Breaking News
February 20, 2019 - Study sheds new light on how antibiotic resistance genes are transferred between bacteria
February 20, 2019 - Chronic Wasting Disease may soon spread to humans, warns CDC
February 20, 2019 - Scientists identify new genetic causes linked to abnormal pregnancies and miscarriages
February 20, 2019 - Using LyoSpeed technology to avoid residual solvent when drying HPLC fractions
February 20, 2019 - New screening tool more likely to identify sexual and labor exploitation of youth
February 20, 2019 - Newly licensed nurses work for long hours, also have a second paid job
February 20, 2019 - Physicists identify simple mechanism used by deadly bacteria to fend off antibiotics
February 20, 2019 - FDA Grants Priority Review to Genentech’s Personalized Medicine Entrectinib
February 20, 2019 - Exposure to chemicals before and after birth is associated with a decrease in lung function
February 20, 2019 - Neuroscientists reveal that simple brain region can guide complex feats of mental activity
February 20, 2019 - Study finds new link between food allergies and multiple sclerosis
February 20, 2019 - First gene therapy operation for macular degeneration is a success
February 20, 2019 - Physicians graduated outside the U.S. offer better care for Medicare patients with complex needs
February 20, 2019 - FDA Approves Keytruda (pembrolizumab) for the Adjuvant Treatment of Patients with Melanoma with Involvement of Lymph Node(s) Following Complete Resection
February 20, 2019 - Study identifies brain cells that modulate behavioral response to threats
February 20, 2019 - Researchers take closer look at how viruses bind cells and cause infection
February 20, 2019 - Newly developed gene therapy helps decelerate aging process
February 20, 2019 - Study suggests new treatment strategy for deadly brain cancer
February 20, 2019 - Scientists develop unique hybrid implant that imitates bone structure
February 20, 2019 - Push-ups can be tailored to meet specific needs of individuals
February 20, 2019 - Early-career job loss has long term health implications
February 20, 2019 - CVD Does Not Modify Depression-Mortality Link in Elderly
February 20, 2019 - Electrical activity early in fruit flies’ brain development could shed light on how neurons wire the brain
February 20, 2019 - Machine learning technique helps predict which asthma patients respond to corticosteroid therapy
February 20, 2019 - Self-reported sleep duration is a useful tool to measure sleep in children, study suggests
February 20, 2019 - T-cells play key role in how the body fights follicular lymphoma
February 20, 2019 - Study shows how 3D organization of genetic material helps perpetuate the species
February 20, 2019 - Researchers engineer stem cell with ‘suicide genes’ to induce cell death in all but beta cells
February 20, 2019 - Study reveals major sex differences in management of cardiovascular risk factors among U.S. adults
February 20, 2019 - Health Tip: Get Your Child to School on Time
February 20, 2019 - Shortcut strategy for screening compounds with clinical potentials for drug development
February 20, 2019 - Common acid reflux drugs tied to elevated risk for kidney disease
February 20, 2019 - Microbiome could be culprit when good drugs do harm
February 20, 2019 - Prenatal exposure to forest fires causes stunted growth in children
February 20, 2019 - Gene therapy restores hearing in mice with congenital genetic deafness
February 20, 2019 - First molecular test predicts treatment response for kidney cancer
February 20, 2019 - New method for improved visualization of single-cell RNA- sequencing data
February 20, 2019 - Researchers capture altered brain activity patterns of Parkinson’s in mice
February 20, 2019 - A possible blood test for detecting Alzheimer’s disease before symptoms show
