Obesity causes lung dysfunction and breathing troubles by increased cysteinyl leukotrienes pathway

Increased body weight is a chronic health problem which has emanated from the globalized food market and dietary habit. This has led to the different types of ailments which occur in obese individual simultaneously and referred to as metabolic disorders. Metabolic syndrome includes conditions such as obesity, insulin-resistance, diabetes, hypertension, cardiovascular, and some forms of cancers. Lung dysfunction is also associated with increased body weight in which obese persons feel difficulty in breathing and could develop asthma like symptoms if not treated timely. Many studies have shown that such patients are difficult to treat with the regular asthma medicines, which suggests that probably breathing problem in obese people is caused by different mechanism and is different than allergic asthma. 

Elevated levels of cysteinyl leukotrienes (CysLTs) in the urine of obese asthma patients indicate elevated levels of biochemical pathway that forms this compound. CysLTs are responsible for the inflammation and swelling and can change the cell’s behavior by modifying their structure and function. In fact, LTs are known to cause lung problems in asthma and COPD in non-obese people and inhibitors of LTs receptors or of enzymes that make LTs are used as drug to treat such patients.

In the obese individual the fat deposits in the special cells called adipocytes which grows in number and size upon energy rich diet consumption. The adipocytes secret certain chemicals which attract macrophages, the policing cells in body which fight with pathogens and infectious agents and also some of the body’s own molecules and materials and removes them. In excessive accumulation of adipocytes, more macrophages get attracted to adipose tissue, get overactive and secrete molecules like cytokines, chemokines and also CysLTs which are released in blood and can cause inflammation in other body parts.

When it reaches to the lungs, CysLTs can activate the lung cells which can also secret the inflammation causing molecules and attract immune cells to the lungs. This scenario is similar to the early stage of development of asthma. Over the period of time these molecules can change the structure and function of lung cells including epithelial cells which can change into either mucous cells of fibrous cells and lung function may get severely affected. Mucous cells secret large amount of mucous which inhibit the gas exchange in the lung while fibrous cells affect the elasticity of the lung and lung cannot expand upon breathing.

How obesity causes these changes in the lungs is still not known and scientists are actively working to find answers. The mechanism once clear can help in treating such patients using the appropriate drugs.

Reference: Yadav UC, Srivastava SK. Cysteinyl Leukotrienes (CysLTs): Role in Obesity-Induced Asthma. Curr Mol Med. 2015; 15(7): 598-605.

  

Health Rhymes

Being evolved from nomads, hunter and gatherers, humans aught to remain mobile, active and runners.

Being sedentary is not healthy, that is not us. Sitting and laying make us filthy and creates pus.

Fast or slow but run, jump, squat, stretch, skip twist, bend and turn. Let the blood flow unhindered from top to toe and calories burn.

All them together or subsequently, but must you do them daily.

Call it Exercise, Yoga or Pilates. Practice them and stay away from trouble of heart and diabetes.

To stay fit, healthy, and athlete you must leave the bed, and your seat.

Kill the diseases whether diabetes, obesity, or heart failure. Play and laugh like a kid, do not get stressed like a mature.

Artificial Sweeteners Cause Metabolic Disorders

For the diabetics, obese and weight conscious individuals artificial sweeteners (AS) are considered safe choice to help regulate the blood glucose level and manage body weight. Use of AS considered good choice to sweeten the drinks and deserts as opposed to the common table sugar mostly due to low amount or lack of calorie in them.  Because of the same reason many food and beverage companies market their “calorie free” “Lite” and “diet” drinks and food items to cater the need of various “calorie conscious” customers.

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Food and drug administration (FDA) of USA identifies some of these sweeteners as “high-intensity sweeteners” and regulates them as food additive, meaning that they must undergo premarket review and approval by FDA before it can be used in food.  Accordingly nearly six artificial sweeteners have been approved by FDA as food additives in the USA. These are saccharin, aspartame, acesulfame potassium (Ace-K), sucralose, neotame, and advantame. The agency considers these FDA approved AS safe for the general population in certain conditions of use¹.  

The use of AS has become more common in general population due to reported ill effects of common sugar including sudden increase in blood sugar, tooth decay, weight gain, obesity, and an array of life style diseases such as hypertension, cardiovascular diseases, type 2 diabetes and dementia among others. The increased use of AS has propelled the scientists to examine the long-term effects of AS on humans.

