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Differential Effect of Non-Purified and Semi-Purified Standard Diets on Kynurenine and Peripheral Metabolites in Male C57BL/6J Mice.

ABSTRACT: The kynurenine (Kyn) pathway plays crucial roles in several inflammation-induced disorders such as depression. In this study, we measured Kyn and other related molecules in the blood plasma, brain, and urine of male C57BL/6J mice (B6) fed non-purified (MF) and semi-purified (AIN-93G and AIN-93M) standard rodent diets. Mice fed MF had increased plasma Kyn levels compared with those on AIN93-based diets, as well as decreased hippocampal Kyn levels compared with those fed AIN-93G. Previous studies showed that branched chain amino acids (BCAAs) suppress peripheral blood Kyn transportation to the brain, but plasma BCAA levels were not significantly different between the diet groups in our study. Urine metabolome analysis revealed that feed ingredients affected the excretion of many metabolites, and MF-fed mice had elevated excretion of kynurenic and quinolinic acids, pivotal metabolites in the Kyn pathway. Collectively, the level of critical metabolites in the Kyn pathway in the central and peripheral tissues was strongly affected by feed ingredients. Therefore, feed selection is a critical factor to ensure the reproducibility of experimental data in studies involving rodent models.

SUBMITTER: Yajima Y

PROVIDER: S-EPMC8733355 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Differential Effect of Non-Purified and Semi-Purified Standard Diets on Kynurenine and Peripheral Metabolites in Male C57BL/6J Mice.

Yajima Yuhei Y Okuno Alato A Nakamura Isamu I Miyazaki Teruo T Honda Akira A Toyoda Atsushi A

International journal of tryptophan research : IJTR 20220104

The kynurenine (Kyn) pathway plays crucial roles in several inflammation-induced disorders such as depression. In this study, we measured Kyn and other related molecules in the blood plasma, brain, and urine of male C57BL/6J mice (B6) fed non-purified (MF) and semi-purified (AIN-93G and AIN-93M) standard rodent diets. Mice fed MF had increased plasma Kyn levels compared with those on AIN93-based diets, as well as decreased hippocampal Kyn levels compared with those fed AIN-93G. Previous studies ...[more]

PMID: 35002254

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Project description:BackgroundIn recent years, much attention has been given to the lack of reproducibility in biomedical research, particularly in preclinical animal studies. This is a problem that also plagues the alcohol research field, particularly in consistent consumption in animal models of alcohol use disorders. One often overlooked factor that could affect reproducibility is the maintenance diet used in preclinical studies.MethodsHerein, 2 well-established models of alcohol consumption, the "drinking in the dark" (DID) procedure and the continuous 2-bottle choice (C2BC) paradigm, were employed to determine the effects of diet on ethanol (EtOH) consumption. Male C57BL/6J mice were given 1 of 6 standard rodent chow diets obtained from Purina LabDiet(®) , Inc. (Prolab(®) RMH 3000) or Harlan(®) Laboratories, Inc. (Teklad Diets T.2916, T.2918, T.2920X, T.7912, or T.8940). A separate group of animals were used to test dietary effects on EtOH pharmacokinetics and behavioral measures following intraperitoneal (IP) injections of various doses of EtOH.ResultsMice eating Harlan diets T.2916 (H2916) and T.2920X (H2920) consumed significantly less EtOH and exhibited lower blood EtOH concentrations (BECs) during DID; however, during C2BC, animals maintained on Harlan T.7912 (H7912) consumed more EtOH and had a higher EtOH preference than the other diet groups. EtOH consumption levels did not stem from changes in alcohol pharmacokinetics, as a separate group of animals administered EtOH IP showed no difference in BECs. However, animals on Harlan diet T.2920X (H2920) were more sensitive to alcohol-induced locomotor activity in an open-field task. No diet-dependent differences were seen in alcohol-induced sedation as measured with loss of righting reflex.ConclusionsAlthough these data do not identify a specific mechanism, together, they clearly show that the maintenance diet impacts EtOH consumption. It is incumbent upon the research community to consider the importance of describing nutritional information in methods, which may help decrease interlaboratory reproducibility issues.

