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1H NMR-based metabolomic study on resistance to diet-induced obesity in AHNAK knock-out mice.

Abstract：

:AHNAK is a giant protein of approximately 700 kDa identified in human neuroblastomas and skin epithelial cells. Recently, we found that AHNAK knock-out (AHNAK(-/-)) mice have a strong resistance to high-fat diet-induced obesity. In this study, we applied (1)H NMR-based metabolomics with multivariate statistical analysis to compare the altered metabolic patterns detected in urine from high-fat diet (HFD) fed wild-type and AHNAK(-/-) mice and investigate the mechanisms underlying the resistance to high-fat diet-induced obesity in AHNAK(-/-) mice. In global profiling, principal components analysis showed a clear separation between the chow diet and HFD groups; wild-type and AHNAK(-/-) mice were more distinctly separated in the HFD group compared to the chow diet group. Based on target profiling, the urinary metabolites of HFD-fed AHNAK(-/-) mice gave higher levels of methionine, putrescine, tartrate, urocanate, sucrose, glucose, threonine, and 3-hydroxyisovalerate. Furthermore, two-way ANOVAs indicated that diet type, genetic type, and their interaction (gene × diet) affect the metabolite changes differently. Most metabolites were affected by diet type, and putrescine, threonine, urocanate, and tartrate were also affected by genetic type. In addition, cis-aconitate, succinate, glycine, histidine, methylamine (MA), phenylacetylglycine (PAG), methionine, putrescine, uroconate, and tartrate showed interaction effects. Through the pattern changes in urinary metabolites of HFD-fed AHNAK(-/-) mice, our data suggest that the strong resistance to HFD-induced obesity in AHNAK(-/-) mice comes from perturbations of amino acids, such as methionine, putrescine, threonine, and histidine, which are related to fat metabolism. The changes in metabolites affected by microflora such as PAG and MA were also observed. In addition, resistance to obesity in HFD-fed AHNAK(-/-) mice was not related to an activated tricarboxylic acid cycle. These findings demonstrate that (1)H NMR-based metabolic profiling of urine is suitable for elucidating possible biological pathways perturbed by functional loss of AHNAK on HFD feeding and could elucidate the mechanism underlying the resistance to high-fat diet-induced obesity in AHNAK(-/-) mice.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kim IY,Jung J,Jang M,Ahn YG,Shin JH,Choi JW,Sohn MR,Shin SM,Kang DG,Lee HS,Bae YS,Ryu DH,Seong JK,Hwang GS

doi

10.1016/j.bbrc.2010.11.048

subject

Has Abstract

pub_date

2010-12-17 00:00:00

pages

428-34

issue

3-4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(10)02107-8

journal_volume

403

pub_type

杂志文章

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1H NMR-based metabolomic study on resistance to diet-induced obesity in AHNAK knock-out mice.