Obesity triggers neurodegeneration by inducing brain insulin resistance
In a pivotal study conducted by Mroj Alassaf and colleagues at the Fred Hutchinson Cancer Research Center in the United States, a novel connection between obesity and the onset of neurodegenerative diseases, such as Alzheimer’s, has been uncovered.
The research, employing the biological model of the common fruit fly, indicates that diets high in sugar, which are commonly associated with obesity, lead to insulin resistance within the brain. This resistance hampers the brain’s capacity to eliminate cellular waste, which in turn elevates the risk of neurodegenerative conditions.
The findings, released on November 7 in the open-access publication PLOS Biology, promise to be influential in the development of medical interventions aimed at mitigating the chances of neurodegenerative disease onset.
While the correlation between obesity and neurodegenerative diseases like Alzheimer’s and Parkinson’s has been acknowledged in scientific circles, the causal mechanisms at play have eluded researchers until now.
The team’s research delved into this conundrum by leveraging the genetic and physiological parallels between fruit flies and humans. Building on prior knowledge that a diet rich in sugar instigates insulin resistance in the peripheral tissues of fruit flies, the focus now shifted to their neural tissues. The study zoomed in on glial cells, as abnormalities in microglia are recognised contributors to neuronal decay.
The study measured the protein PI3k—a biomarker for insulin sensitivity in cells. The high-sugar diet was found to diminish PI3k levels in glial cells, suggesting a state of insulin resistance. The team also examined the fruit fly’s version of microglia, known as ensheathing glia, responsible for clearing out neuronal waste, including deteriorating axons.
These glial cells exhibited depleted levels of Draper, a protein integral to their waste-removal function, indicating a compromised ability. Subsequent experiments demonstrated that artificially reducing PI3k levels not only caused insulin resistance but also led to decreased Draper levels in the ensheathing glia. Moreover, when the team inflicted damage on olfactory neurons, the ensheathing glia of sugar-fed flies failed to clear the resulting neuronal debris due to their unresponsive Draper levels.
The researchers conclude by stating that their work with fruit flies has established that high-sugar diets induce insulin resistance in glial cells, which disrupts their neuronal cleanup role. This study sheds light on the potential pathways through which diets leading to obesity may elevate the risk of neurodegenerative diseases.
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Rising obesity levels may intensify menopause symptoms and reduce hormone therapy efficiency, preliminary study indicates
The global surge in obesity, with an estimated 13% of adults now grappling with the condition, is a growing concern. A recent report suggests that obesity prevalence is higher among women than men (15% vs. 11%), with a more pronounced incidence in developed nations. Particularly in the United States, data from the Centers for Disease Control and Prevention (CDC) reveals that in 2020, 41.9% of individuals aged 20 and over were categorised as having obesity.
The far-reaching health implications of obesity are well-documented, encompassing a higher propensity for heart attacks, strokes, type 2 diabetes, respiratory ailments, and musculoskeletal issues.
A nascent study unveils a potential additional concern: obesity might amplify the severity of menopausal symptoms and compromise the effectiveness of hormone therapy aimed at alleviating these symptoms. The study’s lead author, Dr. Anita Pershad from the Eastern Virginia Medical School, shared her insights stating, “The core inference from our study is that obesity might exacerbate a woman’s menopausal symptoms while concurrently diminishing the relief provided by hormone therapy (HT).”
However, Dr. Kara McElligot, a NAMS-certified menopause practitioner and medical advisor at Mira, underscored the preliminary nature of this investigation, which encompassed a mere 119 participants and was executed retrospectively via chart review, thus inheriting a higher risk of bias.
The research, though yet to be peer-reviewed, was showcased at the 2023 Annual Meeting of The Menopause Society in Philadelphia, held between September 27 and 30. The study, spanning five years, meticulously reviewed the medical records of 119 women visiting a menopause clinic. These women were segregated into two cohorts based on their Body Mass Index (BMI)—those with a BMI above 30 were categorised as having obesity, while those below this threshold formed the other group.