In a recent study scientists have observed that use of AS may lead to the development of glucose intolerance (GI). GI is a hyperglycaemic state that is linked to insulin resistance and generally occurs in pre-diabetic individuals. AS induced glucose intolerance, scientists observed, develops due to alteration in the composition and function of the microorganism or microbiota that live in our intestine.

The group of scientists led by Jotham Suez² found that when mice were fed AS, they showed altered GI and also their intestinal microbiota composition changed from that of normal mice not fed AS. Further, when the intestinal microbiota from AS consuming mice was transferred to germ- free mice they also showed altered GI and other metabolic defects. These defective metabolisms were abrogated by the use of antibiotics which is known to kill the intestinal bacteria suggesting that the effects were caused due to the changed intestinal microbiota. 

When scientists compared the bacterial population from glucose-fed verses AS-fed mice by genetic analysis, they found that not only the composition, but the functions of the bacteria also had changed in AS-fed mice. The bacteria from AS-fed mice intestine showed increased carbohydrate degrading mechanisms. This means that they can degrade even complex carbohydrates easily leading to elevated glucose levels that may contribute to GI.

The scientists also examined and compared the intestinal microbiota of AS consuming individuals with those who did not consume AS and found that AS consuming people had different bacterial population in their intestine which correlated with markers of obesity and GI. When they fed AS to the volunteers, they showed increased blood glucose levels as well as altered intestinal bacteria in just four days.

These scientific evidences clearly indicate that consumption of AS is associated with increased GI, risk of obesity related metabolic disorders and these changes are not direct but by altering the bacterial community in the intestine. Thus, a caution regarding the excessive use of AS as food additive needs reassessment and in-depth study before being approved for use by general population

References:

1. http://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm397716.htm

2. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Nature. 2014 Sep 17. doi: 10.1038/nature13793

Diabetes - Prevention and Management by Awareness - Part 2

Continuing from the part-1 of this series where we learned the types of diabetes, how they develop and what are the risk factors (link below). In this part, 2nd and last in this series, we will learn how diabetes harms us, is it just the increased glucose or it means something else as well.

http://simplefiedscience.blogspot.in/2014/01/diabetes-prevention-and-management-by.html

Come to think of it, how diabetes harms our body is yet another area where general population is found misinformed and misguided. There is much more than sugar in the urine, sweating, trembling of hands and legs, and usual anxiety in diabetes. The increased glucose level in the blood creates havoc for the cells in our body. It deregulates the normal metabolism and function of the organs including liver, heart, kidney, eyes, brain, lungs, blood capillaries and their cells.

Even though our cells are being severely affected and damaged by increased sugar in the blood, we do not realize this until it is too late. Initially, in type 2 diabetes, with little increase in the blood sugar our body tries to adjust by increasing the insulin level. Slowly, it reaches a point where even several fold increase in insulin, hyper-insulinemia, is also not effective to down regulate glucose level. And because insulin also helps in increased fatty acid synthesis, cell growth and many other physiological role, the enhanced levels of insulin may expose the body to many other pathological conditions such as metabolic deregulation, obesity, heart diseases, cancer and so on.

Image curtesy: http://www.lef.org/

 

After a while insulin level tapers down leading to full-blown diabetes where there is no regulation of blood glucose, whatsoever. At this stage gluco-meter readings come more than 400mg/dL.

The vessels that carry the blood get affected first leading to macro- and micro-angiopathy including endothelial dysfunction, arteriosclerosis and angiogenesis, neuropathy leading to loss in sensation and nerve conduction, nephropathy leading to kidney failure, occulopathy such as diabetic retinopathy, glaucoma and cataract development in eye lens. Besides these, the frequent glucose up-regulation (hyperglycemia) and down-regulation (hypoglycemia) creates problem to the brain functioning leading to hallucinations, disorientation, depression and other problems.

Cartoon curtesy: oldsailor2007.blogspot.com

 

Although early diagnosis would lead to better management of the diabetes, being older or newer disease is not as important as how well or poorly it has been managed. Even if diabetes is diagnosed early, if not managed well with proper diet, exercise and healthy lifestyle, the patients suffer more mortality and morbidity.

