Another reason to drink wine: It could help you burn fat

 

Drinking red grape juice or wine -- in moderation -- could improve the health of overweight people by helping them burn fat better, according to a new study coauthored by an Oregon State University researcher. The findings suggest that consuming dark-colored grapes, whether eating them or drinking juice or wine, might help people better manage obesity and related metabolic disorders such as fatty liver. Neil Shay, a biochemist and molecular biologist in OSU's College of Agricultural Sciences, was part of a study team that exposed human liver and fat cells grown in the lab to extracts of four natural chemicals found in Muscadine grapes, a dark-red variety native to the southeastern United States. One of the chemicals, ellagic acid, proved particularly potent: It dramatically slowed the growth of existing fat cells and formation of new ones, and it boosted metabolism of fatty acids in liver cells. These plant chemicals are not a weight-loss miracle, cautions Shay. "We didn't find, and we didn't expect to, that these compounds would improve body weight," he said. But by boosting the burning of fat, especially in the liver, they may improve liver function in overweight people. "If we could develop a dietary strategy for reducing the harmful accumulation of fat in the liver, using common foods like grapes," Shay said, "that would be good news." The study, which Shay conducted with colleagues at the University of Florida and University of Nebraska, complements work with mice he leads at his OSU laboratory. In one 2013 trial, he and his graduate students supplemented the diets of overweight mice with extracts from Pinot noir grapes harvested from Corvallis-area vineyards. Some of the mice were fed a normal diet of "mouse chow," as Shay calls it, containing 10 percent fat. The rest were fed a diet of 60 percent fat -- the sort of unhealthy diet that would pile excess pounds on a human frame. "Our mice like that high-fat diet," said Shay, "and they overconsume it. So they're a good model for the sedentary person who eats too much snack food and doesn't get enough exercise." The grape extracts, scaled down to a mouse's nutritional needs, were about the equivalent of one and a half cups of grapes a day for a person. "The portions are reasonable," said Shay, "which makes our results more applicable to the human diet." Over a 10-week trial, the high-fat-fed mice developed fatty liver and diabetic symptoms -- "the same metabolic consequences we see in many overweight, sedentary people," Shay said. But the chubby mice that got the extracts accumulated less fat in their livers, and they had lower blood sugar, than those that consumed the high-fat diet alone. Ellagic acid proved to be a powerhouse in this experiment, too, lowering the high-fat-fed mice's blood sugar to nearly the levels of the lean, normally fed mice. When Shay and his colleagues analyzed the tissues of the fat mice that ate the supplements, they noted higher activity levels of PPAR-alpha and PPAR-gamma, two proteins that work within cells to metabolize fat and sugar. Shay hypothesizes that the ellagic acid and other chemicals bind to these PPAR-alpha and PPAR-gamma nuclear hormone receptors, causing them to switch on the genes that trigger the metabolism of dietary fat and glucose. Commonly prescribed drugs for lowering blood sugar and triglycerides act in this way, Shay said. The goal of his work, he added, is not to replace needed medications but to guide people in choosing common, widely available foods that have particular health benefits, including boosting metabolic function. "We are trying to validate the specific contributions of certain foods for health benefits," he said. "If you're out food shopping, and if you know a certain kind of fruit is good for a health condition you have, wouldn't you want to buy that fruit?" The research was supported by the Institute of Food and Agricultural Science at the University of Florida and Florida Department of Agriculture and Consumer Services. The study appears in the January

 

Another breastfeeding benefit: Preparing baby's belly for solid food

 

