Overeating impairs brain insulin function, can lead to diabetes and obesity

New research from Mount Sinai School of Medicine sheds light on how overeating can cause a malfunction in brain insulin signaling, and lead to obesity and diabetes. Christoph Buettner, MD, PhD, Associate Professor of Medicine (Endocrinology, Diabetes and Bone Disease) and his research team found that overeating impairs the ability of brain insulin to suppress the breakdown of fat in adipose tissue.

In previous research Dr. Buettner's team established that brain insulin is what suppresses lipolysis, a process during which triglycerides in fat tissue are broken down and fatty acids are released. When lipolysis is unrestrained, fatty acid levels are elevated, which can initiate and worsen obesity and type 2 diabetes. The current study is published online in The Journal of Biological Chemistry. The first study was published in the February 2, 2011 issue of Cell Metabolism.

"We are interested in understanding why people who eat too much eventually develop diabetes. Our recent studies suggest that once you overeat, your brain develops insulin resistance. Since brain insulin controls lipolysis in adipose tissue by reducing sympathetic nervous system outflow to adipose tissue, brain insulin resistance causes increased spillage of fatty acids from adipose tissue into the blood stream," said Dr. Buettner.

Increased fatty acids induce inflammation and that, in turn, can further worsen insulin resistance, which is the core defect in type 2 diabetes. Fatty acids also increase glucose production in the liver which raises blood glucose levels, Dr. Buettner explained. "It's a vicious cycle and while we knew that this can begin with overeating, this study shows that it is really the brain that is harmed first which then starts the downward spiral."

In this study, researchers fed rats a high-fat diet comprised of 10 percent lard for three consecutive days. This increased their daily caloric intake by up to 50 percent compared to the control rats that were fed a regular low fat diet. The researchers then infused a tiny amount of insulin into the brains of both groups of rats that they had shown in earlier studies to suppress release of glucose from the liver and fatty acids from fat tissue. They found that overeating impaired the ability of brain insulin to suppress glucose release from the liver and lipolysis in fat tissue. Similarly, short-term overeating in humans is known to produce comparable insulin resistance which could be explained by brain insulin resistance.

"When you overeat, your brain becomes unresponsive to these important clues such as insulin, which puts you on the road to diabetes. We believe that what happens in rats also happens in humans" said Dr. Buettner.

Dr. Buettner's team plans to investigate methods of improving brain insulin function that could restrain lipolysis and improve insulin resistance.

Plant-Based Diets Can Remedy Chronic Diseases

According to the World Health Organization (WHO), 63 percent of the deaths that occurred in 2008 were attributed to non-communicable chronic diseases such as cardiovascular disease, certain cancers, Type 2 diabetes and obesity—for which poor diets are contributing factors. Yet people that live in societies that eat healthy, plant-based diets rarely fall victim to these ailments. Research studies have long indicated that a high consumption of plant foods is associated with lower incidents of chronic disease. In an article entitled The Chronic Disease Food Remedy in the October issue of Food Technology magazine, Senior Writer/Editor Toni Tarver discusses recent discoveries in nutritional genomics that explain how plant-based diets are effective at warding off disease.

The article indicates that bioactive compounds in plant foods play a role in controlling genetic and other biological factors that lead to chronic disease. For example, antioxidants in plant foods counter free radicals that can cause chronic inflammation and damage cells. And other plant compounds help control a gene linked to cardiovascular disease and plaque buildup in arteries and the genes and other cellular components responsible for forming and sustaining tumors.

William W. Li, M.D., President and Medical Director of the Angiogenesis Foundation in Cambridge, Mass., says that all consumers should look at their diets as if food is the medicine necessary to maintain healthy, disease-free lives. “Prevention is always better than a cure,” said Li. Foods that may help prevent cancer and other chronic diseases include artichokes, black pepper, cinnamon, garlic, lentils, olives, pumpkin, rosemary, thyme, watercress, and more. For a more comprehensive list of medicinal foods, read “The Chronic Disease Food Remedy” in the October 2012 issue of Food Technology.

No Benefit from Routine Health Checks

Carrying out general health checks does not reduce deaths overall or from serious diseases like cancer and heart disease, according to Cochrane researchers. The researchers, who carried out a systematic review on the subject for The Cochrane Library, warn against offering general health checks as part of a public health programme.

In some countries, general health checks are offered as part of standard practice. General health checks are intended to reduce deaths and ill health by enabling early detection and treatment of disease. However, there are potential negative implications, for example diagnosis and treatment of conditions that might never have led to any symptoms of disease or shortened life.

The researchers based their findings on 14 trials involving 182,880 people. All trials divided participants into at least two groups: one where participants were invited to general health checks and another where they were not. The number of new diagnoses was generally poorly studied, but in one trial, health checks led to more diagnoses of all kinds. In another trial, people in the group invited to general health checks were more likely to be diagnosed with high blood pressure or high cholesterol, as might be expected. In three trials, large numbers of abnormalities were identified in the screened groups.

