Diabetic mice with low levels of the amino acid serine have an increased risk for peripheral neuropathy, according to a new study in Nature. When given serine in their diets, the mice experienced relief from their neuropathy.

The study highlights the crucial role non-essential amino acids play in nervous system health, paving the way for potential neuropathy treatments in humans.

“We were surprised that dialing up and down a non-essential amino acid had such a profound effect on metabolism and diabetic complications,” says senior author Christian Metallo, a professor in Salk’s Molecular and Cell Biology Laboratory. “It just goes to show that what we think of as dogma can change under different circumstances, such as in disease conditions.”

Study Details

Researchers wanted to know if a chronic deficiency of serine triggers peripheral neuropathy. To test this hypothesis, scientists fed mice a serine-free diet combined with either a low-fat or high-fat diet for 12 months. A control group was also part of the study. According to the research team, a low-serine, high-fat diet speeds up the development of peripheral neuropathy in diabetic mice. Serine supplements, on the other hand, helped delay the development of diabetic neuropathy in those same diabetic mice. Previous research has linked serine deficiency with neurodegenerative disorders, say the study authors.

Serine-rich foods include soybeans, nuts, eggs, chickpeas, lentils, meat, and fish. The study authors caution that more research is needed to determine how serine supplements fit into a possible treatment plan for peripheral neuropathy.

“Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy,” wrote the authors.

“We were surprised that dialing up and down a non-essential amino acid had such a profound effect on metabolism and diabetic complications…”

Conclusion

“Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.”