February 20, 2019 - Primary care physicians associated with longevity, new research finds
February 19, 2019 - New study identifies many key lessons to establish sanctioned safe consumption sites
February 19, 2019 - Single CRISPR treatment can safely and stably correct genetic disease
February 19, 2019 - Multinational initiative to study familial primary distal renal tubular acidosis
February 19, 2019 - Breakthrough study highlights the promise of cell therapies for muscular dystrophy
February 19, 2019 - Subsymptom Threshold Exercise Speeds Concussion Recovery
February 19, 2019 - Midline venous catheters – infants: MedlinePlus Medical Encyclopedia
February 19, 2019 - Searching for side effects
February 19, 2019 - Humanity is all right, probably, although human extinction remains quite possible, researcher says
February 19, 2019 - Having Anesthesia Once as a Baby Does Not Cause Learning Disabilities, New Research Shows
February 19, 2019 - Anti-cancer immunotherapy could be used to fight HIV
February 19, 2019 - Customized Micropatterning for Improved Physiological Relevance
February 19, 2019 - Unique gene therapy approach paves new way to tackle rare, inherited diseases
February 19, 2019 - Activating gene that helps excite neurons reverses depression in male mice
February 19, 2019 - Science Puzzling Out Differences in Gut Bacteria Around the World
February 19, 2019 - Cells that destroy the intestine
February 19, 2019 - On recovery, vulnerability and ritual: An exhibit in white
February 19, 2019 - Scientific Duo Gets Back To Basics To Make Childbirth Safer
February 19, 2019 - COPD patients need more support when understanding new chest symptoms
February 19, 2019 - Using light-based method for production of pharmaceutical molecules
February 19, 2019 - Scientists find link between inflammation and cancer
February 19, 2019 - The High Cost Of Sex: Insurers Often Don’t Pay For Drugs To Treat Problems
February 19, 2019 - Hearing impairment associated with accelerated cognitive decline with age
February 19, 2019 - Researchers identify multiple genetic variants associated with body fat distribution
February 19, 2019 - Influenza and common cold are completely different diseases, study shows
February 19, 2019 - Scientists untangle how microbes manufacture key antibiotic compound
February 19, 2019 - Greater primary care physician supply associated with longer life spans
February 19, 2019 - HIV-1 protein suppresses immune response more broadly than thought
February 19, 2019 - Brain imaging indicates potential success of drug therapy in depressive patients
February 19, 2019 - For 2020 Dem Hopefuls, ‘Medicare-For-All’ Is A Defining Issue, However They Define It
February 19, 2019 - Specialized lung cells appear in the developing fetus much earlier than previously thought
February 19, 2019 - KU professor discusses promise of brain-computer interface to aid, restore communication
February 19, 2019 - Highly effective solution for detecting onset of aggregation in nanoparticles
February 19, 2019 - Early marker of cardiac damage triggered by cancer treatment identified
February 19, 2019 - Antidepressant drug could save people from deadly sepsis, research suggests
February 19, 2019 - CRISPR technology creates pluripotent stem cells that are ‘invisible’ to the immune system
February 19, 2019 - New study establishes how stress favors breast cancer growth and spread
February 19, 2019 - Midlife Systemic Inflammation Linked to Later Cognitive Decline
February 19, 2019 - Therapy derived from parasitic worms downregulates proinflammatory pathways
February 19, 2019 - Antimicrobial reusable coffee cups are less likely to become contaminated with bacteria, study shows
February 19, 2019 - Harnessing the evolutionary games played by cancer cells to advance therapies
Nasal delivery of weight-loss hormone eases breathing problems in sleeping mice

