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

Anaguiven Avalos-Soriano,Jorge Rosado,Ricardo De La Cruz-Cordero,Teresa Garcia-Gasca

doi:10.3390/molecules21111596

Anaguiven Avalos-Soriano, Jorge Rosado + Show 2 more

Open Access

https://doi.org/10.3390/molecules21111596

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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.

Highlights

Obesity is an adverse health condition characterised by increased accumulation of body fat [1], which increases the risk of noncommunicable diseases and, in turn, can lead to death
Health Organization (WHO) declared obesity a global epidemic in 1997 and considers it to be the most preventable disease, principally because most obese patients benefit from changing their dietary habits and lifestyle [2]
Adipocyte hypertrophy leads to chronic inflammation, insulin resistance (IR), and lipotoxicity

Summary

Introduction

Obesity is an adverse health condition characterised by increased accumulation of body fat [1], which increases the risk of noncommunicable diseases and, in turn, can lead to death. In obese individuals, adipose tissue shows chronic activation of proinflammatory signalling pathways, including Jun N-terminal kinase (JNK) and nuclear factor κB (NF-κB) [13,14]. The origin of these inflammatory mediators is hypertrophic adipose tissue. The decreased ability of peripheral tissues to respond to insulin leads to systemic alterations that affect both adipose and nonadipose tissues, including chronic inflammation and macrophage infiltration. Triglyceride levels must remain within a very narrow range in nonadipose cells; when adipose tissue systematically releases large amounts of FFAs, the increased storage of triglycerides together with IR lead to cell death, toxic effects, and impairment of the functions of nonadipose tissues.

Adipocyte hypertrophy and systemic

Experimental results

Insulinotropic effects of

Conclusions