Metabolomic profiling of urinary changes in mice with monosodium glutamate-induced obesity

Abstract

Obesity with related complications represents a widespread health problem. The etiopathogenesis of obesity is often studied using numerous rodent models. The mouse model of monosodium glutamate (MSG)-induced obesity was exploited as a model of obesity combined with insulin resistance. The aim of this work was to characterize the metabolic status of MSG mice by NMR-based metabolomics in combination with relevant biochemical and hormonal parameters. NMR analysis of urine at 2, 6, and 9 months revealed altered metabolism of nicotinamide and polyamines, attenuated excretion of major urinary proteins, increased levels of phenylacetylglycine and allantoin, and decreased concentrations of methylamine in urine of MSG-treated mice. Altered levels of creatine, citrate, succinate, and acetate were observed at 2 months of age and approached the values of control mice with aging. The development of obesity and insulin resistance in 6-month-old MSG mice was also accompanied by decreased mRNA expressions of adiponectin, lipogenetic and lipolytic enzymes and peroxisome proliferator-activated receptor-gamma in fat while mRNA expressions of lipogenetic enzymes in the liver were enhanced. At the age of 9 months, biochemical parameters of MSG mice were normalized to the values of the controls. This fact pointed to a limited predictive value of biochemical data up to age of 6 months as NMR metabolomics confirmed altered urine metabolic composition even at 9 months.

Impaired nicotinamide adenine dinucleotide (NAD+) metabolism in diabetes and diabetic tissues: Implications for nicotinamide‐related compound treatment

“…Consistent with our hypothesis, nicotinamide catabolites are known to be increased by type 2 diabetes in both rodent models and humans 89 . In addition, a recent report showed that C57BL/6 mice fed with a high-fat diet had a two-to threefold increase in 2-PY and 4-PY, as compared with mice fed a normal chow diet, and those levels were significantly reduced by treatment with metformin + vildagliptin (dipeptidyl peptidase inhibitor) 145 , also attesting our hypothesis. It is known that both NAD + salvage activity 146 and nicotinamide catabolites 147 show diurnal variations as a result of circadian rhythm.…”

Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity

“…Two weeks of treatment with analogs 1 and 2 significantly decreased urinary concentrations of MNA and its oxidation products 2-PY and 4-PY compared with the untreated high fat diet-fed group. An increase in these metabolites was previously reported to be associated with obesity in a mouse model of DIO [ 25 ], as well as in a model of chemically induced obesity [ 39 ] and in genetically obese db/db mice [ 40 ]. An increase in the urinary levels of MNA metabolites indicates peroxisome proliferation [ 41 , 42 ], which is related to inflammation, obesity and metabolic syndrome [ 43 , 44 ].…”

“…A statistically significant increase in hexanoylglycine and unassigned acids, collectively referred to as SCFA derivatives, was observed after treatment with analogs 1 and 3, and this finding is in agreement with our previous studies. A reduction in the concentrations of these metabolites was detected in urine from mice with chemically induced obesity [ 39 ]. The low levels of SCFA derivatives in urine from mice with DIO increased after anti-diabetic therapy with metformin, vildagliptin and a combination of the two [ 15 ], as well as after subcutaneous treatment with liraglutide (unpublished results).…”

Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury

“…Similar to other studies that showed allantoin as a sensitive marker of oxidative stress [39–41], we also show here that AII/R injury results in high levels of allantoin at both ischemia times. Methylamine is a product of gut bacteria metabolising dietary choline and it is lowered upon alterations in gut microbiota composition [42–44]. It is therefore not surprising that after 60 min of ischemia, the levels of methyalamines drops and level of choline increases in our model.…”