However, based on nine trials with a total of 11,940 deaths, the researchers found no difference between the number of deaths in the two groups in the long term, either overall or specifically due to cancer or heart disease. Other outcomes were poorly studied, but suggested that offering general health checks has no impact on hospital admissions, disability, worry, specialist referrals, additional visits to doctors or time off work.

"From the evidence we've seen, inviting patients to general health checks is unlikely to be beneficial," said lead researcher Lasse Krogsbøll of The Nordic Cochrane Centre in Copenhagen, Denmark. "One reason for this might be that doctors identify additional problems and take action when they see patients for other reasons."

"What we're not saying is that doctors should stop carrying out tests or offering treatment when they suspect there may be a problem. But we do think that public healthcare initiatives that are systematically offering general health checks should be resisted."

According to the review, new studies should be focused on the individual components of health checks and better targeting of conditions such as kidney disease and diabetes. They should be designed to further explore the harmful effects of general health checks, which are often ignored, producing misleading conclusions about the balance of benefits and harm. Another problem is that those people who attend health checks when invited may be different to those who do not. People who are at a high risk of serious illness may be less likely to attend.

Cranberry Juice Unlikely to Prevent Cystitis

Cranberry juice is unlikely to prevent bladder and kidney infections, according to an updated systematic review published in The Cochrane Library. The authors analysed the most up-to-date evidence and concluded that any benefit, if present at all, is likely to be small and only for women with recurrent UTI.

Urinary tract infections (UTIs) affect the bladder, as in cystitis, and sometimes the kidneys. Cranberries and cranberry juice have been used to prevent UTIs for decades, although it is not clear how they might help protect against infection. According to one theory, certain sugars and flavanol compounds in cranberries prevent bacteria sticking to cells lining the walls of the urinary tract. Several systematic reviews have been published on the subject in The Cochrane Library, each time incorporating more evidence. In the last review in 2008, it was concluded that cranberries offer a small benefit in preventing recurring UTIs in women.

In the current review, the researchers gathered together evidence from 24 studies that involved a total of 4,473 people. These studies included 14 added since the 2008 update. Those in treatment groups were given cranberry juice, tablets or capsules, while those in control groups were given placebo cranberry products, water, methenamine hippurate, antibiotics, lactobacillus or nothing. Although in some studies there were small benefits for women suffering from recurring infections, women would have to consume two glasses of cranberry juice per day for long periods to prevent one infection. The researchers conclude that current evidence does not support cranberry juice as a means of preventing UTIs.

"Now that we've updated our review with more studies, the results suggest that cranberry juice is even less effective at preventing UTIs than was shown in the last update," said lead researcher Ruth Jepson of the University of Stirling in Stirling, UK. In the studies where participants were given juice, there were large numbers of drop-outs, suggesting it might not be acceptable to drink over long time periods. A common problem with the studies evaluating cranberry tablets or capsules was that they rarely reported the amount of active ingredient, so it was unclear whether levels would have been high enough to have any effect.

"We can't see a particular need for more studies of the effect of cranberry juice, as the majority of existing studies indicate that the benefit is small at best, and the studies have high drop-out rates," said Jepson. "More studies of other cranberry products such as tablets and capsules may be justified, but only for women with recurrent UTIs, and only if these products contain the recommended amount of active ingredient."

Eating lots of carbs, sugar may raise risk of cognitive impairment

People 70 and older who eat food high in carbohydrates have nearly four times the risk of developing mild cognitive impairment, and the danger also rises with a diet heavy in sugar, Mayo Clinic researchers have found. Those who consume a lot of protein and fat relative to carbohydrates are less likely to become cognitively impaired, the study found. The findings are published in the Journal of Alzheimer's Disease.

The research highlights the importance of a well-rounded diet, says lead author Rosebud Roberts, M.B., Ch.B., a Mayo Clinic epidemiologist.

"We think it's important that you eat a healthy balance of protein, carbohydrates and fat, because each of these nutrients has an important role in the body," Dr. Roberts says.

Researchers tracked 1,230 people ages 70 to 89 who provided information on what they ate during the previous year. At that time, their cognitive function was evaluated by an expert panel of physicians, nurses and neuropsychologists. Of those participants, only the roughly 940 who showed no signs of cognitive impairment were asked to return for follow-up evaluations of their cognitive function. About four years into the study, 200 of those 940 were beginning to show mild cognitive impairment, problems with memory, language, thinking and judgment that are greater than normal age-related changes.

Those who reported the highest carbohydrate intake at the beginning of the study were 1.9 times likelier to develop mild cognitive impairment than those with the lowest intake of carbohydrates. Participants with the highest sugar intake were 1.5 times likelier to experience mild cognitive impairment than those with the lowest levels.

But those whose diets were highest in fat -- compared to the lowest -- were 42 percent less likely to face cognitive impairment, and those who had the highest intake of protein had a reduced risk of 21 percent.

When total fat and protein intake were taken into account, people with the highest carbohydrate intake were 3.6 times likelier to develop mild cognitive impairment.

"A high carbohydrate intake could be bad for you because carbohydrates impact your glucose and insulin metabolism," Dr. Roberts says. "Sugar fuels the brain -- so moderate intake is good. However, high levels of sugar may actually prevent the brain from using the sugar -- similar to what we see with type 2 diabetes."

