Metabolic Response Of Mice Research Articles

Thermal Treatment of Commercial Sweetener Solutions Modulates the Metabolic Responses in C57BL/6 Mice during a 24-Week-Long Exposition

The purpose of this paper was to evaluate the effect of thermal treatment (TT: 121 ± 2 °C, 15 min) on the composition of commercial sweeteners diluted in water (10 °Brix). Additionally, we evaluated the impact of this TT on metabolic responses in C57BL/6 mice during a 24-week treatment. The sweeteners included in this study were sucrose (SC), glucose-63 (GLU63), agave syrup (AS), sucralose (SUC), and steviol glycosides (STG). HPLC analysis showed changes in the concentration of simple sugars of GLU63 and AS after TT. Importantly, in all sweeteners, TT modulated metabolic responses in mice. The mice drinking thermally treated sweetener solution showed an increase of 10–13% (p < 0.05) in food intake (AS, SUC, and STG), beverage intake (2–21%; SC and GLU63), weight gain (38%; SUC), energy (10–13%; AS, SUC, and STG), glucose levels (11–17%; SC and STG), GLP-1 (30%; SC) and insulin (88%; AS) release, and the generation of protein carbonyl (SC) and malondialdehyde (all sweeteners tested) compared to mice drinking solution without TT. In conclusion, TT of sweetener solutions accentuates the metabolic responses of healthy mice, which can be related to overweight and its comorbidities.

Differential Strain-dependent Ovarian and Metabolic Responses in a Mouse Model of PCOS.

Several mouse models have been developed to study polycystic ovarian syndrome (PCOS), a leading cause of infertility in women. Treatment of mice with DHT for 90 days causes ovarian and metabolic phenotypes similar to women with PCOS. We used this 90-day DHT treatment paradigm to investigate the variable incidence and heterogeneity in 2 inbred mouse strains, NOD/ShiLtJ and 129S1/SvlmJ. NOD mice naturally develop type 1 diabetes, and recent meta-analysis found increased androgen excess and PCOS in women with type 1 diabetes. The 129S1 mice are commonly used in genetic manipulations. Both NOD and 129S1 DHT-treated mice had early vaginal opening, increased anogenital distance, and altered estrus cycles compared with control animals. Additionally, both NOD and 129S1 mice had reduced numbers of corpora lutea after DHT exposure, whereas NOD mice had decreased numbers of preantral follicles and 129S1 mice had reduced numbers of small antral follicles. NOD mice had increased body weight, decreased white adipocyte size, and improved glucose sensitivity in response to DHT, whereas 129S1 mice had increased body weight and white adipocyte size. NOD mice had increased expression of Adiponectin, Cidea, Srebp1a, and Srebp1b and 129S1 mice had decreased Pparg in the white adipose tissues, whereas both NOD and 129S1 mice had increased expression of Glut4 and Prdm16, suggesting DHT may differentially affect glucose transport, thermogenesis, and lipid storage in white adipose tissue. DHT causes different ovarian and metabolic responses in NOD and 129S1 mice, suggesting that strain differences may allow further elucidation of genetic contributions to PCOS.

Enantioselectivity effects of imazethapyr enantiomers to metabolic responses in mice

Imazethapyr (IMZT) is a typical chiral pesticide with two enantiomers with the R-IMZT having the main herbicidal activity. However, the enantioselectivity of the effects of IMZT enantiomers on human and animals is still unclear. In this study, a nuclear magnetic resonance (NMR)-based metabolomics method and determination of oxidative stress were used to evaluate the enantioselectivity of IMZT enantiomers in mice. The results showed that the R-IMZT caused larger disturbances of endogenous metabolites and the S-IMZT had stronger interferences to oxidation defense system. The significantly perturbed metabolic pathways in mice exposed to the R-enantiomer were the valine, leucine and isoleucine biosynthesis pathway as well as the phenylalanine, tyrosine and tryptophan biosynthesis pathway. However, exposure of mice to the S-enantiomer did not significantly affect the metabolic pathways, but exposure led to an increase of catalase (CAT) activity and an increase in malondialdehyde (MDA) content in the liver. These results indicate that we need to conduct a more comprehensive assessment of the health risks of pesticide monomers in the future. In a word, these results provide more evidence for assessing the differences in health risks of IMZT enantiomers to mammals as well as provide more references for the promotion and use of pesticide monomers in the future.

