Scientists uncover a stunning connection between metabolism and immunity

The picture shows the expression of NUCB2 in immune cells. NUCB2 is a gene that controls inflammation in obesity.

While searching for treatments for obesity, scientists recently discovered a gene called nucleobindin-2 (Nucb2) that was believed to play a role in satiety. However, in a new study published in Cell Reports, Yale researchers discovered an unexpected role for the gene in reducing inflammation.

To better understand the role of Nucb2, a research team led by Vishwa Deep Dixit, Waldemar Von Zedtwitz Professor of Comparative Medicine and Professor of Immunobiology, examined the gene – and the protein it codes for – in cells and in several Mouse models. They deleted the gene first from the whole animal, then specifically from neurons, fat cells and immune cells. When they removed the gene from immune cells known as macrophages and fed the mice on a high-fat diet, the macrophages produced inflammation, which in turn caused insulin resistance in the animals that lacked Nucb2. Insulin resistance can be caused by obesity and is a precursor to diabetes.

The results suggest that Nucb2 does not play a role in the feeling of satiety, but has a key role in the immune system. “Our study clarifies the physiological function of Nucb2,” said Dixit. “It has nothing to do with eating. Its main function is to control inflammation by regulating macrophage activation in adipose tissue. “Future studies should further investigate how inflammation, immunity, and metabolism are related, and whether drug therapy can target Nucb2 to reduce insulin resistance in obesity,” Dixit said.

The other authors are Anthony Ravussin, Yun-Hee Youm, Jil Sander, Seungjin Ryu, Kim Nguyen, Luis Varela, Gerald I. Shulman, Sviatoslav Sidorov, Tamas L. Horvath and Joachim L. Schultze. The study was supported in part by the National Institutes of Health and the Glenn Foundation.

Publication: Anthony Ravussin et al., “Loss of nucleobindin-2 causes insulin resistance in obesity without affecting satiety or obesity,” Cell Reports, 2018; DOI: 10.1016 / j.celrep.2018.06.112

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