A plant-based, Mediterranean-style diet has been shown to provide the same medical benefits for treating laryngopharyngeal reflux as popular reflux medications, according to new research.
A new study finds that the Supplemental Nutrition Assistance Program (SNAP), formerly known as Food Stamps, only covers 43-60 percent of what it costs to consume a diet consistent with federal dietary guidelines for what constitutes a healthy diet. The study highlights the challenges lower-income households face in trying to eat a healthy diet.
Approximately 90 percent of adult Americans fail to reach the US Department of Health guidelines for physical activity, which could be contributing to surging obesity rates. Now, new research suggests that physical activity can change diet preferences in males, but not in females — an area that researchers say has not been thoroughly studied.
The combination of a bacterium that normally lives in the gut and a protein-rich diet promotes a more tolerant, less inflammatory gut immune system, according to new research. The findings, in mice, suggest a way to tilt the gut immune system away from inflammation, potentially spelling relief for people living with inflammatory bowel disease.
New studies reveal the gut bacteria composition of the common fruit fly has a significant effect on diet choice and reproductive success, and its influence can be carried down to the next generation — with potential implications for human health.
A high-fat diet during pregnancy alters the development of the brain and endocrine system of offspring, new research in an animal model suggests. The new study links an unhealthy diet during pregnancy to mental health disorders such as anxiety and depression in children.
Daily tomato consumption appeared to cut the development of skin cancer tumors by half in a mouse study, report investigators.
Immune cells in the brain trigger overeating and weight gain in response to diets rich in fat, according to a new study in mice led by researchers from UC San Francisco and the University of Washington Medical Center, and published online on July 5 in Cell Metabolism.
Neurons within a region at the base of the brain known as the hypothalamus, which plays a crucial role in eating, have long been a target for the development of drugs to treat obesity. But the new study suggests that brain-resident immune cells called microglia could also be targets for obesity treatments that might avoid many side effects of the obesity drugs currently in clinical use.
“Microglia are not neurons, but they account for 10 to 15 percent of the cells in the brain,” said Suneil Koliwad, MD, PhD, assistant professor of medicine at the UCSF Diabetes Center, and a co-senior author of the new study. “They represent an untapped and completely novel way to target the brain in order to potentially mitigate obesity and its health consequences.”
Microglia in the Hypothalamus are Responsible for Diet-Driven Weight Gain
A brain region called the mediobasal hypothalamus (MBH) contains key groups of neurons that regulate food intake and energy expenditure. Normally this region attempts to match the number of calories ingested in food with our need for energy to maintain a healthy weight, but previous research has shown that dietary fats can drastically throw off this balancing act.
In the new study, the researchers fed mice a fast food-like diet rich in fat for four weeks, which is known to cause microglia to expand in number and to trigger local inflammation within the MBH. Mice fed such a diet also eat more food, burn fewer calories, and gain more weight compared to mice eating a more healthy, low-fat diet.
To learn whether the multiplying microglia are a cause of overeating and obesity in these mice, rather than a result of their weight gain, Koliwad’s team at UCSF depleted the number of microglia in the MBH of mice on the fatty diet by giving them an experimental drug, called PLX5622, which is made by Plexxikon Inc., a Berkeley, California-based biotech company. The researchers found that mice treated with the drug ate 15 percent less and gained 20 percent less weight than untreated mice on the same diet.*
The University of Washington team, led by Joshua Thaler, MD, PhD, associate professor of medicine with the UW Medicine Diabetes Institute, genetically engineered mice to prevent microglia from activating inflammatory responses, and found that these mice ate 15 percent less and gained 40 percent less weight on a high fat diet, suggesting that the inflammatory capacity of microglia itself is responsible for the animals’ overeating and weight gain.
To confirm this finding, the UCSF researchers developed a strain of genetically engineered mice in which they could use a drug to activate the inflammatory response of microglia at will. They found that even in mice fed a healthy, low-fat diet, forcing microglia-induced inflammation in the hypothalamus caused mice to eat 33 percent more food and expend 12 percent less energy, leading to a four-fold (400 percent) increase in weight gain compared to untreated mice on the same healthy diet.
“From these experiments we can confidently say that the inflammatory activation of microglia is not only necessary for high-fat diets to induce obesity, but also sufficient on its own to drive the hypothalamus to alter its regulation of energy balance, leading to excess weight gain,” said Thaler, who was a co-senior author on the new paper.
Drugs Targeting Brain Inflammation Could Help Treat Obesity
It may soon be possible to learn whether eliminating microglia can thwart weight gain in humans as well. For example, another drug made by Plexxikon, called PLX3977, which is currently in clinical trials for hard-to-treat leukemias, solid tumors, and rare forms of arthritis, acts by the same biological mechanism as PLX522, the experimental drug the UCSF team used to reduce microglia numbers in the new study. It may thus be possible to see whether cancer patients in the PLX3977 trials experience beneficial effects on body weight, Koliwad said.