The evaluation revealed no substantial disparity between the groups concerning age, the extent of menopause, hormone therapy utilisation, and acceptance. However, a significant finding emerged: women with obesity exhibited a higher propensity to report symptoms such as vasomotor symptoms (hot flashes), genitourinary/vulvovaginal symptoms, mood fluctuations, and diminished libido.
Dr. Sherry Ross, a seasoned OB/GYN at Providence Saint John’s Health Center in Santa Monica, elucidated a plausible cause, positing that women with obesity might experience intensified hot flashes and night sweats as fatty tissues could act as insulators, retaining heat within the body. Another theory proposes that obesity might trigger hormonal imbalances, thus engendering elevated oestrogen levels which, in turn, could exacerbate menopausal symptoms.
Dr. Ashley Parr, D.O., OB/GYN at The Women’s Hospital at MemorialCare Saddleback Medical Center, concurred with this notion, adding that the oestrogen-producing capability of fat cells could potentially alter the hormonal equilibrium of women with obesity during menopause, even post the cessation of ovarian function.
Moreover, the research identified a diminished likelihood of symptomatic relief post systemic and/or localised hormone therapy among women with obesity, compared to their counterparts without obesity. Dr. Pershad disclosed ongoing inquiries into the ambiguous efficacy of hormone therapy among women with obesity.
She further discussed exploring alternative designs and administration routes to potentially enhance hormone therapy effectiveness. Concurrently, Dr. Parr highlighted that obesity-associated risks for other health conditions like heart disease and breast cancer could deter the choice of hormone replacement, prompting considerations for non-hormonal treatment alternatives such as SSRIs, SNRIs, and vaginal oestrogen based on the specific symptoms sought to be addressed.
Dr. McElligot delineated the conceivable reasons behind the diminished effectiveness of hormone therapy in women with obesity, referring to various factors influencing the severity and experience of oestrogen deficiency, with obesity being a prime contender. She also brought attention to liver drug metabolism studies that reveal variations in circulating drug quantities based on BMI among adults, shedding light on the possible need for revising hormone therapy dosing recommendations to cater to the distinct metabolic dynamics presented by obesity.
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Revitalising weight loss: The miraculous power of “beige fat” in reversing age-related weight gain
Discovering the ability to activate the body’s own fat-burning mechanisms and counteract age-related metabolic changes might seem like an unattainable dream, but researchers at Cornell University’s Division of Nutritional Sciences are working towards making it a reality. Their recent study explores the potential of a specific type of fat cells known as “beige fat” to reverse the effects of a slowing metabolism.
In mammals, including humans, two main types of fat exist: white adipose tissue (WAT), which stores excess calories, and brown adipose tissue (BAT), which burns calories to generate heat and regulate body temperature. The study sheds light on the therapeutic possibilities of a third type of fat called beige fat, a subtype of WAT. Beige fat shares characteristics with both white and brown fat, possessing thermogenic properties similar to brown fat and the ability to regulate blood sugar levels and reduce fatty acids associated with conditions like arterial hardening and heart disease.
The formation of beige fat occurs when adipose progenitor cells, a type of stem cell found within white fat, are stimulated by prolonged exposure to cold temperatures. However, as individuals age, their response to this stimulus weakens, leading to an imbalance favouring the production of white fat.
“Seasonal changes in beige fat occur in young humans, but an older person would have to stand outside in the snow in their underwear to achieve those same effects,” explains Dan Berry, an assistant professor in the Division of Nutritional Sciences at Cornell University.
Previous research by Berry revealed that the ageing process inhibits the formation of beige fat cells in response to cold temperatures.
The study’s lead author, Abigail Benvie, a doctoral student researcher in Berry’s lab, explains that the ultimate goal of their research is to find ways to stimulate metabolic pathways without subjecting individuals to prolonged cold exposure. Researchers successfully suppressed this pathway in ageing mice and stimulated the production of beige fat cells in areas where only white fat would typically form.