The moment of birth marks the beginning of a beautiful, lifelong relationship between a baby and the billions of microbes that will soon colonize his or her gastrointestinal tract. In a study published today in Frontiers in Cellular and Infection Microbiology, researchers from the UNC School of Medicine and UNC College of Arts and Sciences found that a baby's diet during the first few months of life has a profound influence on the composition, diversity, and stability of the gut microbiome. These factors, in turn, influence the baby's ability to transition from milk to solid foods and may have long-term health effects. "We found that babies who are fed only breast milk have microbial communities that seem more ready for the introduction of solid foods," said Andrea Azcarate-Peril, PhD, assistant professor in the department of cell biology and physiology and the study's senior author. "The transition to solids is much more dramatic for the microbiomes of babies that are not exclusively breastfed. We think the microbiomes of non-exclusively breastfed babies could contribute to more stomach aches and colic." The discovery adds to the growing awareness that the gut microbiome plays a major role in helping us digest food and fight pathogens, among other functions. "This study provides yet more support for recommendations by the World Health Organization and others to breastfeed exclusively during the first six months of life," said Amanda Thompson, PhD, associate professor in the department of anthropology, a Carolina Population Center faculty fellow, and the study's first author. "We can see from the data that including formula in an infant's diet does change the gut bacteria even if you are also breastfeeding. Exclusive breastfeeding seems to really smooth out the transition to solid foods." For this study, the research team collected stool samples and information about the diets and health of nine babies as they grew from ages 2 weeks to 14 months. Applying genomic sequencing techniques to the stool samples, the scientists deduced the types and functions of the bacteria in the babies' gut microbiomes. The analysis revealed that during the first few months of life there were clear differences between the microbiomes of babies that were exclusively breastfed as compared to those fed both formula and breast milk. This finding is consistent with previous studies. What surprised Thompson and Azcarate-Peril, who is the director of the UNC Microbiome Core Facility, was the drastic genetic differences in stool samples taken after babies began eating solid food. Researchers found differing amounts of about 20 bacterial enzymes in exclusively breastfed babies when compared to exclusively breastfed babies that received solid food. This indicated that some new bacterial species had entered the scene to help process the new food types. In babies fed both formula and breast milk -- and then introduced to solid foods -- the samples revealed about 230 enzymes, indicating a much more dramatic shift in microbial composition. The microbiomes of exclusively breastfed babies tended to be less diverse and were dominated by Bifidobacterium, a type of bacteria considered beneficial for digestion. Babies fed a mixture of breast milk and formula had a lower proportion of Bifidobacterium. The study suggests that the makeup of the microbiome can affect a baby's ability to digest food in the short term and potentially influence long-term health. Although microbiome research is still in its early stages, gut microbes are thought to potentially play a role in obesity, allergies, and gastrointestinal problems, such as irritable bowel syndrome. "The study advances our understanding of how the gut microbiome develops early in life, which is clearly a really important time period for a person's current and future health," said Thompson. The researchers also compared the microbiomes of babies that attended daycare to those that stayed in the home. Attending daycare was also associated with more diverse microbial communities overall, but feeding practices remained the most important factor influencing how the microbiome responded to the introduction of solid foods.

 

Organic food reduces pesticide exposure

 

While health-conscious individuals understand the benefits of eating fresh fruits and veggies, they may not be aware of the amount of pesticides they could be ingesting along with their vitamin C and fiber. A new study to be published in the Feb. 5 edition of Environmental Health Perspectives is among the first to predict a person's pesticide exposure based on information about their usual diet. The study was led by Cynthia Curl, an assistant professor in Boise State University's School of Allied Health Sciences. She recently joined Boise State from the University of Washington. Curl and her colleagues analyzed the dietary exposure of nearly 4,500 people from six U.S. cities to organophosphates (OPs), the most common insecticides used on conventionally grown produce in the United States. OP pesticides are linked to a number of detrimental health effects, particularly among agricultural workers who are regularly exposed to the chemicals. Results showed that among individuals eating similar amounts of fruits and vegetables, those who reported eating organic produce had significantly lower OP pesticide exposures than those consuming conventionally grown produce. In addition, consuming those conventionally grown foods typically treated with more of these pesticides during production, including apples, nectarines and peaches, was associated with significantly higher levels of exposure. "For most Americans, diet is the primary source of OP pesticide exposure," said Curl "The study suggests that by eating organically grown versions of those foods highest in pesticide residues, we can make a measurable difference in the levels of pesticides in our bodies." This study included dietary data collected from participants in the Multi-Ethnic Study of Atherosclerosis, a large, multi-institutional project funded by the National Heart, Lung and Blood Institute that is investigating factors that influence the onset of cardiovascular disease. The researchers were able to predict each participant's exposure to OP pesticides based on the amount and type of produce each participant typically ate and the U.S. Department of Agriculture's measurements of pesticide residue levels on those foods. The researchers then compared these predictions to pesticide metabolite levels measured in urine samples from a subset of 720 of these people. While Curl's study is not the first to link organic produce with reduced pesticide exposure, the method she used may have significant implications for future research. By combining self-reported information on typical food consumption with USDA measurements, researchers will be able to conduct research on the relationship between dietary pesticide exposure and health outcomes in bigger populations, without needing to measure urinary metabolites. "If we can predict pesticide exposure using dietary questionnaire data, then we may be able to understand the potential health effects of dietary exposure to pesticides without having to collect biological samples from people," Curl said. "That will allow research on organic food to be both less expensive and less invasive." "The next step is to use these exposure predictions to examine the relationship between dietary exposure to pesticides and health outcomes, including neurological and cognitive endpoints. We'll be able to do that in this same population of nearly 4,500 people," she said. One way people can reduce their pesticide exposure, said Curl, is to eat organic versions of those foods that are listed on the Environmental Working Group's "Dirty Dozen" list, which ranks fruits and vegetables according to pesticide residue level.

