Links between gut bacteria and obesity

A new Johns Hopkins study of mice with the rodent equivalent of metabolic syndrome has added to evidence that the intestinal microbiome-a "garden" of bacterial, viral and fungal genes plays a substantial role in the development of obesity and insulin resistance in mammals, including humans.

Highlighting the potential to prevent obesity and diabetes by manipulating levels and ratios of gut bacteria, and modifying the chemical and biological pathways for metabolism-activating genes.

Metabolic syndrome, a cluster of conditions including obesity around the waist, high blood sugar and increased blood pressure, is a risk factor for heart disease, stroke and diabetes. While no precise cause for metabolic syndrome is known, previous studies of Toll-like receptor 4 (TLR4), a protein that receives chemical signals to activate inflammation, have suggested that TLR4 may be responsible in part for its development.

TLR4 signaling in different cells and their association with the bacterial environment could result in different effects on the development of metabolic syndrome. To determine whether TLR4 specifically in the intestinal epithelium (layer of cells that line the small and large intestines) would cause the development of metabolic syndrome, the research team ran a series of experiments on normal mice and mice genetically modified to lack TLR4 in their intestinal epithelium.

The researchers fed both groups of mice "standard chow," with 22 percent fat calories, for 21 weeks. Compared to normal mice, those lacking TLR4 showed a series of symptoms consistent with metabolic syndrome, such as significant weight gain, increased body and liver fat, and insulin resistance. The researchers then fed both groups of mice a high-fat diet comprised of 60 percent fat calories for 21 weeks to find out whether diet would affect the development of metabolic syndrome.

The genetically modified mice gained significantly more in weight and had greater body and liver fat than the normal mice. To confirm the role of TLR4 expression in the intestinal epithelium, the researchers genetically modified three more groups of mice: one group expressed TLR4 only in the intestinal epithelium, another group lacked TLR4 in all body cells and the third group lacked TLR4 only in white blood cells.

All groups ate standard chow, and all groups had similar body weight, body and liver fat, and glucose tolerance compared to normal mice. Compared with normal mice, belly and small intestine fat was higher in mice lacking TLR4 only in the intestinal epithelium. This, the researchers say, provides further evidence that deleting TLR4 specifically from the intestinal epithelium is required for developing metabolic syndrome.

To investigate the role the bacterial makeup of the gut had on the mice, they administered antibiotics to the normal and TLR4 intestinal epithelium-deficient mice. Antibiotics significantly reduced the amount of bacteria in the intestinal tract and prevented all symptoms of metabolic syndrome in the mice that lacked TLR4 in their intestinal epitheliums.

This shows that bacterial levels can be manipulated to prevent the development of metabolic syndrome. To further explore the role of intestinal epithelial TLR4 on the development of metabolic syndrome, the research team analyzed fecal samples from the TLR4 intestinal epithelium-deficient and normal mice.

The team found that specific clusters of bacteria that contribute to the development of metabolic syndrome were expressed differently in the deficient mice than in normal mice. They also determined that the bacteria expressed genes that made them "less hungry" and thus less able to digest the nutrients present in the mouse chow. This resulted in a greater abundance of food for the mouse to absorb, which contributed to obesity.

The researchers then analyzed the genes expressed in the lining of the intestinal mucosa-the site at which food absorption occurs in normal and TLR4 intestinal epithelium -deficient mice. Of note, the team determined that important genes in the perixisome proliferator-activated receptor (PPAR) metabolic pathway were significantly suppressed in the deficient mice.

Administering antibiotics prevented the differences in gene regulation between the two groups of mice, as did administering drugs to activate the PPAR signaling pathway. The bacterial sensor TLR4 regulates both host and bacterial genes that play unrecognized roles in energy metabolism leading to the development of metabolic syndrome in
mice.
          haleplushearty.blogspot.com

Environmental influence can change gene behaviour

In a study of pregnant women, a team of Deakin scientists has shown in humans for the first time that pregnancy can induce long-term epigenetic changes to human body, with major implications for understanding, preventing and treating disease. Deakin University scientists have discovered that pregnancy can cause long-term changes to the way women's genes behave, which could affect the health of mother and children.

The findings of a recent study from Deakin's Centre for Cellular and Molecular Biology, within the School of Life and Environmental Sciences, showed women experience major molecular changes during pregnancy that could remain with them after their pregnancy has ended. The changes are "epigenetic"-they are not a mutation of the gene's structure, but a change to how genes behave.

