Abstract: Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek (Trigonella foenum-graecum) seeds, exhibits interesting effects on IR related to obesity. 4-OHIle increases glucose-induced insulin release, and the insulin response mediated by 4-OHIle depends on glucose concentration. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-KB. Here, we present a review of the research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle in in vitro and in vivo models.
Conclusion : The peculiar nonprotein branched amino acid 4-hydroxyisoleucine has been described as an efficient compound in the regulation of insulin secretion. Due to the fact that it acts as an insulin secretagogue in the presence of elevated blood glucose concentrations, it has been proposed for the potential treatment of insulin resistance, diabetes and obesity. The beneficial effects observed are related to the regulation of blood glucose, the reduction of lipotoxicity by decreasing plasma triglycerides, FFAs, and total cholesterol, and the improvement of liver function. The mechanism of action is related to a reduced activation of JNK and NF-KB activity. 4-OHIe has demonstrated unique therapeutic potential against insulin resistance and the harmful effects associated with inadequate glucose uptake, lipotoxicity, and liver dysfunction, which ultimately cause diabetes, one of the major pandemic diseases worldwide.
Keywords: 4-hydroxyisoleucine; Trigonella foenum-graecum; insulinotropic; fenugreek
4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity, Anaguiven Avalos-Soriano, Ricardo De la Cruz-Cordero, Jorge L. Rosado and Teresa Garcia-Gasca, Molecules 2016, 21, 1596