Effects of repeated Chlamydia pneumoniae inoculations on aortic lipid accumulation and inflammatory response in C57BL/6J mice.
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ABSTRACT:
SUBMITTER: Tormakangas L
PROVIDER: S-EPMC1230915 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesThyronamines are decarboxylated and deiodinated metabolites of thyroid hormones (THs). Of all possible thyronamine variants, only 3-iodothyronamine (3-T1AM) and iodine-free thyronamine (T0AM) have been detected in vivo. While intensive research has been done on the (patho-)physiological action of 3-T1AM, the role of T0AM has been studied less intensively.Study designWe determined whether a single pharmacological dose (50 mg/kg, i.p.) or repeated administration (5 mg/kg/day, i.p., for 7 days) of T0AM affects metabolism, cardiovascular function, or thermoregulation in male C57BL/6J mice. Since selenium (Se) is important for proper TH function and Se metabolism is affected by TH, we additionally analyzed Se concentrations in liver, serum, and kidney using total reflection X-ray analysis.ResultsA single injection of T0AM had no effect on heart rate, temperature, or activity as assessed by radio telemetry. Likewise, daily administration of T0AM did not alter body weight, food or water intake, heart rate, blood pressure, brown adipose tissue thermogenesis, or body temperature, and no significant differences in hepatic glycogen content or mRNA expression of genes involved in cardiovascular function or metabolic control were determined. Also, the X-ray analysis of Se concentrations revealed no significant changes. However, hepatic T0AM was significantly increased in the treated animals.ConclusionsIn summary, our data demonstrate that T0AM elicits no obvious metabolic, cardiovascular, or thermoregulatory activities in mice. As T0AM does also not interfere with TH or Se metabolism, we conclude that the deiodination of 3-T1AM to T0AM constitutes an efficient inactivation mechanism, terminating the actions of the more powerful precursor.
| S-EPMC5836237 | biostudies-literature
Project description:Ultrasonic vocalizations (USVs) are a major tool for assessing social communication in laboratory mice during their entire lifespan. At adulthood, male mice preferentially emit USVs toward a female conspecific, while females mostly produce ultrasonic calls when facing an adult intruder of the same sex. Recent studies have developed several sophisticated tools to analyze adult mouse USVs, especially in males, because of the increasing relevance of adult communication for behavioral phenotyping of mouse models of autism spectrum disorder (ASD). Little attention has been instead devoted to adult female USVs and impact of sex differences on the quantitative and qualitative characteristics of mouse USVs. Most of the studies have also focused on a single testing session, often without concomitant assessment of other social behaviors (e.g., sniffing), so little is still known about the link between USVs and other aspects of social interaction and their stability/variations across multiple encounters. Here, we evaluated the USVs emitted by adult male and female mice during 3 repeated encounters with an unfamiliar female, with equal or different pre-testing isolation periods between sexes. We demonstrated clear sex differences in several USVs' characteristics and other social behaviors, and these were mostly stable across the encounters and independent of pre-testing isolation. The estrous cycle of the tested females exerted quantitative effects on their vocal and non-vocal behaviors, although it did not affect the qualitative composition of ultrasonic calls. Our findings obtained in B6 mice, i.e., the strain most widely used for engineering of transgenic mouse lines, contribute to provide new guidelines for assessing ultrasonic communication in male and female adult mice.
| S-EPMC9330122 | biostudies-literature
Project description:Consumption of dietary protein at recommended levels is considered a potential strategy to promote satiety and weight management, but how protein from different dietary sources effect the obesity development, lipid metabolism, and gut microbiota is not known. This study focused on the effects of beef, casein, and soy protein diet on lipid metabolism, triglycerides accumulation, and microbial diversity in colon of C57BL/6J mice, which were given either low-fat diets (LFD, 12% Kcal) or high-fat diets (HFD, 60% Kcal) for 12 weeks. Body and liver weight increased significantly in mice fed a beef protein HFD (HFB), whereas reduced cumulative energy intake was seen in a soy protein HFD (HFS) group. HFB-fed mice showed signs of impaired glucose metabolism and insulin resistance along with a significant elevation in the concentration of triglycerides, LDL-cholesterol, total cholesterol, IL1β, TNF-α, IL-6, and leptin in serum. HFB also enhanced lipid accumulation in liver with increased activity of genes important for lipogenesis and hepatic cholesterol metabolism. A 16S rRNA gene sequencing indicated that HFD, regardless of proteins, significantly enhanced the ratio of Firmicutes to Bacteroidetes in colonic microbiota. However, HFB not only reduced the abundance of Akkermansia, compared with LFD independent of proteins, but also decreased the abundance of butyrate-producing bacteria such as Anaerotruncus, Butyricicoccus, and Lactobacillus (P < 0.05) compared with HFS and HFC. In conclusion, consumption of HFB does not only affect the gut microbiota composition but also increases the problems related to metabolic syndromes like dyslipidemia, hypercholesterolemia, and triglycerides accumulation in liver, which lead to systemic inflammation and its associated comorbidities, for example, impaired glucose metabolism and insulin resistance.