This research not only offers potential solutions for age-related weight gain and associated health conditions but also provides insights into the molecular mechanisms underlying beige fat formation. The study’s co-authors, including graduate students Derek Lee, Benjamin M. Steiner, and Siwen Xue, as well as Yuwei Jiang from the University of Illinois at Chicago, plan to further investigate the identified pathway and explore other molecular regulators of beige fat formation. With a $2.2 million, five-year grant from the National Institutes of Health, Berry’s lab aims to deepen our understanding of how these regulators change in levels and activity during the ageing process.
The study, published in the journal Nature Communications, represents a significant step forward in harnessing the potential of beige fat to combat age-related weight gain and improve metabolic health.
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Obesity associated with diminished bone strength, particularly in men
Despite the protective implication often associated with high body weight in terms of fracture risk, recent studies suggest that obesity may in fact raise the risk of fractures, particularly in men with high body fat content.
A comprehensive examination of dual x-ray absorptiometry (DXA) data from a broad spectrum of over 10,000 U.S. individuals revealed an intricate connection between body weight and bone density. Dr. Rajesh Jain and Dr. Tamara Vokes, both from the University of Chicago, discussed these complex findings in the Journal of Clinical Endocrinology & Metabolism.
The duo discovered that each 1 kg/m2 increase in lean mass index correlated with a 0.19 higher T-score in people below 60 years of age. However, every corresponding increase in fat mass index was associated with a 0.10 decline in T-score, with a significant statistical difference (P<0.001).
Their research indicated that while lean mass positively impacted bone mineral density (BMD) equivalently in both genders, the deleterious effect of fat mass was more pronounced in men, leading to a 0.13 lower T-score per additional 1 kg/m2, compared to a 0.08 drop in women (P<0.001 for interaction).
“Our analysis of a large, heterogeneous population presenting a wide range of BMI indicated a clear negative correlation between bone density and fat mass, and a positive correlation with lean mass,” Jain and Vokes stated.
The researchers highlighted that despite lean mass exhibiting a stronger overall impact than fat mass, the detrimental effects of fat on BMD were significantly more evident in men and individuals with excessive fat content.
These insights hold critical clinical implications as they suggest obesity could contribute to declining BMD in patients traditionally not perceived as high fracture risk, and who therefore might not typically undergo DXA screening.
Contrasting previous studies constrained by small sample sizes or referral bias, Jain and Vokes’ findings reflect broader U.S. population data. They emphasise that obesity does not provide immunity against low BMD, advocating for clinicians to assess bone density, especially when other risk factors are present.
To reach their conclusions, the researchers assessed data from the National Health and Nutrition Examination Surveys conducted from 2011 to 2018. This dataset encompassed body composition and DXA measurements for 10,814 individuals aged 20 to 59.
Using linear regression models with total body BMD as the dependent variable, the researchers scrutinised the impact of lean and fat mass, accounting for age, gender, race/ethnicity, height, and smoking status. Notably, they highlighted the challenge of disentangling the interconnected influences of fat and lean mass on bone density.
Prior studies exploring the impact of fat mass on bone density reported varying results due to differing statistical methods and are somewhat outdated, the researchers pointed out. Moreover, the current study benefited from a densitometer with a higher weight limit, allowing for the examination of more severe obesity cases.
However, the study had limitations, including its focus on adults below 60 years, leaving room for potentially different body composition and bone mass relationships in older individuals. It also didn’t evaluate factors besides sex hormones that might elucidate the observed gender differences in the link between fat mass and bone density.
Despite women generally having a higher proportion of body fat, fat accumulation patterns differ by gender, with women typically storing fat in the hip and thigh areas, and men in the trunk and abdomen. Jain and Vokes acknowledged that differences in fat distribution might influence BMD, although their study could not conclusively prove this.
