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Review
. 2016 Nov 22;21(11):1596.
doi: 10.3390/molecules21111596.

4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity

Anaguiven Avalos-Soriano  1 , Ricardo De la Cruz-Cordero  2 , Jorge L Rosado  3 , Teresa Garcia-Gasca  4
Affiliations
Review

4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity

Anaguiven Avalos-Soriano et al. Molecules. .

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)-κB. 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.

Keywords: 4-hydroxyisoleucine; Trigonella foenum-graecum; fenugreek; insulinotropic.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Adipocyte hypertrophy and systemic alterations. Adipocyte hypertrophy leads to chronic inflammation, insulin resistance (IR), and lipotoxicity. The increased flux of free fatty acid (FFA) to nonadipose tissues results in lipid accumulation, lipoapoptosis, and organ dysfunction.
Figure 2
Figure 2
The branched-chain amino acid (2S,3R,4S)-4-hydroxyisoleucine.
Figure 3
Figure 3
Insulinotropic effects of 4-hydroxyisoleucine in the pancreas, skeletal muscle, adipose tissue and liver. 4-OHIle increases insulin secretion and improves insulin sensitivity in nonadipose tissues.
See this image and copyright information in PMC

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