Long-term epigenetic changes can lead to increased risks of disease for the next generation. Studies have previously shown the offspring of women with diabetes have an increased risk of developing obesity, glucose intolerance and type 2 diabetes. Epigenetic markers act like a switch that can alter the activity of genes and cells in the body. All individual cells have the same genetic material, but the behaviour of a gene is different in different tissues of the body. That behaviour can be determined by epigenetic factors, independent of the DNA sequences of the genes.

Epigenetics has implications for understanding, preventing and combatting many diseases, from diabetes to cancer, providing understanding of how adverse environmental factors, including lifestyle, can cause disease. Researchers compared groups of never-pregnant women, pregnant women, and women at 20 weeks postpartum, and made comparisons between the same groups of women at pregnancy, at eight to 10 weeks postpartum, and at 20 weeks postpartum. Similar comparisons were carried out among women with type 2 diabetes.

A significant finding was that women with type 2 diabetes had different epigenetic profiles from non-diabetic women, and their profiles underwent different changes during pregnancy. Pregnancy-induced epigenetic changes could lead to complications among these women with diabetes, such as downstream effects that may contribute to insulin resistance, as well as high risk pregnancy outcomes. Maternal malnutrition and other adverse events in pregnancy can cause problems for the next generation due to epigenetics.
           haleplushearty.blogspot.com

Sitting for long hours linked to visceral fat

Sitting for long hours leads to building of fat around the body's organs and increases the risk of type 2 diabetes and heart disease. A study found people who spent a large amount of time sitting down had higher levels of visceral and total abdominal fat. Visceral fat is unseen and wrapped around the liver, pancreas and kidneys. Carrying a high amount is known to be associated with insulin resistance - the driving factor for type 2 diabetes.

There's a difference between subcutaneous fat, the type of fat that lies directly under the skin and visceral fat, which is unseen and around human organs. According to an expert, slim-looking people can have this dangerous fat on the inside, that's wrapped around the liver, pancreas and kidneys.
Visceral abdominal fat is also linked to an increased risk of cancer, stroke and heart disease. Researchers used MRI to scan  participants who were likely to develop type 2 diabetes. They also used ccelerometers that were placed around their waists to measure how much time these people spent sitting over the course of a week.

The researchers found that the link between visceral fat and sitting was strongest for those who did not meet the public health recommendation of 150 weekly minutes of moderate-intensity physical activity. Using MRI techniques and physical activity monitors have shown that the more time spent sedentary, the stronger the association with higher levels of internal and abdominal fat. This was particularly so if the long periods of sedentary behavior were uninterrupted.

When cortisol the stress hormone is too high for too long, it can increase the amount of fat that's stored around the stomach. Dieting alone is not enough combining healthy eating with stress management techniques can help. Cortisol is created in the body’s adrenal gland, it is essential to give get-up-and-go human need to get motivated and focused, which is why it’s usually elevated in the morning. It's also released during exercise and periods of acute stress. It regulates energy by selecting the right amount of carbohydrate, fat, or protein the body needs to meet the physiological demands placed on it.

Cortisol is released from the body’s adrenal glands and floods the body with glucose  when the body is stressed, the simplest form of carbohydrate and preferred energy source – to give muscles an immediate supply of energy. Insulin-the hormone that reduces blood sugar – is also released to prevent the glucose being stored as fat and make it freely available to give the immediate energy to deal with an event. Hormone balance will returns to normal when stress is reduce.
          haleplushearty.blogspot.com

Kidney disease can cause diabetes

Urea plays a role in the two-way link between the two diseases. Urea comes from the breakdown of protein in food. Kidneys normally remove urea from the blood, but poor kidney function can lead to increased levels of urea.

The study involved the analysis of medical records of adults who did not have diabetes. About 9 percent had elevated urea levels, a sign of reduced kidney function. That's the same rate as in the general population, according to the researchers.

People with high urea levels were 23 percent more likely to develop diabetes than those with normal urea levels, the study found. Diabetes is a major risk factor for kidney disease, elevated levels of urea, also raises the risk of diabetes.

When urea builds up in the blood because of kidney dysfunction, increased insulin resistance and impaired insulin secretion often result.
          haleplushearty.blogspot.com

Kidney disease increases the risk of diabetes

Diabetes is known to increase the risk of kidney disease, kidney dysfunction also increases the risk of diabetes. The two-way relationship between kidney disease and diabetes is urea. The nitrogen-containing waste product in blood comes from the breakdown of protein in foods.

Kidneys normally remove urea from the blood, but it can build up when kidney function slows down. The findings are significant because urea levels can be lowered through medication, diet-for example, by eating less protein-and other means, thereby allowing for improved treatment and possible prevention of diabetes.

