Newswise — Rockville, Md. (September 8, 2020)—New research in mice suggests a protein found predominately in white blood cells helps keep gastrointestinal bacteria in balance and may protect against metabolic disorders. The study is published in Physiological Genomics. It was chosen as an APSselect article for September.
Lipocalin 2 is a protein found in white blood cells and functions as part of the immune system. In response to inflammation and metabolic stress, the body produces more lipocalin 2, primarily in the liver and in fat (adipose) tissue. The protein is a biomarker for intestinal inflammation and metabolic syndrome—a group of conditions, such as high blood pressure and high blood sugar, that increase the risk of heart disease, diabetes and stroke. Lipocalin 2 has been found to accumulate in people with obesity, which may either worsen or dampen chronic inflammation.
Whether lipocalin 2 is beneficial or detrimental in metabolic syndrome is unclear in the scientific literature. While some research suggests lipocalin 2 is indicative of metabolic syndrome, other studies have shown that excess lipocalin 2 in adipose tissue maintains glucose tolerance, lowers cholesterol and prevents fat from accumulating in the liver.
A link also exists between metabolic syndrome, inflammation and the bacterial colonies in the intestinal tract (gut microbiota). An imbalance of the different bacteria in the gut can lead to inflammation and insulin resistance. Intriguingly, a previous study from the same research group found that mice deficient of lipocalin 2 have an imbalance in gut bacteria. However, less is known about whether the role of lipocalin 2 in metabolic syndrome could be linked to the gut microbiota.
Researchers studied groups of mice with and without lipocalin 2. The research team measured body weight, blood sugar, triglyceride and cholesterol levels when the mice were 3, 6 and 9 months old. Weight gain and increase in body fat was comparable between the lipocalin 2-deficient and control groups at 3 months old. However, the deficient group showed an early increase in triglycerides, which is a major predictor of metabolic syndrome. As the mice aged, the deficient group gained more weight and body fat and also had higher blood sugar and insulin levels compared with the control group. “Collectively, these data demonstrate that [lipocalin 2] deficiency induces metabolic syndrome profoundly in aged mice,” the researchers wrote.
In addition, the older mice without lipocalin 2 had changes in their gut microbiota consistent with “leaky gut syndrome,” a condition in which bacteria and toxins seep out of the intestinal tract into nearby tissues. Leaky gut syndrome can lead to inflammation and an increased risk of obesity and metabolic syndrome. A lipocalin 2 deficiency “could cause a reprogramming toward an obesogenic [gut microbiota], which would increase susceptibility to metabolic disorders,” the researchers explained.
“Overall, the current study demonstrates that [lipocalin 2] is necessary in maintaining gut bacterial homeostasis, which reduces the risk of metabolic disease,” the research team wrote.
Read the full article, “Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice,” published in Physiological Genomics. It is highlighted as one of this month’s “best of the best” as part of the American Physiological Society’s APSselect program. Read all of this month’s selected research articles.
NOTE TO JOURNALISTS: To schedule an interview with a member of the research team, please contact the APS Communications Office or call 301.634.7314. Find more research highlights in our Newsroom.
Physiology is a broad area of scientific inquiry that focuses on how molecules, cells, tissues and organs function in health and disease. The American Physiological Society connects a global, multidisciplinary community of more than 10,000 biomedical scientists and educators as part of its mission to advance scientific discovery, understand life and improve health. The Society drives collaboration and spotlights scientific discoveries through its 16 scholarly journals and programming that support researchers and educators in their work.
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