That’s what these medications do,” she said. “But the women who take them as prescribed also have lower recurrence rates and live longer. It’s a dilemma.”

As more next-generation cancer drugs, including chemotherapy agents, shift from infusions provided in a clinic to oral therapies taken at home, the medical community has grown increasingly interested in developing ways to make sure patients take their pills.

In a sweeping meta-analysis, Arch and her colleagues analyzed 25 studies representing about 368,000 women to gain insight into what works and what doesn’t. 

Educational pamphlets are not enough 

The study found that cost-cutting policy changes, such as providing generic alternatives or requiring insurance companies to cover pills at the same level as infusions, consistently worked. Such “oral parity laws” have been passed in 43 states in recent years.

In one study, participants were asked to create stickers to put on their pill boxes.

Mobile apps and texts to remind patients to take their medication and psychological/coping strategies also yielded modest improvements.

The study’s findings around managing side effects were complicated: Simply educating women on side effects, via pamphlets or verbal explanations, generally failed to increase the likelihood that women took their medication as directed.

But things such as physical therapy, exercise and behavioral counseling aimed at alleviating or managing side effects often worked.

“Education in and of itself is not enough. That is a clear finding,” said Arch, suggesting that doctors write referrals to practitioners who specialize in side effects and follow up with appointment reminders. “Most oncologists, I believe, don’t realize how low adherence is for these women. They assume that if they write the prescription, it’s being taken.”

Addressing mental health is key

One study included in the meta-analysis was Arch’s own.

In it, women were asked to identify their primary motivation for taking their medication—whether it was living to see their child or grandchild grow up, pursuing their art or running a marathon someday. Via an online program, they created a sticker with a photo representing that goal, and the words “I take this for…” below it. Then, they stuck it on their pill box.

Participants were more likely to take their pills, at least for the first month, than those who didn’t.

“Even just a tiny thing like this can help,” said Arch.

Notably, very few studies looked at whether treating depression can help. Arch, aiming to fill this gap, recently launched her own pilot trial.

“One of the most consistent predictors of not adhering to any medication is depression,” she said. “Depression taps motivation.”

The new Journal of Clinical Oncology study is the first meta-analysis to show that interventions can be helpful, and that’s important, said Arch, because insurance companies need data to make decisions about what to cover.

But the study also showed that the effects are relatively modest and that there is room for improvement.

Arch said she hopes the study will spark more research into novel ways to support survivors:

“We have a lot of work to do.”

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Children with higher BMI at increased risk of developing depression

Associations between a higher BMI and depression were weaker between ages 16 and 21 indicating ages 12-16 is a sensitive point where preventative methods could be beneficial.

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Children between ages 12 and 16 with a higher body mass index (BMI) are at an increased risk of developing depression symptoms, new research has found.

Associations between a higher BMI and depression were weaker between ages 16 and 21 indicating ages 12-16 is a sensitive point where preventative methods could be beneficial.

The study, published in Psychological Medicine by researchers from King’s College London, analysed data from more than 10,000 twins in the Twins Early Development Study (TEDS) and UK Adult Twin Registry (TwinsUK).

In the TEDS depressive symptoms, such as low mood, loneliness and exhaustion, were self-reported in twins born between 1994 and 1996. Researchers looked at the relationship between BMI and depression at ages 12, 16 and 21.

They found that children between ages 12-16 with a higher BMI were at an increased risk of developing depression than between ages 16-21. Researchers also found that there was a stronger association for children with a higher BMI at an early age to develop depression at a later age, than children with depression first to have a higher BMI later in childhood.  

First author Dr Ellen Thompson, from King’s College London, said: “Understanding the relationship between mental ill-health and weight in adolescence is vital to provide timely support where needed. This study shows a stronger association between having a higher BMI at age 12 years and subsequent depression symptoms at age 16 years than the reverse.”

Using data from TEDS, the study also shows that the covariation between BMI and depression within each age was mostly explained by environmental factors.

Dr Thompson added: “This indicates that this relationship is environmentally mediated and could be due to several factors that adolescents may experience. Our study did not ask questions around the reasons why this effect was seen, but previous research has suggested body dissatisfaction and weight related stigma from external sources could be a factor. This study identifies a crucial point where intervention might be beneficial.”

Previous research found poverty may be a risk factor, however this study adjusted for socio-economic status and found the relationship between depression symptoms and weight to be unaffected.

This means that ages 12-16 is a sensitive and potentially detrimental time for young children and preventative measures would be beneficial. Support structures and positive body image messages could be taught in PHSE to counteract depressive symptoms.    

Co-senior author Professor Thalia Eley, Professor of Developmental Behavioural Genetics from King’s College London, said: “Our findings suggest that the experience of having higher BMI is associated with later depression. This study shows that early adolescence is a critical point for developing depressive symptoms associated with weight gain. Mental ill-health and obesity are growing concerns for Britain’s young people and this study shows how both are intertwined. Working with young teens to support them to have a positive body image using strategies such as focusing on health and wellbeing rather than weight may be useful in preventing subsequent depression.”

Co-senior author Professor Claire Steves, Professor of Ageing and Health at King’s College London, added: “Using the TwinsUK cohort, which focuses on older adult twins, our study showed that the relationship between BMI and depression was much weaker in later life.  The exact reasons for these changes over the life course need further investigation.”

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