Evaluating Metabolic Responses in Mice to Nanosized Titanium Dioxide Particles Using Gas Chromatography- Mass Spectrometry Based Metabolomics

Evaluating Metabolic Responses in Mice to Nanosized Titanium Dioxide Particles Using Gas Chromatography- Mass Spectrometry Based Metabolomics

Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators

To systemically identify long noncoding RNAs (lncRNAs) regulating energy metabolism, we performed transcriptome analyses to simultaneously profile mRNAs and lncRNAs in key metabolic organs in mice under pathophysiologically representative metabolic conditions. Of 4,759 regulated lncRNAs, function-oriented filters yield 359 tissue-specifically regulated and metabolically sensitive lncRNAs that are predicted by lncRNA-mRNA correlation analyses to function in diverse aspects of energy metabolism. Specific regulations of liver metabolically sensitive lncRNAs (lncLMS) by nutrients, metabolic hormones, and key transcription factors were further defined inprimary hepatocytes. Combining genome-wide screens, bioinformatics function predictions, and cell-based analyses, we developed an integrative roadmap to identify lncRNA metabolic regulators. An lncLMS was experimentally confirmed in mice to suppress lipogenesis by forming a negative feedback loop in the SREBP1c pathway. Taken together, this study supports that a class of lncRNAs function as important metabolic regulators and establishes a framework for systemically investigating the role of lncRNAs in physiological homeostasis.

ISH NIA PS 01-01 Ghrelin receptor in the endothelial cells regulates blood pressure and metabolic responses in mice

ISH NIA PS 01-01 Ghrelin receptor in the endothelial cells regulates blood pressure and metabolic responses in mice

Disparate Metabolic Responses in Mice Fed a High-Fat Diet Supplemented with Maize-Derived Non-Digestible Feruloylated Oligo- and Polysaccharides Are Linked to Changes in the Gut Microbiota.

Studies have suggested links between colonic fermentation of dietary fibers and improved metabolic health. The objectives of this study were to determine if non-digestible feruloylated oligo- and polysaccharides (FOPS), a maize-derived dietary fiber, could counteract the deleterious effects of high-fat (HF) feeding in mice and explore if metabolic benefits were linked to the gut microbiota. C57BL/6J mice (n = 8/group) were fed a low-fat (LF; 10 kcal% fat), HF (62 kcal% fat), or HF diet supplemented with FOPS (5%, w/w). Pronounced differences in FOPS responsiveness were observed: four mice experienced cecal enlargement and enhanced short chain fatty acid production, indicating increased cecal fermentation (F-FOPS). Only these mice displayed improvements in glucose metabolism compared with HF-fed mice. Blooms in the gut microbial genera Blautia and Akkermansia were observed in three of the F-FOPS mice; these shifts were associated with reductions in body and adipose tissue weights compared with the HF-fed control mice. No improvements in metabolic markers or weights were detected in the four mice whose gut microbiota did not respond to FOPS. These findings demonstrate that FOPS-induced improvements in weight gain and metabolic health in mice depended on the ability of an individual’s microbiota to ferment FOPS.

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice.

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

Comparing systemic metabolic responses in mice to single or dual infection with Plasmodium berghei and Heligmosomoides bakeri.

Concomitant infections with Plasmodium and gastrointestinal nematodes are frequently observed in humans. At the metabolic level, the cross-talk between the host and multiple coexisting pathogens is poorly characterized. The purpose of this study was to give a comprehensive insight into the systemic metabolic phenotype of mice with a single or dual infection with Plasmodium berghei and Heligmosomoides bakeri. Four groups of eight NMRI female mice were infected with P. berghei or H. bakeri, or with both species concurrently. An additional group remained uninfected, and served as control. Mice were sacrificed at day 19 of the experiment. We collected samples from the liver, spleen, kidney, three intestinal regions, and four brain regions. All biological samples were subjected to (1)H nuclear magnetic resonance spectroscopy, combined with multivariate data analysis, to establish metabolic fingerprints of each tissue from the various infection groups. Compared to uninfected mice, single and dual species infection models showed unique metabolic profiles. P. berghei exerted major effects on glycolysis, tricarboxylic acid cycle, and nucleotide and amino acid metabolism in all studied tissues with the exception of the gut. H. bakeri was characterized by a dysregulation of choline and lipid metabolism in most tissues examined with a particularly strong imprint in the jejunum. Simultaneous co-infection with P. berghei and H. bakeri induced the strongest and most diverse effects in the liver and spleen but led to only minor changes in the intestinal and cerebral parts assessed. Infection with P. berghei showed more pronounced and systemic alterations in the mice metabolic profile than H. bakeri infection. The metabolic fingerprints in the co-infection models were driven by P. berghei infection, whilst the presence of H. bakeri in co-infections had little effect. However, simultaneous co-infection showed indeed the least metabolic disruptions in the peripheral tissues, namely the gut and brain.

