The Influence of Dietary Restriction, Germ-Free Status, and Aging on Adrenal Catecholamines in Lobund-Wistar Rats

Dietary calorie restriction (CR) delays age-related physiologic changes, increases maximum life span, and reduces cancer incidence. Here, we present the novel finding that chronic reduction of dietary calories by 50% without changing the intake of dietary protein induced the activity of mouse hepatic carbamyl phosphate synthetase I (CpsI) 5-fold. In liver, CpsI protein, mRNA, and gene transcription were each stimulated by ϳ3-fold. Thus, CR increased both the rate of gene transcription and the specific activity of the enzyme. Short-term feeding studies demonstrated that higher cpsI expression was due to CR and not consumption of more dietary protein. Intestinal CpsI activity was stimulated 2-fold, while its mRNA level did not change, suggesting enzyme activity or translation efficiency was stimulated. CpsI catalyzes the conversion of metabolic ammonia to carbamyl phosphate, the rate-limiting step in urea biosynthesis. cpsI induction suggests there is a shift in the metabolism of calorie-restricted animals toward protein catabolism. CpsI induction likely facilitates metabolic detoxification of ammonia, a strong neurotoxin. Enhanced protein turnover and metabolic detoxification may extend life span. Physiologic similarities between calorie-restricted and hibernating animals suggest the effects of CR may be part of a spectrum of adaptive responses that include hibernation.CpsI 1 is specifically expressed in hepatocytes and epithelial cells of the intestinal mucosa. It is localized in mitochondria, where it catalyzes the condensation of metabolic ammonia and HCO 3Ϫ to carbamyl phosphate, the first step in the urea cycle in the liver (1, 2). CpsI is an abundant protein, comprising approximately 4% of liver protein (3, 4). CpsI levels are approximately 10 times lower in the small intestine (2).The enzyme is coded for by a single copy nuclear gene (5, 6). The gene is regulated cell-type specifically, developmentally, nutritionally, and hormonally. In the liver, the enzyme and its mRNA vary with the level of dietary protein (7, 8). In rats, cpsI precursor RNA and mRNA are induced 3-fold by isocaloric diets containing 20% versus 4% protein (9). Increased plasma glucagon concentrations (increased intracellular cAMP) have been shown to directly induce the level of cpsI mRNA (10 -13). Glucocorticoids also stimulate cpsI mRNA in the liver (13,14). This glucocorticoid response is reduced about 50% by insulin in hepatoma cells in culture (15). Epinephrine reduces the rate of CpsI synthesis in isolated rat hepatocytes (16). An attractive aspect of cpsI for studying the effects of nutrition on life-span is that enzyme activity and protein content do not vary with age in rodents, simplifying the analysis (17). Intestinal expression of the gene is not nutritionally or hormonally regulated, making possible cell type-specific studies of its regulation (11).The transcription factors and cis elements mediating the cell-specific, hormonal, and nutritional regulation of cpsI expression are not well characterized. Six sequence elements pro...

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“…Blood epinephrine levels do not change with CR in rats (50). Insulin may act by suppressing glucocorticoid stimulation of cpsI mRNA by 50% (15).…”

Section: Cpsi Levelsmentioning

confidence: 81%

Dietary Calorie Restriction in Mice Induces Carbamyl Phosphate Synthetase I Gene Transcription Tissue Specifically

Tillman

Dhahbi

Mote

et al. 1996

Journal of Biological Chemistry

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“…In addition, norepinephrine has been reported to show a chemotactic effect, thereby increasing bacterial migration to the intestinal mucosa in the host [31].Norepinephrine concentration in blood is higher in germ-free mice than in conventional rodents [32]. Though the level of 5-HT did not change significantly between ND-fed and HFD-fed mice, the level of 5-HT in the hippocampus of HFD-induced mice was increased by TP treatment with a significant difference.…”

Section: Discussionmentioning

confidence: 93%

Tremella polysaccharide mitigates high fat diet-induced anxiety-like behavior through the microbiota-gut-brain axis