Project description:BACKGROUND:Adverse effects of high-fat diets (HFD) on metabolic homeostasis are linked to adipose tissue dysfunction. The goal of this study was to examine the effect of the HFD nature on adipose tissue activity, metabolic disturbances and glucose homeostasis alterations in male mice compared with female mice. METHODS:C57BL/6J mice were fed either a chow diet or HFD including vegetal (VD) or animal (AD) fat. Body weight, plasmatic parameters and adipose tissue mRNA expression levels of key genes were evaluated after 20 weeks of HFD feeding. RESULTS:HFD-fed mice were significantly heavier than control at the end of the protocol. Greater abdominal visceral fat accumulation was observed in mice fed with AD compared to those fed a chow diet or VD. Correlated with weight gain, leptin levels in systemic circulation were increased in HFD-fed mice in both sexes with a significant higher level in AD group compared to VD group. Circulating adiponectin levels as well as adipose tissue mRNA expression levels were significantly decreased in HFD-fed male mice. Although its plasma levels remained unchanged in females, adiponectin mRNA levels were significantly reduced in adipose tissue of both HFD-fed groups with a more marked decrease in AD group compared to VD group. Only HFD-fed male mice were diabetic with increased fasting glycaemia. On the other hand, insulin levels were only increased in AD-fed group in both sexes associated with increased resistin levels. VD did not induce any apparent metabolic alteration in females despite the increased weight gain. Peroxisome Proliferator-Activated Receptors gamma-2 (PPAR?2) and estrogen receptor alpha (ER?) mRNA expression levels in adipose tissue were decreased up to 70% in HFD-fed mice but were more markedly reduced in male mice as compared with female mice. CONCLUSIONS:The nature of dietary fat determines the extent of metabolic alterations reflected in adipocytes through modifications in the pattern of adipokines secretion and modulation of key genes mRNA expression. Compared with males, female mice demonstrate higher capacity in controlling glucose homeostasis in response to 20 weeks HFD feeding. Our data suggest gender specific interactions between the diet's fatty acid source, the adipocyte-secreted proteins and metabolic disorders.

Project description:The importance of the kynurenine pathway in normal immune system function has led to an appreciation of its possible contribution to autoimmune disorders such as rheumatoid arthritis. Indoleamine-2,3-dioxygenase (IDO) activity exerts a protective function, limiting the severity of experimental arthritis, whereas deletion or inhibition exacerbates the symptoms. Other chronic disorder with an inflammatory component, such as atherosclerosis, are also suppressed by IDO activity. It is suggested that this overall anti-inflammatory activity is mediated by a change in the relative production or activity of Th17 and regulatory T cell populations. Kynurenines may play an anti-inflammatory role also in CNS disorders such as Huntington's disease, Alzheimer's disease and multiple sclerosis, in which signs of inflammation and neurodegeneration are involved. The possibility is discussed that in Huntington's disease kynurenines interact with other anti-inflammatory molecules such as Human Lymphocyte Antigen-G which may be relevant in other disorders. Kynurenine involvement may account for the protection afforded to animals with cerebral malaria and trypanosomiasis when they are treated with an inhibitor of kynurenine-3-monoxygenase (KMO). There is some evidence that changes in IL-10 may contribute to this protection and the relationship between kynurenines and IL-10 in arthritis and other inflammatory conditions should be explored. In addition, metabolites of kynurenine downstream of KMO, such as anthranilic acid and 3-hydroxy-anthranilic acid can influence inflammation, and the ratio of these compounds is a valuable biomarker of inflammatory status although the underlying molecular mechanisms of the changes require clarification. Hence it is essential that more effort be expended to identify their sites of action as potential targets for drug development. Finally, we discuss increasing awareness of the epigenetic regulation of IDO, for example by DNA methylation, a phenomenon which may explain differences between individuals in their susceptibility to arthritis and other inflammatory disorders.

Dataset Information

Differential Effect of Non-Purified and Semi-Purified Standard Diets on Kynurenine and Peripheral Metabolites in Male C57BL/6J Mice.

Publications

Differential Effect of Non-Purified and Semi-Purified Standard Diets on Kynurenine and Peripheral Metabolites in Male C57BL/6J Mice.

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