Sitting for protracted periods increases risk of diabetes, heart disease and death

Sitting around compromises health of people- even if they meet typical physical activity guidelines

A new study led by the University of Leicester, in association with colleagues at Loughborough University, has discovered that sitting for long periods increases your risk of diabetes, heart disease and death.

The study, which combined the results of 18 studies and included a total of 794,577 participants, was led by Dr. Emma Wilmot, a research fellow in the Diabetes Research Group at the University of Leicester. It was done in collaboration with colleagues from the newly established National Institute for Health Research (NIHR) Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit and was published in Diabetologia, the journal of the European Association of the Study of Diabetes.

According to the study, those who sit for long periods have a two fold increase in their risk of diabetes, heart disease and death. Importantly, associations were independent of the amount of moderate-to-vigorous physical activity undertaken, suggesting that even if an individual meets typical physical activity guidelines, their health may still be compromised if they sit for long periods of time throughout the day.

Dr Wilmot, a Clinical Research Fellow in Diabetes and Endocrinology based at the Leicester Diabetes Centre, Leicester General Hospital, said: "The average adult spends 50-70% of their time sitting so the findings of this study have far reaching implications. By simply limiting the time that we spend sitting, we may be able to reduce our risk of diabetes, heart disease and death".

"Our study also showed that the most consistent associations were between sitting and diabetes. This is an important message because people with risk factors for diabetes, such as the obese, those of South Asian ethnic origin, or those with a family history of diabetes, may be able to help reduce their future risk of diabetes by limiting the time spent sitting. "

Professor Stuart Biddle, of Loughborough University, and a co-investigator on the study, said: "There are many ways we can reduce our sitting time, such as breaking up long periods at the computer at work by placing our laptop on a filing cabinet. We can have standing meetings, we can walk during the lunch break, and we can look to reduce TV viewing in the evenings by seeking out less sedentary behaviours."

Professor Melanie Davies, Professor of Diabetes Medicine at the University of Leicester and honorary consultant at University Hospitals of Leicester is a co-investigator and Director of the NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit. She said:

"This paper has a very important message for the public but also for health care professionals - namely that being sedentary is common and dangerous for our long term health, particularly for diabetes and cardiovascular disease, and that this link appears to be over and above other lifestyle factors such as our diet and physical activity."

Expanding waistlines may contribute to cancer

Fat progenitor cells may contribute to cancer growth by fortifying the vessels that provide needed blood to tumors, according to preclinical research findings by investigators at The University of Texas Health Science Center at Houston (UTHealth).

The results were reported in Cancer Research, a journal of the American Association for Cancer Research.

Studies of groups of people have demonstrated a link between obesity and certain cancers; however, the physiological causes have not been identified. The World Health Organization reports that in 2008 there were more than 1.4 billion obese adults in the world and that cancer claimed the lives of 7.6 million that year.

Some researchers have theorized that what obese people eat may affect cancer progression. However, although diet is an important factor, the direct effect of excess fat tissue on tumors has to be taken into consideration, said Mikhail Kolonin, Ph.D., senior author and associate professor at the Center for Stem Cell and Regenerative Medicine at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth.

The UTHealth scientists found a new link between tumor growth and obesity. They report that tumors emit a signal that attracts progenitor cells from white adipose tissue in mouse models of cancer. These cells in turn support the network of blood vessels that nourish tumors - a process called tumor angiogenesis.

“For the first time, we have demonstrated that excess fat is a key factor in cancer progression regardless of the diet contributing to the extra weight,” Kolonin said.

“In an attempt to understand how fat tissue fuels tumor growth, our laboratory has focused on a possible role of adipose stromal progenitor cells. These cells serve as stem cells in fat tissue. We have discovered that they expand in obesity and are mobilized into the systemic circulation,” Kolonin said.

“Our experiments show that fat progenitors are recruited by tumors, where they incorporate into blood vessels and become fat cells,” said Yan Zhang, M.D., Ph.D., the study’s lead author and research scientist at the UTHealth Medical School. “We found that obese animal fat progenitor cells recruited by tumors improved vascular function and, therefore, increased survival and proliferation of cancer cells.”

Chieh Tseng, study author and graduate research assistant at the The University of Texas Graduate School of Biomedical Sciences at Houston, said, “Our work has the potential to help a lot of people. Currently, we are investigating the molecular mechanisms of fat progenitor cell homing to tumor. We are also screening for new molecules targeting the pathways through which cells traffic from fat tissue to promote tumor growth.”

“The next step in this research would be to inactivate fat progenitor cells in an effort to slow cancer progression,” said Kolonin, who is on the faculty of the graduate school and is the holder of the Jerold B. Katz Distinguished Professorship in Stem Cell Research at UTHealth.

Other UTHealth study authors include Alexes Daquinag, Ph.D., Felipe Amaya-Manzanares and Olga Sirin, Ph.D.

The study, which is titled “Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Populations of Pericytes and Adipocytes in Tumor Microenvironment,” was supported by the Cancer Prevention & Research Institute of Texas and the American Cancer Society.