 

Malocclusion and dental crowding arose 12,000 years ago with earliest farmers

 

Hunter-gatherers had almost no malocclusion and dental crowding, and the condition first became common among the world's earliest farmers some 12,000 years ago in Southwest Asia, according to findings published (04 Feb 2015) in the journal PLOS ONE. By analysing the lower jaws and teeth crown dimensions of 292 archaeological skeletons from the Levant, Anatolia and Europe, from between 28,000-6,000 years ago, an international team of scientists have discovered a clear separation between European hunter-gatherers, Near Eastern/Anatolian semi-sedentary hunter-gatherers and transitional farmers, and European farmers, based on the form and structure of their jawbones. "Our analysis shows that the lower jaws of the world's earliest farmers in the Levant, are not simply smaller versions of those of the predecessor hunter-gatherers, but that the lower jaw underwent a complex series of shape changes commensurate with the transition to agriculture," says Professor Ron Pinhasi from the School of Archaeology and Earth Institute, University College Dublin, the lead author on the study. "Our findings show that the hunter gatherer populations have an almost "perfect harmony" between their lower jaws and teeth," he explains. "But this harmony begins to fade when you examine the lower jaws and teeth of the earliest farmers." In the case of hunter-gatherers, the scientists from University College Dublin, Israel Antiquity Authority, and the State University of New York, Buffalo, found a correlation between inter-individual jawbones and dental distances, suggesting an almost "perfect" state of equilibrium between the two. While in the case of semi-sedentary hunter-gatherers and farming groups, they found no such correlation, suggesting that the harmony between the teeth and the jawbone was disrupted with the shift towards agricultural practices and sedentism in the region. This, the international team of scientists say, may be linked to the dietary changes among the different populations. The diet of the hunter-gatherer was based on "hard" foods like wild uncooked vegetables and meat, while the staple diet of the sedentary farmer is based on "soft" cooked or processed foods like cereals and legumes. With soft cooked foods there is less of a requirement for chewing which in turn lessens the size of the jaws but without a corresponding reduction in the dimensions of the teeth, there is no adequate space in the jaws and this often results in malocclusion and dental crowding. The link between chewing, diet, and related dental wear patterns is well known in the scientific literature. Today, malocclusion and dental crowding affects around one in five people in modern-world populations. The condition has been described as the "malady of civilization."

 

How a basic building block of the body could prevent breast cancer

 

