Leptin Resistance: A Possible Interface Between Obesity and Pulmonary-Related Disorders.
BACKGROUND
Under normal physiological conditions, leptin regulates body weight by creating a balance between food intake and energy expenditure. However, in obesity, serum leptin levels increase and become defective to retain energy balance.


METHODS
Elevated serum leptin levels are regarded as an established marker of obesity. It is also reported that obese asthmatic patients have maximum serum leptin levels compared to other groups such as non-obese asthmatics, and normal obese and non obese subjects without asthma. In addition to having an appetite suppressing effect, leptin also regulates certain acute-phase protein expressions including α-1 antitrypsin (A1AT) in the liver.


RESULTS
A1AT is a protease inhibitor that counterbalances the activity of the neutrophil elastase (NE) enzyme. A1AT reductions in obese-leptin resistant subjects lead to increased NE activity. The overactivity of NE degrades lung tissue proteins, which may lead to pulmonary disorders including asthma.


CONCLUSIONS
On the basis of prior studies, it could be hypothesized that, in obese asthmatic patients, the highest degree of leptin failure/resistance might lead to the creation of an imbalance between NE and its inhibitor A1AT. To ascertain this, large scale prospective studies are warranted to assess the comparative serum leptin and A1AT levels and NE activity in asthmatic non-obese and obese patients, simultaneously. Such studies might help to devise novel interventional therapies for the treatment of pulmonary-related problems including asthma, chronic obstructive pulmonary disorder (COPD), and other lung defects in susceptible obese subjects in the future.
Diabetes and Cardio-Metabolic Disorders Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan; Obesity and Diabetes Research Laboratory, Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan.
Abdul
A
Rehman Khan
Diabetes and Cardio-Metabolic Disorders Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
Fazli Rabbi
FR
Awan
Asthma; Chronic Obstructive Pulmonary Disorder (COPD); Leptin Resistance; Neutrophil Elastase (NE); Obesity; α-1 Antitrypsin (A1AT)