When urea builds up in the blood because of kidney dysfunction, increased insulin resistance and impaired insulin secretion often result. Researchers evaluated the records of different adults without diabetes over a five-year period, blood test that measures the amount of urea nitrogen found in the blood showed that some of them had elevated urea levels, signaling poor kidney function.
          haleplushearty.blogspot.com

Diabetes has hepatic origins

Obesity increases the risk of developing metabolic conditions, and primarily type 2 diabetes. The molecular mechanisms by which obesity predisposes people to the development of insulin resistance are so far poorly understood. By deciphering how the protein PTPR-γ, which is increased in obesity, inhibits insulin receptors located at the surface of liver cells, the scientists open the door to potential news therapeutic strategies.

The expansion of fat cells, a characteristic of obesity, leads to an increase in inflammatory signals that have effects on the liver as well as on several other organs. Obesity-induced inflammation triggers the activation of a transcription factor called NF-kβ, which seems to be instrumental in the development of diabetes. Researchers examined various human cohorts-these human studies indicated that PTPR-γ content in liver increases upon inflammation, an effect that could directly affect insulin receptors by inhibiting insulin action.

The scientists modified the levels of PTPR-γ expression in mice, by either suppressing, normally expressing or overexpressing it, and observed the effect on insulin resistance. The mice totally lacking PTPR-γ, when put on a high-calorie diet, did develop obesity. But they did not show any sign of insulin resistance and seemed to be entirely protected from diet-induced diabetes. They also administered lipopolysaccharide, a toxin pertaining to certain bacteria of the gut microbiota associated with obesity and insulin resistance. Once again, the animals lacking PTPR-γ did not develop insulin resistance.

They reconstituted the expression of PTPR-γ at normal levels, but only in hepatocytes (liver cells ). The mice were again prone to insulin resistance, indicating the pivotal role of the liver. Moreover, a two-fold overexpression in the liver (mimicking the natural pathophysiology of obesity was sufficient to cause insulin resistance. The metabolic functions of this protein were never characterized; this discovery therefore opens the door for potential new therapies.

The very form of this protein allows for potential inhibition strategies: when two independent PTPR-γ molecules are brought together by a ligand, they cannot act any more. The researchers are now working on identifying the endogenous ligand produced by the body, or on developing molecules that could mimic its function.
           haleplushearty.blogspot.com

Drinking of alcohol and metabolic factors increase the risk of liver disease

There is an increasing burden of liver disease and liver cancer. The metabolic syndrome and heavy alcohol consumption are associated with increased risks of liver disease, although only a minority of patients with early-stage liver disease (e.g. fatty liver) develop liver failure or liver cancer. Few general population studies have analyzed metabolic predictors of such severe liver complications.

Researchers studied which metabolic factors best predict severe liver complications. Their analysis included people without liver disease who participated in the Finnish population-based Health 2000 Study (2000-2001). The researchers analyzed follow-up data on liver-related hospital admissions, mortality, and liver cancer from national registers.

Some of the participants experienced a severe liver event during follow-up. Factors predictive of liver events were older age, female gender, alcohol use, diabetes, LDL cholesterol, and insulin resistance. Among individuals who consumed higher amounts of alcohol (average alcohol use ?210 g/week for men, ?140 g/week for women), diabetes was the only significant predictor.

Among those who consumed less or no alcohol, older age, alcohol use, smoking, abdominal obesity, LDL cholesterol, and insulin resistance were significant predictors. Alcoholic liver disease ALD and non-alcoholic liver disease NAFLD are considered separate entities, distinguished from each other by an arbitrary threshold of average alcohol intake.

This diagnostic approach assumes that alcohol intake does not affect the course of NAFLD and that the metabolic syndrome is the hallmark of NAFLD is not a factor in ALD. This study reveals that alcohol is a relevant risk factor even when alcohol consumption is within the limits currently used to separate NAFLD from ALD.

Liver disease should perhaps not be considered in terms of mutually exclusive entities of ALD and NAFLD, because in a large number of patients with liver disease, the effect of alcohol is difficult, and sometimes impossible, to separate from the effect of metabolic factors.