Preventing cancer requires intimate knowledge of how cancer starts, what causes it to grow and flourish, and how to stop it in its tracks. Sometimes this comes in the form of a vaccine (the HPV vaccine for cervical and head and neck cancers), a screening (a colonoscopy for colorectal cancer) or a blood test (the PSA level test for prostate cancer). Carol Fabian, M.D., co-leader of The University of Kansas Cancer Center Cancer Prevention Program and the Morris Family Endowed Chair in Cancer Prevention, is leading a study for women with a higher risk of breast cancer that focuses on two natural approaches to preventing breast cancer: weight loss and omega-3 fatty acids EPA and DHA. "Women in this study have a family history of breast cancer or a previous biopsy showing precancerous breast disease," said Dr. Fabian. "Prior to entering the study, they have their breast tissue tested and are found to have too many cells in the breast ducts, called hyperplasia. Their blood and breast tissues are also tested for other risk factors for breast cancer." All the women in the trial are placed on a calorie-restricted diet, along with support from a nutritionist and online weight loss and exercise tracking tools. Their goal is to lose 10 percent of their body weight in the first six months and maintain it in the second six months. In addition, half of the participants are given a high-dose omega-3 supplement while the other half are given a placebo. Their blood and breast tissue is tested again at six and 12 months. Periodically, the women's biomarker levels will be tested. Research has already shown a link between obesity and breast cancer risk. Abnormal fat cells increase the amount of hormones as well as inflammation in the body. The majority of breast cancers are fueled by hormones such as estrogen, and it is likely that some breast cancers are stimulated by inflammation as well. Previous studies by Dr. Fabian and her team showed that if an overweight or obese person loses at least 10 percent of their body weight, there's a reduction in hormone production and fewer inflammatory biomarkers. "The challenge is keeping those extra pounds off," she said, as anyone who has lost any amount of weight knows. As a result, Dr. Fabian is seeing if higher doses of the omega-3 fatty acids EPA and DHA would help with weight loss maintenance as well as favorably reduce risk biomarkers for breast cancer. Omega-3 fatty acids have multiple important body functions, such as cell signaling, proper immune system function and improving cognitive function. Higher dose EPA and DHA (fish oil supplements) are already used for prevention of cardiovascular diseases and to help with inflammatory disorders such as rheumatoid arthritis and irritable bowel disorder. The omega-3 fatty acids are primarily found in fatty cold water fish such as salmon and leafy green vegetables, which typically aren't eaten in abundance. A schema of Dr. Fabian's omega-3 and weight loss trial and when the presence of breast cancer biomarkers is measured. Dr. Fabian first got the idea to study omega-3 fatty acids and how they might affect cancer after hearing about a "miracle" food for dogs with mammary cancer or lymphoma. "Six years ago I heard about this Topeka, Kan., company named Hill's Pet Nutrition, which was founded by veterinarians and manufactured a special diet dog formulation. It didn't cure cancer, but it helped dogs with these cancers of an advanced stage live for a long time," said Dr. Fabian. "So I asked what was in it, and they said it was a really high dose of omega-3." The specific omega-3 fatty acids that are most beneficial to humans are DHA and EPA, which are mostly found in fatty, cold water fish. The average person only ingests about 100 milligrams of EPA and DHA a day when they should be getting about 30 times that amount. Dr. Fabian has already done a study looking at how omega-3 fatty acids work in pre- and postmenopausal women with an increased risk for breast cancer. The amount of a specific inflammatory biomarker, MCP1, was decreased in the women taking an omega-3 supplement. Previous research has also shown that omega-3 in particular seems to affect similar reward brain pathways as weight loss does. Does this mean taking an omega-3 supplement can help people who have already lost weight keep it off by keeping those brain pathways active? "Omega-3 seems to affect the same pathways in the brain as losing weight," explained Dr. Fabian. "If we could help people who have lost weight from gaining it back, that would be a big help in reducing their cancer risk. We want to see if omega-3 can improve the biomarker risk factor along with the weight loss and if it will make the maintenance phase easier." Several scientists are working with Dr. Fabian on this project, including Bruce Kimler, PhD, in Radiation Biology, and Steve Hursting, PhD, MPH, a basic scientist working on obesity from the University of North Carolina at Chapel Hill. Susan Carlson, PhD, is measuring fatty acid levels, Christie Befort, PhD, and Debra Sullivan, PhD, are in charge of the weight loss aspects and Jennifer Klemp, PhD, is examining quality of life. Two unique features of this grant are to determine whether EPA and DHA change bacteria in the colon associated with inflammation and whether these omega -3 fatty acids change reward center responses to food. "Certain types of bacteria increase inflammation in the colon, which increases the risk for colon cancer and likely other diseases too," said Dr. Fabian. "We're seeing if anything changes with the omega-3, and I'm convinced it will." Shadid Umar, PhD, KU Cancer Center member and associate professor in molecular and integrative physiology, is determining whether EPA and DHA have a favorable effect on gut bacteria. Women are also undergoing a functional brain MRI after six months of weight loss with or without the EPA and DHA. Cary Savage, PhD, director of the Center for Health Behavior Neuroscience at the University of Kansas Medical Center, Laura Martin, PhD, associate director of functional MRI and William Brooks, PhD, director of the Hoglund Brain Imaging Center, are looking at the brain's response to food after weight loss via MRIs.