| S-EPMC6165900 | biostudies-literature
Project description:It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.
| S-EPMC8211526 | biostudies-literature
Project description:BackgroundThe mouse model of transverse aortic constriction (TAC) has been widely used as a cardiac stress in the investigation of the molecular mechanisms of cardiac hypertrophy. Recently, the International Knockout Mouse Consortium has selected the C57BL/6NTac (BL/6N) mouse strain to generate null alleles for all mouse genes; however, a range of genetic and cardiac phenotypic differences have been reported between this substrain and the commonly used C57BL/6J (BL/6J) substrain. It has been reported by Garcia-Menendez and colleagues that 12-week C57BL/6NTac mice are susceptible to heart failure but little is known about the cardiac remodeling in this substrain as cardiac function progresses from compensation to decompensation.MethodsBL/6J and BL/6N mice were subjected to pressure overload via TAC. The impact of both age and duration of cardiac pressure overload induced by TAC on cardiac remodelling were systematically assessed.ResultsOur data showed that BL/6N mice developed eccentric hypertrophy with age- and time-dependent deterioration in cardiac function, accompanied by considerable interstitial fibrosis. In contrast, BL/6J mice were more resilient to TAC-induced cardiac stress and developed variable cardiac phenotypes independent of age and the duration of pressure overload. This was likely due to the greater variability in pre-TAC aortic arch dimension as measured by echocardiography. In addition to increased expression of brain natriuretic peptide and collagen gene type 1 and 3, BL/6N mice also had greater angiotensin II type 2 receptor (AT2R) gene expression than BL/6J counterparts at baseline and after 2-weeks TAC, which may contribute to the exacerbated interstitial fibrosis.ConclusionsBL/6N and BL/6J mice have very different responses to TAC stimulation and these differences should be taken into consideration when using the substrains to investigate the mechanisms of hypertrophy and heart failure.
| S-EPMC7357793 | biostudies-literature
Project description:This study aimed to investigate the long-term effects of phytosterols (PS) intake on systemic and tissue-specific lipid metabolism in C57BL/6J mice. Healthy male C57BL/6J mice were randomly divided into control diet group (CS) and PS diet group (2% PS). After 28 weeks of continuous feeding, serums, livers, and lungs were collected for targeted free sterols quantification, biochemical tests, lipid profile detection, and RNA-seq analysis. Compared with the CS group, 2% PS supplementation significantly increased campesterol concentrations and its ratio to cholesterol in the serum, liver, and lung of mice, with cholestanol concentrations and its ratio to cholesterol decreased. Total cholesterol (TC) levels were reduced in the serum of the PS group (p < 0.05), with the triglyceride (TG) levels unchanged. In response to the decreased circulating cholesterol concentration, the expression of endogenous cholesterol synthesis genes was upregulated in the liver, but caused no obvious lipid accumulation and inflammatory cell infiltration. However, for peripheral tissues, long-term PS-fed mice exhibited diminished cholesterol synthesis, fatty acid transport, and oxidation in the lung. The results provided clear indication that 2% PS diet effectively reduced circulating TC levels in the healthy mice, with tissue-specific lipid metabolic regulation in the liver and the lung.
| S-EPMC9364813 | biostudies-literature
Project description:BackgroundObesity increases the risk for human abdominal aortic aneurysms (AAAs) and enhances Ang II (angiotensin II)-induced AAA formation in C57BL/6J mice. Obesity is also associated with increases in perivascular fat that expresses proinflammatory markers including SAA (serum amyloid A). We previously reported that deficiency of SAA significantly reduces Ang II-induced inflammation and AAA in hyperlipidemic apoE-deficient mice. In this study. we investigated whether adipose tissue-derived SAA plays a role in Ang II-induced AAA in obese C57BL/6J mice.MethodsThe development of AAA was compared between male C57BL/6J mice (wild type), C57BL/6J mice lacking SAA1.1, SAA2.1, and SAA3 (TKO); and TKO mice harboring a doxycycline-inducible, adipocyte-specific SAA1.1 transgene (TKO-Tgfat; SAA expressed only in fat). All mice were fed an obesogenic diet and doxycycline to induce SAA transgene expression and infused with Ang II to induce AAA.ResultsIn response to Ang II infusion, SAA expression was significantly increased in perivascular fat of obese C57BL/6J mice. Maximal luminal diameters of the abdominal aorta were determined by ultrasound before and after Ang II infusion, which indicated a significant increase in aortic luminal diameters in wild type and TKO-TGfat mice but not in TKO mice. Adipocyte-specific SAA expression was associated with MMP (matrix metalloproteinase) activity and macrophage infiltration in abdominal aortas of Ang II-infused obese mice.ConclusionsWe demonstrate for the first time that SAA deficiency protects obese C57BL/6J mice from Ang II-induced AAA. SAA expression only in adipocytes is sufficient to cause AAA in obese mice infused with Ang II.