 Alcohol use and metabolic factors are taken into account at the same time in order to identify individuals with a high risk for severe liver complications. For a comprehensive liver-risk assessment, lipid abnormalities, abdominal obesity, insulin resistance, diabetes, and alcohol use should all be considered at the same time.
          haleplushearty.blogspot.com

Low calorie diet can reverse type 2 diabetes

Diabetes goes into remission in many patients who undergo bariatric weight-loss surgery, which significantly restricts caloric intake prior to clinically significant weight loss.The research team investigated the effects of a very low calorie diet VLCD, consisting of one-quarter the normal intake, on a rodent model of type 2 diabetes.

Using a novel stable (naturally occurring) isotope approach, which they developed, the researchers tracked and calculated a number of metabolic processes that contribute to the increased glucose production by the liver. The method, known as PINTA, allowed the investigators to perform a comprehensive set of analyses of key metabolic fluxes within the liver that might contribute to insulin resistance and increased rates of glucose production by the liver-two key processes that cause increased blood-sugar concentrations in diabetes.

Using this approach, the researchers pinpointed three major mechanisms responsible for the VLCD's dramatic effect of rapidly lowering blood glucose concentrations in the diabetic animals. In the liver, the VLCD lowers glucose production by: decreasing the conversion of lactate and amino acids into glucose; decreasing the rate of liver glycogen conversion to glucose; and decreasing fat content, which in turn improves the liver's response to insulin.

These positive effects of the VLCD were observed in three days. Using this approach to comprehensively interrogate liver carbohydrate and fat metabolism, we showed that it is a combination of three mechanisms that is responsible for the rapid reversal of hyperglycemia following a very low calorie diet.
           haleplushearty.blogspot.com

Effects of different sugar on the liver

Concentrated sugars such as high-fructose corn syrup, a sugar found in sweetened beverages and many other processed foods have negative effects on liver. According to the latest research, mice on a fatty diet who were given high levels of fructose in their diet suffered worse metabolic effects than those given similar calories of glucose.

Researchers experimented in a mouse model used to study obesity, type 2 diabetes, fatty liver and other metabolic illnesses. These animals were given either regular or high-fat diets, and drank either plain water or water sweetened with fructose or glucose.
Comparing these diets, gave more precise role of fructose against glucose in the diet, and how bad is it when it is added to a normal diet against a diet high in fat. After two months, none of the animals on a regular diet developed insulin resistance.

Among animals on a high-fat diet, there is significant differences between those drinking fructose and glucose. Fatty liver disease does not progress to dangerous levels of liver inflammation,
Mice on the high-fat diet become much more obese and more insulin-resistant compared to their peers on the glucose diet. And while both groups of animals added fat to their livers, the fat composition was different.

The researchers also discovered that production of an enzyme called ketohexokinase KHk, required for the first step of fructose metabolism, was increased in the livers of mice who drank fructose. When the scientists examined liver samples from obese human with fatty liver disease, they also found higher levels of Khk. The Khk enzyme is important in fructose, but not glucose, metabolism. Fructose and glucose are sugars, cells handle them differently.
          haleplushearty.blogspot.com

Third-hand smoke exposure affects liver and kidney

Third-hand smoke exposure can damage brain, liver, increase the risk of neurodegenerative diseases, and destroy metabolism. The research team analyzed how people were affected by inhaling smoke from smoker's clothes, hair, home, or car.

Being a third-hand smoker for one month can cause type 2 diabetes, hyperactivity, liver and lung damage, and wound-healing complications.
Exposure for two months resulted in further molecular damage, and at four to six months caused more damage, long-term exposure can leads to insulin resistance.

Researchers discovered that stress hormones, such as epinephrine, increased in one month of exposure.
Additional stress hormones are seen at two months, four months, and six months, eventually leading to immune fatigue.

Contaminants can be absorbed through the skin and through breathing. Exposure to tobacco smoke deposited on surfaces in homes and dust is a new form of toxicity. Noxious chemicals in tobacco smoke once deposited change in chemistry to become even more toxic and carcinogenic.
          haleplushearty.blogspot.com

Fasting diet in a healthy way

Calories restrictions extends lifespan and prevents sicknesses and diseases. Fasting has been used for thousands of years for health benefits. It can improve glucose tolerance. Insulin resistance is generally caused as a result of the body's reduced ability to remove excess glucose from the blood either because insufficient insulin is released or the glucose receptors have become less sensitive.

Excess glucose will be converted to fat and stored in tissues not suitable for fat storage. As the body uses fat as a fuel during intermittent fasting, fat stores will reduce allowing the cells to regain insulin function and glucose sensitivity.
Intermittent fasting can improve pre-diabetic and insulin resistant.