Wu,

Chen,

Zhang

et al. 2024

Food Science and Human Wellness

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High-fat diet (HFD) consumption induces gut microbiota dysbiosis and neuropsychiatric disorders, including anxiety. Previous research found that Tremella polysaccharide (TP) exhibited neuroprotective effects in vitro and in vivo. This study aimed to investigate the beneficial effects of TP on HFD-induced anxiety-like behaviors and elucidate the underlying mechanisms from the point view of the microbiota-gut-brain axis. Two groups of HFD-induced obese mice were orally gavaged with low dose (TPL, 40 mg/kg) and high dose (TPH, 400 mg/kg) of TP. A 12-week administration of TPH could significantly improve anxiety-like behaviors in HFD mice. In the hippocampus, microglia activation, the expression of blood-brain barrier (BBB) markers, and the levels of two neurotransmitters (serotonin and norepinephrine) were countered by TPH in mice consuming HFD. Furthermore, TPH improved the intestinal permeability and immune response of the enterocytes in HFD-fed mice. The gut microbiota dysbiosis induced by HFD was also rebalanced by TP treatments, especially in Proteobacteria and its lower taxa. The correlational analysis also suggested that shifts of some microbial genera were closely associated with body weight and the parameters of behavioral tests. Interestingly, fecal microbiota transplantation (FMT) results indicated that fecal microbiota from TPH-treated obese mice could prevent HFD-induced anxiety-like behaviors, suppressing microglia activation and intestinal permeability. In conclusion, the present study indicated that TP intake is a promising dietary intervention strategy to prevent HFD-induced anxiety via the microbiota-gut-brain axis.

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“…In addition, recent studies have demonstrated that catecholamines also modulate host–microbial interface. Interestingly, in germ-free mice, serum norepinephrine is increased when compared with controls [ 45 ]. As described above, increased norepinephrine through the activity of tricyclic antidepressants is implicated in limiting glioma growth thus, our finding of decreased norepinephrine may help in driving glioma growth and progression.…”

Section: Discussionmentioning

confidence: 99%

“…These signaling molecules are able to interact with receptors of vagal afferents [52,53], as well as diffuse into circulation where they may act in an endocrine fashion [47,54]. Additionally, differences have been observed in serum norepinephrine levels between germ-free and controls in previous studies [45].…”

Section: Glioma Patients Controlsmentioning

confidence: 98%

Glioma induced alterations in fecal short-chain fatty acids and neurotransmitters

et al. 2020

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Aim: To explore fecal short-chain fatty acids and neurotransmitter alterations in a mouse–glioma model and glioma patients. Methods: Liquid chromatography–mass spectrometry and 16S rRNA-sequencing from fecal samples were performed to measure metabolite levels and taxa abundance in mice/humans. Mice underwent GL261 implantation with/without temozolomide. Glioma patients were compared with healthy controls. Results: Glioma altered several short-chain fatty acids and neurotransmitter levels. Reduced 5-hydroxyindoleaceic acid and norepinephrine levels were seen in mice and humans. Interestingly, temozolomide treatment abrogates the effects of glioma on fecal metabolites. Conclusion: Our findings demonstrate the interplay between glioma and the gut–brain axis. Further work is required to identify pathways within the gut–brain axis by which glioma influences and promotes the modulation of fecal metabolites and microbiome.

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The Influence of Dietary Restriction, Germ-Free Status, and Aging on Adrenal Catecholamines in Lobund-Wistar Rats

Cited by 8 publications

References 0 publications

Dietary Calorie Restriction in Mice Induces Carbamyl Phosphate Synthetase I Gene Transcription Tissue Specifically

Dietary Calorie Restriction in Mice Induces Carbamyl Phosphate Synthetase I Gene Transcription Tissue Specifically

Tremella polysaccharide mitigates high fat diet-induced anxiety-like behavior through the microbiota-gut-brain axis

Glioma induced alterations in fecal short-chain fatty acids and neurotransmitters

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