To be a diabetes free society it is as much an individual problem as a social problem. Many epidemiological studies indicate that society plays greater role in how and which disease spreads in its people.

Image curtesy: (Diabetics Friends Society) http://youngleaders.idf.org/

 

If a society has good attitude towards healthy eating and living, and educational and awareness programs to educate its people, the individuals could benefit and protect themselves from many diseases, including diabetes.

Image Curtesy: www.h3daily.com/

 

What is good eating and living attitude? To recognize how much calorie one needs to stay active and fit, to know which food has roughly how much calories, to be aware that in the comfort and luxury seeking society physical activity is equally or rather highly important factor to stay well and free of diseases. Individual eating and living approach will have better effect on overall behavior of the society towards how it protects its people and tackles the lifestyle diseases such as obesity and diabetes.

 

Image curtesy:http://lankaspice.wordpress.com

Thus, next time when you see someone reacting to high glucose level in a random blood test in disbelief, anguish, anxiety, worry and other emotional expressions, you know what we must do as an individual and as a society!

Diabetes - Prevention and Management by Awareness - Part 1

Can you visualize the response of a ‘healthy’ person when he finds out in a random blood test that his blood glucose is elevated? It is initially disbelief, anguish, anxiety, worry and mix of many other emotional expressions! In a few days, however, many of these feelings and expression vanish except the few ones which appear and disappear depending upon family and peer pressure regarding consuming a particular type of food or not.

Image Curtesy: http://articles.timesofindia.indiatimes.com

This is as much concern we have about the condition that is called ‘diabetes’ and how we take care of our selves after becoming a patient of diabetes. The little knowledge or rather lack of it regarding the high glucose condition in blood and how to respond to it and regulate it makes many people prone to becoming diabetics besides the early diagnosis in random tests. In addition to high glucose level, one must notice the symptoms as well which indicate towards the diabetic condition, some of which are mentioned in the cartoon below.

Image Source:blog.sterileshoe. com

According to International Diabetes Federation’s ‘Diabetes Atlas’, there are 382 million people suffering from diabetes globally and this number is likely to increase to nearly 600 million by 2035, which is alarming. Initially, diabetes considered a disease of rich and affluent, but now 80% of patients presently live in poor – or – middle-income nations. China and India are on the top of the chart with 98 and 65 millions sufferers, respectively. Majority of the patients are from active work force between the ages 40-60 years.

Irony is that most of these cases are preventable and/or manageable. But the lack of right education, resources and awareness plays key role in increasing the incidence of diseases. Thus, knowledge of the disease and awareness about how to prevent or delay it or live with it subsequent to diagnosis is crucial factors in fighting with this global health menace.

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Diabetes (type 1, 2 or gestational), sugar or high glucose condition, by whatever names you may know it, the common factor is increased blood glucose level even though the causes may differ from person to person.

In type 1 diabetes, the pancreas does not secret insulin, a hormone that regulates the level of glucose in blood. In type 2 diabetes, either insulin is not secreted by pancreas or if secreted it fails to function due to various reasons, one of them being insulin resistance. Insulin resistance develops due to many reasons, and obesity is one of the reasons. The gestational diabetes is a specific condition where some women develop diabetes like condition during the third trimester of their pregnancy due to increase levels of estrogen hormone. Metabolically, hormones estrogen and insulin work in opposition to each other.

Gestational diabetes, although in many cases disappears after delivery, in few cases it remains and leads to type 2 diabetes. The relation ship between the two is however not very clearly known at present.

In all these cases the insulin is either not formed or is not functional, and thus is not able to control the glucose level. So main culprit here is insulin.

Image Source: medimoon.com

Insulin is a hormone that helps the body organs like liver, muscle and adipose tissue take up glucose from the blood after the meal. In a healthy person this is the way that carbohydrate we consume as food or drink is channeled to these organs where they are stored and utilized as and when needed by the body.

Diabetes develops from our careless lifestyle and food habits. As physical activities get narrowed down due to conveniences created by extraordinary technological advances in recent years, body’s energy requirement has drastically decreased. On the other hand our meals have become heavy, nutritious, rich in calorie and increased consumption of such food quickly makes us obese. 

