Studies by researchers at the Karolinska Institutet in Sweden, and the University of Oxford in the U.K., suggest that the amino acid glutamine could help people with obesity reduce inflammation of fat tissue and reduce fat mass. Their investigations also showed how glutamine levels altered gene expression in different cell types.

The scientists acknowledge that more research will be needed before glutamine supplements might be considered as a treatment for obesity, but the results are promising, suggested Mikael Ryden, MD, PhD, professor and senior physician at the department of medicine in Huddinge, Karolinska Institutet. “Our study shows that glutamine is anti-inflammatory in the fat tissue by changing the gene expression in several different cell types,” said Ryden. “This means that a lack of glutamine, which may occur during long-term obesity, could lead to epigenetic changes that fuel inflammation in the body … Our results suggest that treatment with glutamine could be of value against obesity and insulin resistance.” Ryden is corresponding author of the team’s published paper in Cell Metabolism, which is titled, “Glutamine Links Obesity to Inflammation in Human White Adipose Tissue.”

When we consume more calories than our bodies need, the extra energy is stored as triglycerides in white adipose tissue (WAT), the authors explained. “Excess WAT mass leads to increased fat cell size (hypertrophy) and a chronic low-grade inflammation.” These changes in WAT are implicated in metabolic disorders such as insulin resistance, type 2 diabetes (T2D), and cardiovascular disease. What isn’t yet known is what causes the inflammation.

The Karolinska Institutet team and their collaborators queried whether the cause may be linked with changes in fat tissue metabolism. “We hypothesized that the local metabolic environment could be an important determinant,” they wrote. To investigate this in more detail, the investigators assessed how metabolic processes differed in fat tissue collected from the abdomens of 52 obese and 29 non-obese women. They found that of the six metabolites that displayed highly significant differences between samples from obese, and non-obese individuals, glutamine stood out as the one that displayed the largest difference and highest significance level. People with obesity had on average lower levels of glutamine in their fat tissue than normal weight people. Lower glutamine levels were also associated with larger fat cell size and higher body fat percentage, independently of body mass index (BMI). “… attenuated glutamine levels in WAT associate with increased fat mass and fat cell size,” the team wrote.

Mikael Ryden, MD, PhD, professor and senior physician at the department of medicine, Huddinge, Karolinska Institutet. [Ulf Sirborn]
Glutamine is an amino acid that is involved in many critical functions, such as providing energy and maintaining intestinal health. It also has anti-inflammatory effects on, for example, immune system white blood cells and T cells. “Glutamine is conditionally essential and the most abundant amino acid in the body,” the investigators stated. Through a combination of studies in human and mouse WAT, and in human adipocytes and live animals, the researchers demonstrated that glutamine levels influenced the expression of different genes. The results indicated that low glutamine levels induced an increase in the expression of pro-inflammatory genes in the fat tissue.

In vivo experiments showed that obese mice receiving glutamine injections for two weeks had less fat tissue inflammation than control mice given saline injections. Body fat mass, fat cell volume, and blood glucose levels were also reduced in the glutamine-treated animals. And in an analysis of cultured human fat cells, both the expression of proinflammatory genes and lipid content were reduced after incubation with increasing concentrations of glutamine. The largest effect was observed after treatment with 5–20 millimolar (mM) glutamine for 11 days.

The researchers also studied the effects of changing glutamine levels in fat cells. They found that glutamine impacts O-GlcNAcylation, a mechanism that can control epigenetic changes. People with obesity had higher levels of O-GlcNAcylation in their fat tissue, while mice and human cells treated with glutamine had lower levels of O-GlcNAcylation in the cell nucleus. “At least in adipocytes, reduced glutamine levels result in increased UDP-GlcNAc levels and O-GlcNAcylation of chromatin-binding proteins located near inflammatory genes,” they wrote.

The authors noted potential limitations of their study, and said that further research will be needed to investigate the effects and safety of glutamine administration. “We know, however, that glutamine is also important for cell division and the metabolism of cancer and therefore, more research on possible long-term side effects is needed before glutamine may be recommended as a dietary supplement to help treat obesity and its complications,” Ryden said. “Future studies are needed to understand the dynamics of this immunometabolic crosstalk and its potential therapeutic impact,” the authors concluded. Even so, they noted. “Altogether, glutamine may alleviate adipose inflammation and improve fat tissue function in obesity and T2D.”

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