In their new paper, the researchers also report that high-fat diets trigger microglia to actively recruit additional immune-system cells from the bloodstream to infiltrate the MBH. Once there, the new recruits shape-shift to take on features similar to those of the brain’s own microglia, augmenting the inflammatory response and its impact on energy balance. Therefore, the authors said, it may be possible to control overeating and weight gain through multiple immunologic approaches — targeting bona fide microglia as well as targeting cells in the blood with the capacity to enter the hypothalamus and take on microglia-like functions.
The researchers next plan to further investigate how, exactly, consumption of high-fat foods leads to the activation of microglia, and whether there are ways to intervene to block these signals.
Did Microglia Evolve Ability to Help Animals Take Advantage of Rare Feasts?
Human brain imaging studies in recent years have found that, compared to lean individuals, those who are obese are more likely to have expanded populations of glial cells — the broader class of brain cells to which microglia belong — in the hypothalamus. This same sort of phenomenon, called gliosis, is commonly seen in neurodegenerative diseases, brain trauma, bleeding, infection and brain cancer, Koliwad said, leading researchers to initially conclude that dietary excess might essentially cause a form of brain injury.
But Koliwad believes that there could be a more positive explanation for the fact that microglia have evolved the ability to rapidly trigger increased appetite and weight gain in response to a high-fat diet: rich food was only rarely available during mammalian evolutionary history, and when it was available, it would be advantageous for animals to stop hunting or foraging and focus on chowing down.
“Microglial responsiveness to dietary fats makes some sense from this evolutionary perspective,” Koliwad said. “Fats are the densest form of calories that ancient humans might ever had the opportunity to consume. So, when primitive humans finally obtained a meal after a long period of fasting, microglia may have been essential in relaying the presence of this meal to those neurons that would stimulate maximal appetite.”
But in modern environments, in which high-fat food is continually available, this same adaptation can be damaging, Koliwad said. “In our modern world, when people constantly overeat rich, high-fat foods, chronic microglial activation could produce a more permanent stimulation of neural circuits that further increase high-fat food intake, leading to the development of a vicious cycle.”
Our sense of smell is key to the enjoyment of food, so it may be no surprise that in experiments at the University of California, Berkeley, obese mice who lost their sense of smell also lost weight.
What’s weird, however, is that these slimmed-down but smell-deficient mice ate the same amount of fatty food as mice that retained their sense of smell and ballooned to twice their normal weight.
In addition, mice with a boosted sense of smell — super-smellers — got even fatter on a high-fat diet than did mice with normal smell.
The findings suggest that the odor of what we eat may play an important role in how the body deals with calories. If you can’t smell your food, you may burn it rather than store it.
These results point to a key connection between the olfactory or smell system and regions of the brain that regulate metabolism, in particular the hypothalamus, though the neural circuits are still unknown.
“This paper is one of the first studies that really shows if we manipulate olfactory inputs we can actually alter how the brain perceives energy balance, and how the brain regulates energy balance,” said Céline Riera, a former UC Berkeley postdoctoral fellow now at Cedars-Sinai Medical Center in Los Angeles.
Humans who lose their sense of smell because of age, injury or diseases such as Parkinson’s often become anorexic, but the cause has been unclear because loss of pleasure in eating also leads to depression, which itself can cause loss of appetite.
The new study, published this week in the journal Cell Metabolism, implies that the loss of smell itself plays a role, and suggests possible interventions for those who have lost their smell as well as those having trouble losing weight.
“Sensory systems play a role in metabolism. Weight gain isn’t purely a measure of the calories taken in; it’s also related to how those calories are perceived,” said senior author Andrew Dillin, the Thomas and Stacey Siebel Distinguished Chair in Stem Cell Research, professor of molecular and cell biology and Howard Hughes Medical Institute Investigator. “If we can validate this in humans, perhaps we can actually make a drug that doesn’t interfere with smell but still blocks that metabolic circuitry. That would be amazing.”
Riera noted that mice as well as humans are more sensitive to smells when they are hungry than after they’ve eaten, so perhaps the lack of smell tricks the body into thinking it has already eaten. While searching for food, the body stores calories in case it’s unsuccessful. Once food is secured, the body feels free to burn it.
Zapping olfactory neurons
The researchers used gene therapy to destroy olfactory neurons in the noses of adult mice but spare stem cells, so that the animals lost their sense of smell only temporarily — for about three weeks — before the olfactory neurons regrew.
The smell-deficient mice rapidly burned calories by up-regulating their sympathetic nervous system, which is known to increase fat burning. The mice turned their beige fat cells — the subcutaneous fat storage cells that accumulate around our thighs and midriffs — into brown fat cells, which burn fatty acids to produce heat. Some turned almost all of their beige fat into brown fat, becoming lean, mean burning machines.
In these mice, white fat cells — the storage cells that cluster around our internal organs and are associated with poor health outcomes — also shrank in size.
The obese mice, which had also developed glucose intolerance — a condition that leads to diabetes — not only lost weight on a high-fat diet, but regained normal glucose tolerance.