| S-EPMC9050948 | biostudies-literature
Project description:The disruption of glucose homeostasis associated with the use of nicotine delivery systems may be due to a shift to lipid metabolism. Indirect calorimetry was used to measure the respiratory exchange ratio (RER) in female (N = 21) and male (N = 21) C57BL/6J mice exposed to room air (control) or e-cigarette vapor in a 1L chamber to test the hypothesis that lipid metabolism predominates in vaped mice. Metabolism was quantified via RER using a GA-200 gas analyzer (iWorx, Inc) and LabScribe v.4 (iWorx, Inc.) software. Blood glucose levels were assessed from a subset of the population using an Accu-Check glucometer (Roche Diagnostics, Inc.). Statistical analyses were conducted using R v.4.0.3. Median RER for controls was lower in females. Older females showed a reduction in RER when exposure occurred in the afternoon (p < 0.001), and in males when exposure occurred in the morning (p = 0.007). Glucose concentrations (mg/dL) were higher after e-cigarette inhalation compared with controls, but this difference was not significant (p = 0.464). The reduction in the respiratory exchange ratio supports the hypothesis that e-cigarette inhalation promotes lipid metabolism, and the magnitude of the effect is influenced by gender, age and time of day.
| S-EPMC8636804 | biostudies-literature
Project description:The effect of an atherogenic diet on inflammatory response and elicited peritoneal macrophage (Mphi) cholesterol accumulation in relation to aortic lesion formation was assessed in LDL receptor null (LDLr-/-) mice. Mice were fed an atherogenic or control diet for 32 weeks. The atherogenic relative to control diet resulted in significantly higher plasma monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) concentrations, more aortic wall Mphi deposition, higher serum non HDL-cholesterol concentrations and total cholesterol to HDL-cholesterol ratios, and greater accumulation of both aortic free and esterified cholesterol. Elicited peritoneal Mphi selectively accumulated longer chain unsaturated fatty acids in their membrane, independent of the dietary fatty acid profile. Elicited peritoneal Mphi isolated from mice fed the atherogenic relative to control diet had significantly less arachidonic acid levels, accumulated significantly higher esterified cholesterol, had significantly higher mRNA levels and secretion of MCP-1, and mRNA and protein levels of ATP-binding cassette A1. Diet treatment had no significant effect in elicited peritoneal Mphi on TNFalpha and IL-6 mRNA levels and secretion. These data suggest that the atherogenic relative to control diet resulted in higher plasma inflammatory factor concentrations, less favorable lipoprotein profile, higher elicited peritoneal Mphi cholesterol accumulation and inflammatory factor secretion, and more aortic wall Mphi deposition, which in turn were associated with greater aortic cholesterol accumulation.
| S-EPMC2935317 | biostudies-literature
Project description:The classic piebald mutation in the endothelin receptor type B (Ednrb) gene was found on rolling Nagoya genetic background (PROD-s/s) mice with white coat spotting. To examine whether genetic background influenced the phenotype in the piebald mutant mice, we generated a congenic strain (B6.PROD-s/s), produced by repeated backcrosses to the C57BL/6J (B6) strain. Although B6.PROD-s/s mice showed white coat spotting, 7% of B6.PROD-s/s mice died between 2 and 5 weeks after birth due to megacolon. The PROD-s/s, s/s and Japanese fancy mouse 1 (JF1) strains, which also have piebald mutations on different genetic backgrounds with B6, showed only pigmentation defects without megacolon. In expression analyses, rectums of B6.PROD-s/s with megacolon mice showed ~5% of the level of Ednrb gene expression versus B6 mice. In histological analyses, aganglionosis was detected in the rectum of megacolon animals. The aganglionic rectum was thought to lead to severe constipation and intestinal blockage, resulting in megacolon. We also observed an abnormal intestinal flora, including a marked increase in Bacteroidaceae and Erysipelotrichaceae and a marked decrease in Lactobacillus and Clostridiales, likely inducing endotoxin production and a failure of the mucosal barrier system, leading ultimately to death. These results indicate that the genetic background plays a key role in the development of enteric ganglion neurons, controlled by the Ednrb gene, and that B6 has modifier gene (s) regarding aganglionosis.
| S-EPMC4363017 | biostudies-literature