title: 4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity.
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.
authors.affiliation: Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Juriquilla, Querétaro, Qro. 76230, Mexico. anaguiven@hotmail.com.
authors.forename: Anaguiven
authors.initials: A
authors.lastname: Avalos-Soriano
authors.affiliation: Nucitec S.A. de C.V. Querétaro, Qro. 76215, Mexico. rdelacruz@nucitec.com.
authors.forename: Ricardo
authors.initials: R
authors.lastname: De la Cruz-Cordero
authors.affiliation: Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Juriquilla, Querétaro, Qro. 76230, Mexico. jlrosado@prodigy.net.mx.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Rosado
authors.affiliation: Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Juriquilla, Querétaro, Qro. 76230, Mexico. tggasca@uaq.edu.mx.
authors.forename: Teresa
authors.initials: T
authors.lastname: Garcia-Gasca
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007333:Insulin Resistance; D007532:Isoleucine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008111:Liver Function Tests; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D029910:Trigonella / Q000737:chemistry*
chemical_list: C104672:4-hydroxyisoleucine; D010936:Plant Extracts; D007532:Isoleucine; D005947:Glucose
keywords: 4-hydroxyisoleucine; Trigonella foenum-graecum; fenugreek; insulinotropic