On the negative side, the loss of smell was accompanied by a large increase in levels of the hormone noradrenaline, which is a stress response tied to the sympathetic nervous system. In humans, such a sustained rise in this hormone could lead to a heart attack.
Though it would be a drastic step to eliminate smell in humans wanting to lose weight, Dillin noted, it might be a viable alternative for the morbidly obese contemplating stomach stapling or bariatric surgery, even with the increased noradrenaline.
“For that small group of people, you could wipe out their smell for maybe six months and then let the olfactory neurons grow back, after they’ve got their metabolic program rewired,” Dillin said.
Dillin and Riera developed two different techniques to temporarily block the sense of smell in adult mice. In one, they genetically engineered mice to express a diphtheria receptor in their olfactory neurons, which reach from the nose’s odor receptors to the olfactory center in the brain. When diphtheria toxin was sprayed into their nose, the neurons died, rendering the mice smell-deficient until the stem cells regenerated them.
Separately, they also engineered a benign virus to carry the receptor into olfactory cells only via inhalation. Diphtheria toxin again knocked out their sense of smell for about three weeks.
In both cases, the smell-deficient mice ate as much of the high-fat food as did the mice that could still smell. But while the smell-deficient mice gained at most 10 percent more weight, going from 25-30 grams to 33 grams, the normal mice gained about 100 percent of their normal weight, ballooning up to 60 grams. For the former, insulin sensitivity and response to glucose — both of which are disrupted in metabolic disorders like obesity — remained normal.
Mice that were already obese lost weight after their smell was knocked out, slimming down to the size of normal mice while still eating a high-fat diet. These mice lost only fat weight, with no effect on muscle, organ or bone mass.
The UC Berkeley researchers then teamed up with colleagues in Germany who have a strain of mice that are supersmellers, with more acute olfactory nerves, and discovered that they gained more weight on a standard diet than did normal mice.
“People with eating disorders sometimes have a hard time controlling how much food they are eating and they have a lot of cravings,” Riera said. “We think olfactory neurons are very important for controlling pleasure of food and if we have a way to modulate this pathway, we might be able to block cravings in these people and help them with managing their food intake.”
The benefits of a “Mediterranean diet” (MD) are well-known when it comes to colorectal protection, but it’s hard to know specifically what elements of the diet are the healthiest.
Now a new study, presented today at the ESMO 19th World Congress on Gastrointestinal Cancer suggests loading up on fish and fruit, and cutting back on soft drinks are the three most important things.
“We found that each one of these three choices was associated with a little more than 30% reduced odds of a person having an advanced, pre-cancerous colorectal lesion, compared to people who did not eat any of the MD components. Among people who made all three healthy choices the benefit was compounded to almost 86% reduced odds,” said Naomi Fliss Isakov, PhD fromTel-Aviv Medical Center, in Tel Aviv, Israel.
Colorectal cancer (CRC) develops from intestinal polyps and has been linked to a low-fibre diet heavy on red meat, alcohol and high-calorie foods, said Fliss Isakov.
And while the Mediterranean diet has been associated with lower rates of colorectal cancer, the definition of what elements in the diet are the most beneficial, has not always been clear.
Using dietary questionnaires from 808 people who were undergoing screening or diagnostic colonoscopies, the research team was able to dig down to look at the fine details of their daily meals.
All subjects were between 40 and 70 years old, without high risk of CRC, and answered a food frequency questionnaire.
Adherence to the MD components was defined as consumption levels above the group median for fruits, vegetables and legumes, nuts and seeds, whole grains, fish and poultry and a high ratio of monounsaturated to saturated fatty acids, as well consumption below the median of red meat, alcohol, and soft drinks.
The investigators found that compared to subjects with clear colonoscopies, those who had advanced polyps reported fewer components of the Mediterranean diet (a mean of 1.9 versus 4.5 components). Yet even consumption of two to three components of the diet, compared to none, was associated with half the odds of advanced polyps.
Odds were reduced in a dose response manner with additional MD components — meaning that the more MD components people adhered, the lower their odds of having advanced colorectal polyps.
After adjusting to account for other CRC risk factors, including other dietary components, the researchers narrowed in on high fish and fruit and low soft drinks as the best combo for reduced odds of advanced colorectal polyps.
The next step will be to see whether the MD is linked to lower risk of CRC in higher risk groups, she concluded.
Commenting on the study, ESMO spokesperson Dirk Arnold, MD, PhD, from Instituto CUF de Oncologia in Lisbon, Portugal, said “this large population-based cohort-control study impressively confirms the hypothesis of an association of colorectal polyps with diets and other life-style factors. This stands in line with other very recent findings on nutritive effects, such as the potential protective effects of nut consumption and Vitamin D supplementation which have been shown earlier this year. However, it remains to be seen whether these results are associated with reduced mortality, and it is also unclear if, and when a dietary change would be beneficial. Despite this lack of information, it makes sense to consider this diet for other health-related reasons also.”