 

Insulin-decreasing hormone discovered in flies, humans

 

An insulin-regulating hormone that, until now, only had been postulated to exist has been identified by researchers at the Stanford University School of Medicine. The hormone, called limostatin after the Greek goddess of starvation, Limos, tamps down circulating insulin levels during recovery from fasting or starvation. In this way, it ensures that precious nutrients remain in the blood long enough to rebuild starving tissues, rather than being rapidly squirreled away into less-accessible fat cells. The researchers first discovered limostatin in fruit flies but then quickly identified a protein with a similar function in humans. "Starvation or famine is an ancient, ever-present specter faced by all living organisms," said Seung Kim, MD, PhD, professor of developmental biology. "The ways to deal with it metabolically are likely to be ancient and conserved. This research clearly connects the dots between flies and humans, and identifies a new potential way to regulate insulin output in humans." In particular, members of a family with an inherited mutation in the human analog of limostatin exhibited many of the same physiological characteristics as flies genetically engineered to be unable to produce limostatin -- namely, high levels of circulating insulin, low blood sugar levels and a tendency toward early onset obesity. A paper describing the research findings will be published Feb. 3 in Cell Metabolism. Kim is the senior author, and graduate student Ronald Alfa is the lead author. The metabolic dance Insulin is a key player in the complicated metabolic dance shared by nearly all organisms. Its importance can hardly be overstated. After a meal, animals and humans produce insulin in response to the increase in blood sugars that occur as a meal is digested. This insulin stimulates the storage of circulating sugars into muscle and fat cells for future use. Too little insulin, or an inability of the body to respond correctly to its signal, causes a dangerous spike in blood sugar levels. Conversely, too much insulin can cause a rapid drop. Both conditions can be life-threatening, and ongoing swings in blood sugar levels can lead to complications, such as blindness, poor circulation and kidney failure. "This work has critical ramifications for our understanding of metabolism, and has the potential to transform our approach to treating diseases like diabetes," said Domenico Accili, MD, director of the Columbia University Diabetes and Endocrinology Research Center and Columbia's Russell Barry Foundation Professor of Diabetes. "The discovery of limostatin, a new hormone that can act to decrease insulin release, is an important advance," added Accili, who was not involved with the research. "The notion that mammals express a related family of intestinal hormones that can affect insulin secretion may inform new efforts to find drugs that combat diabetes in humans." Limostatin was identified by virtue of its response to fasting. Kim and his colleagues withheld food from their laboratory fruit flies for 24-28 hours and looked to see which genes were highly expressed during this time. They narrowed the list to those genes that encoded proteins resembling hormones, which are special signaling molecules that circulate throughout the body to affect the function of distant cells. They observed that one of these, limostatin, caused characteristics of insulin deficiency when overexpressed in flies. More fat cells, shorter life span Kim and his colleagues then genetically engineered a strain of flies unable to express limostatin. They found that these flies had too much circulating insulin. As a result, the animals had abnormally low levels of circulating sugars