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.

  

Dad's Liver Fibrosis May Protect Son’s Liver

The liver is a vital organ in our body which performs many important functions, but sometimes gets inflamed because of various reasons including virus infection, and alcohol and drug abuse. A chronic inflammation of the liver results in fibrosis wherein healthy liver cells are replaced by collagen loaded fibrotic cells which compromise the structure and function of the liver. This course of disease is known for many years now, and there is nothing new in this.

source: www.hivandhepatitis.com

What is new however is that scientists have now discovered that fibrosis in father’s liver somehow results in the protection from this disease in his sons. The chronic liver injury because of either viral infection or alcohol abuse induces an epigenetic change in the sperm’s DNA. When this changed DNA is transmitted to the next generation it would protect the male progeny from liver fibrosis.

Epigenetic changes are modifications in the DNA caused by non-genetic and mostly lifestyle related exposures in ones’ life time. Although these changes do not seems to last and have limited effects on long-term evolutionary changes, sometimes epigenetic changes in the germ cells such as sperm can be transmitted to the next generation. Epigenetic changes are now implicated in many present day diseases including cancer and diabetes.  

The scientists, Müjdat Zeybel and his colleagues, reported that a long history of liver damage in rodents was related with transfer of adaptive epigenetic changes that suppressed liver fibrosis in first and 2^nd generation male rats.

The scientists induced liver fibrosis in rats by two different methods using carbon tetra-chloride and bile duct ligation. They found that prolonged lung injury resulted in the changes in rat sperm DNA which were inherited by the progeny. The male rats born from those sperms when tested by giving similar insults showed increased protection from liver fibrosis.

The main reason for this protection is higher amounts of a factor that prevent liver fibrosis, called peroxisome proliferator-activated receptor-gamma (PPAR-γ) in scientific term, in the liver of male pups that inherited modified DNA. They also had lower amounts of fibrosis promoting growth factor called Transforming growth factor-beta1, compared to those that inherited normal DNA.

The study published in Nature thus suggests that a history of liver fibrosis in male can protect their male progeny from such disease in next generation. But this protective adaptation was limited to liver and was not found to protect other organs, for example kidney, from fibrosis.

Although it remains to be determined how applicable these findings are in humans, this report should not result in believing that paternal liver injury would protect against the alcohol abuse-related liver diseases. We must therefore resist temptation to run to the bar with the logic to give protection to our future sons because many other genetic and environmental components are involved in liver diseases.