 Short term intermittent fasting may be a safe and tolerable dietary intervention for those already diagnosed with Type 2 Diabetes and may improve body weight and reducing glucose levels. Fasting diet in a healthy way improves skin health. Intermittent fasting's ability to reduce weight will result in lower body fat. This improves heart function, prevents cancer and improves immune system.

Eat healthy foods during intermittent fasting to ensure the body's processes are taking place efficiently and effectively. Add fruits, vegetables, healthy fats and protein to every meal.
Reduce intake of junk foods and carbohydrates such as bread, pasta, potatoes and rice. The simple concept is to aim to fast every day for 16-18 hours a day and only consume food in the remaining six to eight hours.

 Increase the gap between dinner and breakfast; if you eat dinner at 6pm, then you would not eat your next meal until 12pm the following day, allowing an 18-hour fast in between. People that are underweight, sick or using drugs must not fast. Children, pregnant women and nursing mother should avoid fasting.
          haleplushearty.blogspot.com

Heart hormones prevent obesity and insulin resistance

Enhanced natriuretic peptide NP signaling in adipose tissue protects against obesity and insulin resistance. Boosting levels of NPs in adipose tissue may reduce the risk of metabolic disease. NPs control blood pressure and can promote the conversion of energy-storing 'bad' white fat into energy-burning 'good' brown fat.

Atrial and B-type natriuretic peptides NPs are hormones that were originally discovered to modulate salt and water to control blood pressure. These peptides transmit their signals through natriuretic peptide receptor NPRC. Natriuretic peptide receptor C (NPRC) removes NPs from circulation.

Researchers studied mice with NPRC receptors selectively knocked out in either adipose or skeletal muscle tissue. While deleting NPRC in muscle provided no protection from a high-fat diet, eliminating the receptor in adipose tissue improved insulin sensitivity, prevented obesity and increased sugar uptake in metabolism-boosting brown fat.

 The adipose knockout mice showed higher energy expenditure and less inflammation. In mice without NRPCs in adipose tissue the liver was completely clean and completely devoid of stored lipids, which leads to their improved overall metabolic performance.

Slim people tend to have higher NP concentrations in their blood while NP clearance tends to rise in fat tissue, removing these peptides from the blood and making it more difficult for effective NP signaling to occur. Obesity increases the risk of type 2 diabetes, metabolic syndrome, fatty liver disease and other conditions. Exploring NPs as therapeutic targets can prevents obesity.
          haleplushearty.blogspot.com

Causes of type 2 diabetes

Type 2 diabetes is a disorder of metabolism, the condition occurs when the body does not produce enough insulin or the insulin produced does not work properly.

Insulin resistance means that the cells of the body do not fully respond to insulin that is released. This makes glucose to remains in the blood instead of being moved into the cells.

Common symptoms of Type 2 diabetes are: extreme thirst, frequent urination fatigue, blurred vision, sudden weight loss and increased appetite.

It can reduce life expectancy if it is not managed properly and cause different health complications. These factors increase the risk of developing type 2 diabetes.

Age increases the risk of diabetes, diabetes is common among adults, aging and insulin resistance are closely connected because old people gain weight and become inactive.

Another risk factor is being overweight
especially if you are large around the middle because it increases pressure on body’s ability to use insulin properly to control blood sugar levels.

The pressure of blood flowing through the arteries varies at different times in the heartbeat cycle and the systolic pressure measures the pressure when heart contracts and blood is forced through the arteries. High blood pressure can increase the risk of type 2 diabetes.

Genetics can contribute to the risk of developing type 2 diabetes. Parents can transfer it to their children. Mutations in any gene involved in controlling glucose levels can increase risk of type 2 diabetes. These include genes that control: production of glucose, production and regulation of insulin and how glucose levels are measured in the body

High blood glucose levels during pregnancy may leads to the development of type 2 diabetes in future.

Healthy eating, an active lifestyle and regular medical examination can reduce the risk of type 2 diabetes.
          haleplushearty.blogspot.com

Benefits of calories reduction

When the body does not have enough glucose for energy, it burns stored fats, resulting in a build-up of molecules called ketone bodies.

Investigators suspect that calorie reduction extends life span at least in part through increasing levels of ketone bodies.

Aging-induced change like incidence of malignancies in mice, the increases in blood glucose and insulin caused by insulin resistance, and muscular weakness.

Insulin resistance can be decreased by the metabolism of ketone bodies, a normal metabolite produced from fatty acids by liver during periods of prolonged fasting or caloric reduction.

The more calorie you reduce, the less fat your body will accumulate. Less accumulation of fat in the body makes you healthy, it prevents diabetes and other terminal diseases.