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Obesity in childhood and puberty linked to higher risk of blood clots in later life
According to a new study by the University of Gothenburg, being overweight during childhood and early adulthood increases the risk of developing blood clots in later years. The study analysed the health data of 37,000 men and their early body mass index (BMI) and any blood clots that developed as they got older. The researchers found that both overweight in childhood and overweight in young adulthood increased the risk of venous blood clots later in life, with overweight in young adulthood proving to be a more influential factor than childhood overweight. While most blood clots occur in the legs and are not dangerous, they can become life-threatening if they travel to the lungs and cause a pulmonary embolism.
The link between obesity and blood clots is already well known, but the impact of a higher BMI in childhood on the risk was unclear. The researchers examined the data of a large group of men in Sweden who were born between 1945 and 1961, looking at school records at age 8 and Armed Forces medical examinations at age 20 to establish BMI data. They then looked at blood clot data on the men up to an average age of 62.
The study found that BMI at both age 8 and age 20 can be linked to blood clots independently of each other. As adults, the researchers found that two groups were more at risk – those who had been overweight both as a child and in early adulthood, and those with a normal weight in childhood but who became overweight in early adulthood. In addition, the study found that carrying excess weight in both childhood and early adulthood increased a person’s risk of arterial thrombi, which are clots that result from constricted blood vessels with fatty deposits. However, the researchers noted that more research is needed in this area as they only found a small number of cases.
The study’s senior authors emphasised that obesity and overweight during puberty seem to have a marked impact on a person’s future risks of venous thrombi. The study has been published in the Journal of Internal Medicine.
Obesity can lead to frailty in old age, study finds
A new study has found that adults with obesity are at greater risk of experiencing frailty in later life than adults with an average body mass index (BMI).
Researchers conducted a long-term study on adult men and women in Norway and discovered that obesity puts individuals at risk of becoming frail as they age. Frailty is characterised by physical deterioration and increased vulnerability, and while it has been associated with underweight older adults, the study reveals a positive association between obesity and the risk of frailty among older adults.
The study, published in the BMJ Open journal, analysed the body mass index and waist circumference of 2,340 women and 2,169 men over the age of 45 between 1994 and 1995. The participants were followed up for a period of 21 years to determine their risk of frailty. The researchers defined physical frailty as having three or more symptoms including poor grip strength, slow walking speed, exhaustion, unintentional weight loss, and low physical activity.
The findings show that participants with “baseline obesity” were more likely to be frail or pre-frail compared to those with an average BMI. Additionally, those with high waist circumference throughout follow-up were also more likely to be pre-frail or frail compared to participants with a stable normal waist circumference trajectory. Excess weight exacerbating the decline in muscle strength and physical capacity that occurs with age, along with metabolic disorders, inflammaging, and oxidative stress associated with obesity, could contribute to the risk of frailty.
The study’s lead author, Dr. Anju Jain, emphasised the importance of early intervention to prevent and treat obesity. She noted that while weight loss can be challenging, it is possible and can have significant health benefits. She also called for more public health efforts to promote healthy eating and physical activity throughout life.
The researchers caution against viewing frailty as solely a wasting disorder and highlight the importance of routinely assessing and maintaining optimal BMI and waist circumference throughout adulthood to reduce the risk of frailty in later life.
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Excess weight, obesity more deadly than previously believed
A new study from the University of Colorado Boulder, and published in the journal Population Studies, has found that the risk of death from excess weight or obesity is much higher than previously believed, with mortality rates increased by between 22% to 91%.
The research challenges the “obesity paradox,” which suggests that only extremely high levels of excess weight are associated with increased mortality risk. The study analysed data from nearly 18,000 people and found that using body mass index (BMI) to study health outcomes can bias findings, potentially leading to underestimates of the consequences of living in an environment where unhealthy food is cheap and sedentary lifestyles are the norm. The study estimates that about one in six U.S. deaths are related to excess weight or obesity.