Nasal delivery of weight-loss hormone eases breathing problems in sleeping mice

image_pdfDownload PDFimage_print

Experimenting with mice, Johns Hopkins Medicine researchers have added to evidence that a hormone best known for helping regulate hunger and body weight might also ease breathing problems experienced during sleep more effectively when given through the nose.

Although clinical trials using the hormone, known as leptin, aren’t yet on the horizon, the investigators say their success delivering it through the test animals’ noses may help them develop easier-to-use therapies for people with sleep-related breathing problems such as sleep apnea.

The findings were published online Oct. 12 in the American Journal of Respiratory and Critical Care Medicine.

Leptin, a hormone made by fat cells that was first identified in 1994, targets the brain’s appetite center, helping to regulate appetite. “Although leptin’s potential for treating obesity and curbing overeating failed to materialize in human trials, its role in the respiratory system has triggered new rounds of therapeutic possibilities,” says Vsevolod Polotsky, M.D., Ph.D., professor of pulmonary and critical care medicine at the Johns Hopkins University School of Medicine, and senior author of the study. His laboratory has been studying the hormone for more than 20 years.

A particular focus of his research is the search for new strategies to treat obstructive sleep apnea, a serious and even potentially lethal condition that affects approximately 30 percent of U.S. adults, Polotsky says. The prevalence increases to 50 percent among obese populations. The disorder is marked by frequent, brief periods when breathing stops during sleep due to upper airways closing. The result is oxygen deprivation. People with obesity are also at higher than usual risk of another sleep breathing problem called obesity hypoventilation syndrome, in which brain centers that regulate breathing during sleep operate abnormally and fail to increase breathing appropriately in response to carbon dioxide, which results in the buildup of carbon dioxide in the blood. The syndrome often accompanies sleep apnea.

Currently, the most common effective treatment for these sleep problems is regularly wearing a continuous positive airway pressure (CPAP) mask and machine, which mechanically increases air pressure in the throat to keep airways open during sleep. But because CPAP machines must be worn at all times during sleep and some patients find them cumbersome, uncomfortable, noisy and confining, substantial numbers of people cannot tolerate them and stop their use.

Polotsky says previous research has shown that leptin is essential in regulating breathing, and can successfully treat sleep-disordered breathing symptoms in obese mice lacking leptin. However, mice with diet-induced obesity are resistant to the leptin hormone and failed to respond when leptin was injected into the belly (or abdomen).

“One major reason for leptin-resistance is that it is hard for injected hormone to get through the blood-brain barrier and into the target brain cells,” says Slava Berger, a postdoctoral fellow in Polotsky’s lab and the first author of the paper. “We suspected that administering leptin through the nose might circumvent that barrier and overcome leptin-resistance in our test animals.”

To test that idea, the researchers first made adult male mice obese by feeding them a high-fat diet for 16 weeks. Since leptin can cause weight loss in the long term—which also reduces breathing problems —the researchers first assessed the immediate effect of a single dose of leptin (0.4 milligrams per kilogram of body weight) on sleep breathing before the weight-loss effect could take place. In both mice receiving leptin and those not receiving it?either squirted in the nose or injected in the belly?the researchers compared how much air mice inhaled, measured by changes in temperature, and the number of times mice experienced inadequate oxygen during sleep. They looked at blood oxygen levels by putting neck collars on mice, which were similar to the clips used on human fingers in urgent care settings to measure blood oxygen levels. The results indicated that only mice given leptin through the nose showed increased ventilation by over 40 percent during sleep, which alleviated upper airway obstruction and cut the number of times the mice had insufficient oxygen levels by more than half.

The researchers stained neurons from the brains of mice given leptin through the nose and found that the leptin receptor on the surface of the neurons had detected leptin, meaning this method of delivery bypassed the blood-brain barrier and transported leptin directly to the brain, thus avoiding leptin-resistance.

To further look at the longer term metabolic effects of leptin treatment, researchers treated a subset of their obese mice with leptin through the nose or the abdomen for two weeks. Again, only mice treated with leptin through the nose showed reduction in food intake and weight loss. Those mice lost 1 gram, almost 3 percent of total body weight, while the mice given leptin in the abdomen gained more than 3 grams, indicating leptin resistance.

“We believe our study provides the first evidence of its kind that giving leptin through the nose eases sleep disordered breathing,” says Polotsky. “In the future, we plan studies to look at the effects of different doses of leptin administered through the nose in mice.”

“Identifying key molecules that regulate breathing and how these molecules could be used to treat medical conditions such as sleep apnea is a significant achievement,” said Michael Twery, Ph.D., Director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. “The discovery sets the stage on which new treatment options can be developed.”

The researchers caution that, as was the case with leptin’s use to treat obesity, mouse studies may not be applicable to humans. “We believe that leptin treatment should be tested in humans at some point, but we first need to look into the potential side effects, allergic reactions and other factors before that can happen,” says Polotsky.

Costs, too, are a consideration for future therapies. According to the American Sleep Association, an average CPAP costs $500-$3,000. The current clinical use of leptin in the form of metreleptin—an extremely expensive synthetic replacement for leptin—treats rare cases of leptin deficiency at hundreds of thousands of dollars per year. However, Polotsky and Berger estimate that if nasal leptin is found safe and effective for clinical use, costs could be similar to inhaled forms of the hormone insulin, which runs about $25 per vial.


Explore further:
Leptin tied to sleep quality in obese patients with T2DM

Journal reference:
American Journal of Respiratory and Critical Care Medicine

Provided by:
Johns Hopkins University School of Medicine

Tagged with:

About author

Related Articles