The Science

What is glycerol-3-phosphate phosphatase (G3PP)?

Our scientists recently identified a novel enzyme that lies at the heart of glucose and lipid metabolism named glycerol 3-phosphate phosphatase. G3PP directly converts glycerol-3-phosphate, a by-product of glucose metabolism, into glycerol, thus limiting the amount of sugar available to form fat deposits and the formation of toxic reactive oxygen species (ROS). We collected multiple evidence that G3PP controls glycolysis, lipogenesis, lipolysis, fatty acid oxidation, cellular redox, and mitochondrial energy metabolism in β-cells and hepatocytes, as well as glucose-induced insulin secretion. The data indicate that G3PP is a key player in metabolic regulation and is an entirely novel target with much potential for cardiometabolic disorders.

G3PP activators to counteract overnutrition

We have shown that overexpression of G3PP in rat liver lowers hepatic glucose production from glycerol and plasma triglycerides and reduces fat deposits in hepatocytes. Furthermore, G3PP overexpression elevates plasma HDL and reduces LDL levels. NIMIUM Therapeutics is developing activators of G3PP to counteract the toxic effects of overnutrition as G3PP appears to act as a glucose excess detoxification machine.

G3PP activation to promote healthy aging

Cardiometabolic diseases constitute a major global health challenge. These disorders also contribute to aging-related conditions and geriatric disabilities. Our research, using C. elegans , shows that enhancing G3PP activity promotes healthy aging in these animals and protect from various stresses. This is a particularly interesting avenue of research as aging is a significant risk factor for all cardiometabolic disorders and the WHO has declared 2021-2030 the Decade of Healthy Ageing.

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