Abstract 173: Modulation of the Metabolic Effects of Leptin by the Brain Renin-Angiotensin System

Genetic deletion or delivery of antagonists of the renin-angiotensin system (RAS) directly to the brain abolishes both renal and adipose sympathetic nervous activity (SNA) responses to leptin, suggesting a cross-talk between these central cardiovascular / metabolic control systems. To further explore this mechanism of cross-talk, we examined the sensitivity of metabolic responses in mice with transgenic hyperactivity of the brain RAS (“sRA” mice) to acute leptin treatment. sRA mice, previously shown to exhibit hypertension, polydipsia, and elevated SNA and resting metabolic rate, exhibit brain-specific RAS hyperactivity through neuronal expression of human renin via the synapsin promoter and expression of human angiotensinogen via its own promoter. When housed at standard room temperature (23°C), twice-daily leptin injections (1 mg/kg, i.p., 3 hrs into light phase and 2 hrs preceding dark phase of a 12:12-hr cycle) caused significant and similar reductions in body mass (control -0.76±0.13, n=5 male; sRA -0.65±0.09 g/d, n=5 male, P=0.46) and food intake (-1.43±0.69 vs -1.99±0.27 kcal/d, P=0.63) in littermate control and sRA mice. When housed at thermoneutrality (30°C) in an OxyMax (Columbus Instruments) CLAMS apparatus, leptin injections had minimal effects on total daily food intake in control mice (from 7.4±0.6 at baseline to 8.1±0.5 kcal/d with leptin, n=4 male + 4 female, P=0.29), but reduced food intake in sRA mice (from 8.3±0.7 to 6.0±0.4 kcal/d, n=4 male + 4 female, P=0.003). sRA mice were more sensitive to leptin’s suppressive effect on physical activity (control from 998±148 to 655±90, P=0.10; sRA from 1232±304 to 588±41 counts/d, P=0.005). Unexpectedly, leptin had a suppressive effect upon metabolic rate in sRA mice (control from 16.4±1.3 to 16.8±0.9, P=0.44; sRA from 20.2±1.1 to 17.5±0.9 kcal/kg lean/hr, P<0.001). Together, these data support a cross-talk between the brain RAS and leptin signaling in the control of metabolic function. These data suggest a complex and context-dependent mechanism of interaction between leptin and brain angiotensin, with gross alterations in leptin-induced food, physical activity, and metabolic rate responses when tested in a thermoneutral environment.

The metabonomics of combined dietary exposure to phthalates and polychlorinated biphenyls in mice

Humans undergo simultaneous daily exposure to a multitude of endocrine-disrupting compounds (EDCs). In present study, after combined exposure to endocrine disruptors DEHP and Aroclor 1254 for 12 days, a liquid chromatography/time-of-flight mass spectrometer method combining both reversed-phase (RP) and hydrophilic interaction chromatography (HILIC) separations was carried out to investigate the metabolic responses in mice. The metabolic profiles of endogenous metabolites could differentiate the dose and control groups in both RPLC and HILIC modes. Moreover, the male mice and female mice in different groups could be obviously clustered in their own regions with combined model. Fourteen lysoPCs, PC(18:4/18:1), lysoPE(18:2/0:0), phenylalanine and tryptophan were identified as potential biomarkers for the combined toxicity of DEHP and Aroclor 1254. Different change trends could be observed for the identified lysoPCs, due to their different levels of uptake and metabolism in mice. Moreover, gender-specific differences in several lysoPCs (e.g. lysoPC(18:0), lysoPC(22:6), lysoPC(20:3), and PC(18:4/18:1)) were observed for treated mice. The metabonomic results indicated the combined exposure led to a disturbance of lipid metabolism. The mRNA expressions of PLA2, ACOX1, CPT1, FAS and SCD1 involved in lipid metabolism were investigated. Among them, significant increases of FAS and SCD1 expressions in the liver induced by the exposure could be observed for both male and female mice, contributing to the hepatic lipid accumulation in mice. Besides lipid metabolism, tryptophan metabolism and phenylalanine metabolism may also be involved with the toxic responses to these EDCs. The present study not only improves the understanding of the combined toxicity of phthalates and PCBs but also shows that the metabonomic approach may prove to be a promising technique for the toxicity research of EDCs.

W1856 Neurokinin-1receptor (NK-1r) Deficiency is Associated With Reduced Weight Gain and Improved Glucose Metabolic Responses in Mice

W1856 Neurokinin-1receptor (NK-1r) Deficiency is Associated With Reduced Weight Gain and Improved Glucose Metabolic Responses in Mice