The research found that a full 20% of people classified as having a “healthy” weight had previously been in the overweight or having obesity category, and that these individuals had a substantially worse health profile than those in the “healthy” category whose weight had been stable. The study also found that the health and mortality consequences of high BMI are duration-dependent, meaning that people who have spent most of their lives at a low BMI but have recently gained weight may have better health profiles than those who have had overweight or obesity for most of their lives.
The study’s author, Ryan Masters, hopes that the research will alert scientists to be “extremely cautious” when making conclusions based on BMI, and will draw attention to the public health crisis of an “obesogenic” environment in the U.S. Masters noted that the prospects of healthy ageing into older adulthood do not look good for groups born in the 1970s or 1980s who have lived their whole lives in this obesogenic environment. The study estimates that about 16% of U.S. deaths are related to excess weight or obesity, a figure that is eight times higher than previous research had suggested.
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Scientists find link between obesity and dementia
According to a new study published in the journal Alzhiemers & Dementia journal , obesity could be a major factor in the development of dementia. Researchers found that having overweight or obesity in mid-life could increase the risk of developing Alzheimer’s disease and other forms of dementia later in life.
The study analysed data from over 1.3 million adults in the United States, Europe, and Asia. It found that people who had overweight or obesity in mid-life had a 31% higher risk of developing dementia than those who were of a normal weight. The risk increased to 82% for those who had severe obesity.
The researchers also found that having type 2 diabetes further increased the risk of developing dementia in individuals with overweight or obesity. This is because obesity and diabetes are both associated with inflammation, insulin resistance, and other metabolic abnormalities that can damage the brain and increase the risk of dementia.
The study’s lead author, Dr. Elina Hyppönen, emphasised that the findings highlight the importance of maintaining a healthy weight throughout life to reduce the risk of dementia. She suggested that lifestyle interventions, such as exercise and a healthy diet, could help prevent obesity and diabetes and lower the risk of dementia.
The study’s findings add to the growing body of evidence linking obesity and dementia. Previous research has suggested that obesity can increase the risk of cognitive decline and reduce brain volume, particularly in the hippocampus, which is critical for memory and learning.
The World Health Organization estimates that around 50 million people worldwide have dementia, and that number is expected to triple by 2050. The study’s authors suggest that preventing obesity and diabetes could be an important strategy for reducing the global burden of dementia.
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Obesity in your 50s ‘gives you the same health problems as a 75-year-old’, study shows
Having obesity can cause you to age prematurely, with 55-year-olds who are significantly overweight expected to experience the same health problems as 75-year-olds without obesity.
Researchers in Finland and the UK carried out a study on the likelihood of multiple morbidity, whereby individuals are at risk of experiencing several health conditions at the same time, based on their age and weight. The research found that individuals with obesity are five times more likely to suffer from simple multi-morbidity and over 12 times more likely to suffer from complex multi-morbidity compared to individuals with healthy weights. The study used a group of 115,000 Finns and found that just under 20% of people with healthy weights had two health problems by the age of 75. In contrast, among those with obesity, the same proportion was reached by 55 years old. A separate study of 500,000 Britons showed similar results.
According to the study, obesity advances the age at which individuals are likely to experience health problems. While health problems such as heart disease, type 2 diabetes, and cancer are already known to be more likely among individuals with obesity, this study is the first to provide a quantification of how obesity can cause health problems to emerge earlier. The study found that the impact of obesity on mortality is not as significant, meaning that those who are severely overweight are more likely to suffer from health problems for many years than to die decades earlier.
The Lancet Diabetes & Endocrinology medical journal has published a warning by two Israeli medics about the implications of increasing numbers of older people with obesity, who may be subject to more drug side effects and interactions, adverse events, complications, hospital admissions, and disabilities. Unemployment and welfare dependency may also rise as a result.
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