and more than the usual number of fat cells as they packed on the micro-pounds. Their life span was also shortened. The researchers found that, in flies, limostatin is produced by nutrient-sensing cells in the gut. It then circulates through the animal to reach the cells responsible for producing insulin. In flies, these are in the brain; in humans, insulin is produced by beta cells in the pancreas. Limostatin binds to the cells via a receptor protein on their surfaces, reducing the amount of insulin they secrete. Blocking the expression of this receptor in flies, the researchers found, affected the insects in the same way as if they couldn't express limostatin. Once the researchers had identified the receptor for limostatin in fruit flies, they looked to see if it resembled any human protein. A trail of biological breadcrumbs led them to the receptor for a protein called Neuromedin U. The protein is produced in the brain, and controls a variety of physiological responses including smooth muscle contraction, blood pressure control, appetite and hormone function in humans. Based on their experiments in fruit flies, Kim and his colleagues expected that Neuromedin U might also be important in insulin regulation. They found that the protein is also expressed in the stomach and intestines, and the Neuromedin U receptor is found on insulin-producing beta cells in the pancreas. Neuromedin U and its receptor appeared to neatly connect nutrient sensing in the gut with insulin-producing cells elsewhere in the body. To confirm their finding, the researchers tested the effect of physiological levels of Neuromedin U on human pancreatic beta cells in the laboratory. They found that the hormone bound to the beta cells and blocked their ability to secrete insulin in response to an increase in glucose in their environment. Finally, they were able to connect what they saw in the lab to a naturally occurring mutation in humans. "We found a variant of this hormone that is mutated in a human family," said Kim. "Members of this family who inherited this mutation have early onset obesity and diabetes, and some have abnormally high insulin levels. We predicted that this variant would cause a loss of function in our laboratory assay of insulin secretion, and that is what we found." In short, the same mutant form of Neuromedin U that was shared by affected family members was unable to suppress insulin secretion in the laboratory-grown beta cells. "These experiments were a linchpin linking what we saw in the laboratory to human physiology," said Kim. A 19th-century theory confirmed Limostatin belongs to a class of hormones called decretins, which have been suspected to exist for about 150 years, starting with work by the renowned French physiologist Claude Bernard. In 1932, researchers identified a class of hormones called incretins, which were expressed in the gut after a meal and stimulated insulin secretion. Other metabolic studies, including those on animals and people undergoing starvation conditions, suggested that another class of hormone might function to suppress insulin production during times of famine. A phenomenon was termed "starvation diabetes" to describe how rapid re-feeding with glucose or carbohydrate-rich foods after a fast can cause diabetes-like symptoms of abnormally high blood sugars and low insulin production. The discovery of limostatin, a decretin, further validates the use of fruit flies as a diabetes model, according to Kim. It may also explain a puzzling phenomenon that often occurs after bariatric surgery. The procedure, which removes a portion of the stomach to enable weight loss in obese people, often rapidly reverses ongoing or incipient signs of diabetes long before any pounds are shed.

