Amino acids stimulate Akt phosphorylation, and reduce IL-8 production and NF-κB activity in HepG2 liver cells.
Hepatic insulin resistance and inflammatory cytokine production contribute to the manifestation of the metabolic syndrome. As amino acids have been implicated in modulating insulin signaling and inflammation, we have investigated the effects of glutamine, leucine and proline on markers of inflammation and insulin sensitivity in HepG2 liver cells. Cells were incubated with IL-1β (5 ng/mL) to stimulate IL-8 production. After 24 h, glutamine inhibited IL-8 production significantly (p<0.05) at 2, 5 and 10 mM (to 82, 73 and 72% of control), whereas leucine reduced IL-8 production significantly only at 10 mM (66%) and proline at 5 and 10 mM (71 and 52%). Glutamine, leucine and proline all reduced NF-κB activity after 3 h of IL-1β stimulation at 2, 5 and 10 mM (p<0.001). Insulin-induced (1 nM) Akt phosphorylation was reduced in cells treated with tumour necrosis factor-α (10 ng/mL) for 24 h, but was partly restored by simultaneous incubation with glutamine, leucine and proline (25 mM). Phosphorylation of glycogen synthase kinase-3β was unaffected by insulin stimulation and amino acid treatment. Our results indicate that glutamine, leucine and proline attenuate IL-8 production, probably through inhibition of NF-κB, and that they increase Akt phosphorylation in HepG2 cells.
Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands. L.vanMeijl@hb.unimaas.nl
Leonie E C
LE
van Meijl
Herman E
HE
Popeijus
Ronald P
RP
Mensink
D005973:Glutamine / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C508606:CXCL8 protein, human; D007328:Insulin; D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D011392:Proline; D051057:Proto-Oncogene Proteins c-akt; D007930:Leucine