Researchers Identify Novel Adipokine Linked to Chronic Inflammation

An international team of scientists led by Andreas F. H. Pfeiffer and Natalia Rudovich of the German Institute of Human Nutrition (DIfE), a partner in the DZD, has identified a novel adipokine secreted by fat cells into the blood, which may promote insulin resistance* and chronic inflammation in obese individuals, and thus may lead to diabetes and vascular diseases. The new findings may contribute in the future to developing alternative approaches to treat obesity-related diseases. The DZD researchers have now published their findings in the journal Diabetes (Murahovschi, V. et al., 2014).

The number of obese individuals has increased significantly in the last three decades** throughout the world. According to the World Health Organization, today more deaths are associated with too-high rather than with too-low body weight. The research findings of recent years show that obesity and the associated metabolic syndrome*** increase the risk of type 2 diabetes, certain types of cancer and cardiovascular diseases. According to the latest research, chronic inflammatory reactions are causally involved in the development of these complications. The molecular mechanisms leading to these obesity-related inflammatory processes, however, are still largely unexplored.
The team led by the two physicians Dr. Rudovich and Dr. Pfeiffer has now identified the protein molecule Wingless-type signaling pathway protein-1 (WISP1) as another possible link between obesity and chronic inflammatory responses and/or insulin resistance. Previous studies had thus far associated the molecule only with the regulation of bone growth and the development of some types of cancer.
As the researchers now show for the first time based on clinical studies, the visceral fat tissue, which is located in the abdomen around the intestines, produces a large quantity of WISP1, which it secretes into the blood. The amount of protein synthesis is closely related to the degree of insulin resistance and the release of specific inflammation markers. By contrast, the subcutaneous fat tissue produces only moderate quantities of this protein molecule. Moreover, the physicians noticed that after weight loss, the WISP1 content in the blood of the study participants decreased. In addition, depending on the dose, the protein stimulates the differentiation of the cultured human macrophages**** into the classic M1 type, which plays a role in many acute inflammatory diseases. “We suspect that WISP1 could be one of the substances that regulate macrophage function and migration into the fat tissue,” said Veronica Murahovschi, first author of the study.
“The more we learn about the molecular mechanisms underlying obesity-related inflammatory processes, the easier it will be to develop suitable drugs in the future which counteract diseases such as diabetes, heart attack or stroke,” said Pfeiffer, who heads the Department of Clinical Nutrition at the DIfE. “For instance, drugs to specifically reduce the increased release of inflammatory mediators such as WISP1 to a normal level would be conceivable,” said Rudovich. “However, it is a long way from basic research to an applicable therapeutic drug. Nevertheless, the results already help to better understand the relationships between obesity, the immune system and metabolic diseases.”


Link to journal article

Background Information:
* The term “insulin resistance” refers to a reduced response of body cells to the hormone insulin. It mainly applies to muscle and liver cells, but also to fat cells. Insulin resistance is the precursor to type 2 diabetes.
** Marie Ng et al. (2014), The Lancet 384:766-781
*** The metabolic syndrome is a combination of obesity, high blood pressure, insulin resistance of the body cells and a disturbed lipid metabolism.
**** Phagocytes (macrophages) are cells of the immune system. They develop from monocytes and are quantitatively the largest group of inflammatory cells in adipose tissue. Macrophages can differentiate into various subsets of macrophage types, which perform very different functions. M1 macrophages play a role in many acute inflammatory diseases. M2 macrophages, by contrast, inhibit inflammation.