 

Insulin-decreasing hormone discovered in flies, humans

 

An insulin-regulating hormone that, until now, only had been postulated to exist has been identified by researchers at the Stanford University School of Medicine. The hormone, called limostatin after the Greek goddess of starvation, Limos, tamps down circulating insulin levels during recovery from fasting or starvation. In this way, it ensures that precious nutrients remain in the blood long enough to rebuild starving tissues, rather than being rapidly squirreled away into less-accessible fat cells. The researchers first discovered limostatin in fruit flies but then quickly identified a protein with a similar function in humans. "Starvation or famine is an ancient, ever-present specter faced by all living organisms," said Seung Kim, MD, PhD, professor of developmental biology. "The ways to deal with it metabolically are likely to be ancient and conserved. This research clearly connects the dots between flies and humans, and identifies a new potential way to regulate insulin output in humans." In particular, members of a family with an inherited mutation in the human analog of limostatin exhibited many of the same physiological characteristics as flies genetically engineered to be unable to produce limostatin -- namely, high levels of circulating insulin, low blood sugar levels and a tendency toward early onset obesity. A paper describing the research findings will be published Feb. 3 in Cell Metabolism. Kim is the senior author, and graduate student Ronald Alfa is the lead author. The metabolic dance Insulin is a key player in the complicated metabolic dance shared by nearly all organisms. Its importance can hardly be overstated. After a meal, animals and humans produce insulin in response to the increase in blood sugars that occur as a meal is digested. This insulin stimulates the storage of circulating sugars into muscle and fat cells for future use. Too little insulin, or an inability of the body to respond correctly to its signal, causes a dangerous spike in blood sugar levels. Conversely, too much insulin can cause a rapid drop. Both conditions can be life-threatening, and ongoing swings in blood sugar levels can lead to complications, such as blindness, poor circulation and kidney failure. "This work has critical ramifications for our understanding of metabolism, and has the potential to transform our approach to treating diseases like diabetes," said Domenico Accili, MD, director of the Columbia University Diabetes and Endocrinology Research Center and Columbia's Russell Barry Foundation Professor of Diabetes. "The discovery of limostatin, a new hormone that can act to decrease insulin release, is an important advance," added Accili, who was not involved with the research. "The notion that mammals express a related family of intestinal hormones that can affect insulin secretion may inform new efforts to find drugs that combat diabetes in humans." Limostatin was identified by virtue of its response to fasting. Kim and his colleagues withheld food from their laboratory fruit flies for 24-28 hours and looked to see which genes were highly expressed during this time. They narrowed the list to those genes that encoded proteins resembling hormones, which are special signaling molecules that circulate throughout the body to affect the function of distant cells. They observed that one of these, limostatin, caused characteristics of insulin deficiency when overexpressed in flies. More fat cells, shorter life span Kim and his colleagues then genetically engineered a strain of flies unable to express limostatin. They found that these flies had too much circulating insulin. As a result, the animals had abnormally low levels of circulating sugars and more than the usual number of fat cells as they packed on the micro-pounds. Their life span was also shortened. The researchers found that, in flies, limostatin is produced by nutrient-sensing cells in the gut. It then circulates through the animal to reach the cells responsible for producing insulin. In flies, these are in the brain; in humans, insulin is produced by beta cells in the pancreas. Limostatin binds to the cells via a receptor protein on their surfaces, reducing the amount of insulin they secrete. Blocking the expression of this receptor in flies, the researchers found, affected the insects in the same way as if they couldn't express limostatin. Once the researchers had identified the receptor for limostatin in fruit flies, they looked to see if it resembled any human protein. A trail of biological breadcrumbs led them to the receptor for a protein called Neuromedin U. The protein is produced in the brain, and controls a variety of physiological responses including smooth muscle contraction, blood pressure control, appetite and hormone function in humans. Based on their experiments in fruit flies, Kim and his colleagues expected that Neuromedin U might also be important in insulin regulation. They found that the protein is also expressed in the stomach and intestines, and the Neuromedin U receptor is found on insulin-producing beta cells in the pancreas. Neuromedin U and its receptor appeared to neatly connect nutrient sensing in the gut with insulin-producing cells elsewhere in the body. To confirm their finding, the researchers tested the effect of physiological levels of Neuromedin U on human pancreatic beta cells in the laboratory. They found that the hormone bound to the beta cells and blocked their ability to secrete insulin in response to an increase in glucose in their environment. Finally, they were able to connect what they saw in the lab to a naturally occurring mutation in humans. "We found a variant of this hormone that is mutated in a human family," said Kim. "Members of this family who inherited this mutation have early onset obesity and diabetes, and some have abnormally high insulin levels. We predicted that this variant would cause a loss of function in our laboratory assay of insulin secretion, and that is what we found." In short, the same mutant form of Neuromedin U that was shared by affected family members was unable to suppress insulin secretion in the laboratory-grown beta cells. "These experiments were a linchpin linking what we saw in the laboratory to human physiology," said Kim. A 19th-century theory confirmed Limostatin belongs to a class of hormones called decretins, which have been suspected to exist for about 150 years, starting with work by the renowned French physiologist Claude Bernard. In 1932, researchers identified a class of hormones called incretins, which were expressed in the gut after a meal and stimulated insulin secretion. Other metabolic studies, including those on animals and people undergoing starvation conditions, suggested that another class of hormone might function to suppress insulin production during times of famine. A phenomenon was termed "starvation diabetes" to describe how rapid re-feeding with glucose or carbohydrate-rich foods after a fast can cause diabetes-like symptoms of abnormally high blood sugars and low insulin production. The discovery of limostatin, a decretin, further validates the use of fruit flies as a diabetes model, according to Kim. It may also explain a puzzling phenomenon that often occurs after bariatric surgery. The procedure, which removes a portion of the stomach to enable weight loss in obese people, often rapidly reverses ongoing or incipient signs of diabetes long before any pounds are shed.