Consumption of more food than the body requires for daily activities and maintenance, will lead to storage in body, which slowly but steadily results in obesity.

Image Source: cheftimothymoore.com

Obesity is an unhealthy state as has been proven scientifically. It creates a chronic inflammatory condition in the body which acts as breeding ground for many diseases such as cancer, asthma and cardiovascular diseases, and also creates conditions like insulin resistance, which leads to diabetes.

Thus, what we eat, how we eat, when we eat and how we utilized what we have eaten determine and plays important role in our health as well as diseases. Basically, we become what we consume as our food. Personal and social eating behaviors decidedly play role in what and how much we consume. People often end up eating in excess due to individual temptation as well as family and peer pressure. Tendency to convince the self or persuade the other that one day of splurge will not matter much often lead to overeating. One incidence of indiscipline in eating makes one prone to splurge often, which deteriorates the health and leads to obesity and disease development.     

Image Source: thesymptomofdiabetes.org

Although some people may be genetically predisposed to develop diabetes, but awareness and vigilant dietary habit can help delay the disease development and can certainly help manage the disease and prevent health deterioration.

Gut microbes linked with obesity and weight gain!

If you are obese and wondering how did you accumulated all that weight, well you could blame it to the bacteria living in your gut.

A new research has shown that inbred germ-free mice quickly gained weight when given gut bacteria derived from obese human twins than those mice which received gut bacteria from the lean twins. Scientists tested at least four such human twin pairs-derived gut microbes in the mice which all received the same kind and amount of the food.

Image curtsy: http://blog.fooducate.com/ 

The study suggests that the gut microbiota, which include plethora of microbes such as bacteria, fungi, archea living in the intestine, can affect the metabolism and thus weight gain.

Scientist know that humans and microbes live in close association with each other, so much so that in number our body harbors far more microbial cells, nearly 100 trillion, than our own cells, in the ratio of 1 to 10. Although these numbers may look frightening to a layman but they actually live in a mutually beneficial relations with our body.

Some of them live as commensals - living but not causing any harm, symbiotic –mutually helping each other and some of them may live as pathogens, causing harm such as well known pathogenic diseases.

It is therefore logical that if so many organisms are in or on us, they may also affect how we function as an organism, they should then also affect our metabolism, so to say.

And they do! It is known that any disturbances in our intestinal environment could lead to the growth of harmful microbes which may lead to chronic inflammatory diseases including obesity, metabolic disorders and infections.

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Scientist have shown earlier that an antibiotic-resistant gut bacteria, Clostridium difficile, known to affect and killing thousands in America, can be treated by transplanting microbiota from a healthy individual into an infected persons gut.

Scientists have also shown that the gut microbes also amend our immune system which helps us identify the foreign pathogens, antigens and harmful substances and eradicate them. The increasing cases of allergic and autoimmune disease in the developed countries are arguably believed to be related with disturbance in microbial habitat, our body, due to the hygienic living, leading to emergence of “hygiene hypothesis” to explain these increased incidences.

Previously, scientists have also experimentally shown that when the intestinal flora of the lean mice was given to the obese mice, they successfully controlled and decreased the body weight in obese mice. 

The study led by Jeffrey I. Gordon at Washington University in St. Louis, MO found that when mice with the lean microbiota were made to cohabitate with mice having obese microbiota much before they gained weight, and found that the populations of bacteria in the obese-type mice changed to those of their lean cage-mates, and that their weight did not increase as well. It is known that mice eat each other’s faeces, so this allowed the replacement of ‘obese’ microbiota, but this migration was unidirectional and microbiota from obese mice did not colonize in the lean mice gut.

Image Curtsy: www.vaccinationnews.com

However, interestingly enough, scientist also discovered that besides this there is strong correlation between the diet we take and how the gut microbes behave. When the researchers fed the mice a low fat diet rich in fruit and vegetables, the gut microbes from lean mice migrated to those with the obese type. But, when a high-fat diet low in fruits and vegetable was fed to mice, the microbe transfer did not occur and obese-type mice went on to gain weight.

This and many other studies clearly indicate that our relationship with the microbes is very intricate and scientists are unraveling these intricacies slowly but steadily. However, a lot remains to be learnt about various other players including genetics, environment, diet and diseases in the interaction of microbes and our body which benefits as well as harm each other.