Working with a national team of researchers, a scientist from the Florida campus of The Scripps Research Institute has shown for the first time a link between low levels of a specific hormone and increased risk of metabolic disease in humans.
The study, published online ahead of print in The Journal of Clinical Endocrinology & Metabolism, focuses on the hormone adropin, which was previously identified by Scripps Research Associate Professor Andrew Butler's laboratory during an investigation of obese and insulin-resistant mice. Adropin is believed to play an important role in regulating glucose levels and fatty acid metabolism.
"The results of this clinical study suggest that low levels of adropin may be a factor increasing risk for developing metabolic disorders associated with obesity and insulin resistance, which could then lead to diseases such as type 2 diabetes," said Butler, who led the new study with Peter J. Havel, professor of molecular biosciences and nutrition at the University of California, Davis.
Approximately 47 million adults in the United States have metabolic syndrome, according to the American College of Cardiology. The National Institutes of Health defines metabolic syndrome as a group of risk factors, especially obesity and insulin resistance, that occur together and increase the risk for coronary artery disease, stroke, and type 2 diabetes.
In the new study, which involved 85 women and 45 men, Butler and his colleagues showed that obesity is associated with lower adropin levels. Lower adropin levels were also observed in individuals with a higher "metabolic syndrome risk factor" score, a score determined by measuring triglycerides, LDL cholesterol, HDL, glucose, blood pressure, and waist circumference.
The scientists also observed circulating adropin concentrations increased significantly at three and six months following gastric bypass surgery in morbidly obese patients. Interestingly, adropin levels returned to pre-surgical levels at 12 months after surgery.
Another surprising finding of the new study was that in people of normal weight, women had lower plasma adropin levels than men. In addition, obesity had a bigger negative effect on adropin levels in men. Interestingly, obesity in woman was also not associated with lower plasma adropin levels. The significance of the differences between men and woman is unknown at the moment.
"But the link between low levels of adropin and increased metabolic risk was observed in both sexes," Butler said. "The impact is there, irrespective of gender."
Adropin levels were also found in general to decrease with age—the decline was highest in those over 30 years of age. As with obesity, the aging effect appeared to be more pronounced in men.
Findings in Humans Mirror Preclinical Work
The new study is an important extension of earlier pre-clinical studies using animal models published in the July edition of Obesity. In that study, Butler and colleagues deleted the gene encoding adropin from mice. The scientists found that, while normal in appearance, adropin-deficient mice have insulin resistance and, when fed diets with a high fat content, develop a more severe impaired glucose tolerance (IGT). These findings suggest reduced insulin production and attenuated response to insulin, which are the defining features of type 2 diabetes. Importantly, mice having only one functional copy of the gene encoding adropin also exhibited increased propensity for developing impaired glucose tolerance with obesity. These findings provided important pre-clinical evidence evidence that low levels of adropin are associated with increased risk of developing type 2 diabetes.
In other studies, Butler's laboratory observed that obese mice exhibit dramatic reductions in circulating adropin levels, and that insulin resistance was reversed after injections with a synthetic form of adropin.
"The data from these studies provide strong evidence suggesting that low levels of adropin may be an indicator of risk for insulin resistance in obesity and, consequently, an increased risk for metabolic diseases, including type 2 diabetes," Butler said. "We see a lot of similarity between animal model data and the new human data—low adropin levels in humans are associated with a host of metabolic syndrome risk factors normally associated with obesity and insulin resistance."
Taken together, these studies suggest the possibility that therapeutics designed to boost the supply of adropin might be useful in fighting obesity and metabolic disease.
In addition to Butler and Havel, authors of the study, "Low Circulating Adropin Concentrations With Obesity And Aging Correlate With Risk Factors For Metabolic Disease And Increase After Gastric Bypass Surgery In Humans," include Charmaine S. Tam and Eric Ravussin of Louisiana State University, Baton Rouge; Kimber L. Stanhope and Mohamed R. Ali of the University of California, Davis; Bruce M. Wolfe of the Oregon Health Sciences University, Portland; and Majella O'Keeffe and Marie-Pierre St Onge of Columbia University.
The study was supported by the National Institutes of Health (award numbers HL061352, DK060412, HL075675, HL09133, UL1 RR024156-03, UL1 RR024146, and 1P30 DK072476-06); the American Diabetes Association; The Novo Nordisk Diabetes Innovation Award Program; the University of California, Davis Health Care Systems Award; the Irving Center for Translational Science; and the Pennington Biomedical Research Center's Nutrition Obesity Research Center program.
Eric Sauter | EurekAlert!
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
18.07.2018 | Life Sciences
18.07.2018 | Materials Sciences
18.07.2018 | Health and Medicine