The aging mouse microbiome has obesogenic characteristics.

BACKGROUND: During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice. METHODS: Fecal and blood samples from adult (n = 42, 100-300 days) and aging (n = 32, 550-750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin. RESULTS: We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces. CONCLUSIONS: We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.

Impacts of previous heatstroke history on physiological parameters eHSP72 and biomarkers of oxidative stress in military working dogs.

Heatstroke (HS) is an acute, progressive life-threatening emergency. Animals, including military working dogs (IDFMWD), rapidly activate cytoprotective processes, e.g., heat shock proteins (HSPs) and antioxidative molecules, in response to heat stress. We hypothesized that serum HSPs (eHSP72) and oxidative stress markers would differ in IDFMWD with a history of HS compared with controls and thus could be used to detect susceptibility to recurrent HS. eHSPs concentration, oxidative stress markers, and systemic physiological parameters were studied in dogs with and without histories of HS, undergoing indoor or outdoor training. Treadmill physical performance tests (PPTs) were conducted indoors at 22 °C (groups C-I and HS-I) or outdoors under heat stress conditions of 36 °C; 60% humidity (groups C-O and HS-O). Pre-, immediately post-, and 45 min post-PPT heart rate (HR), respiratory rate, and rectal temperature (Tre) were recorded in all dogs. Likewise, blood samples were collected and eHSP72, venous blood gas analysis, and lactate and creatine kinase activity (CK) were assayed. Serum uric acid (sUA) and total serum redox potential (TRP) were measured only in the indoor group. Immediately post-PPT under both environmental conditions, Tre, HR, eHSP, sUA, and TRP (only measured in indoor PPT) significantly (P < 0.05) increased, whereas venous blood pH and bicarbonate decreased significantly (P < 0.05). Between groups comparisons demonstrated significant differences in basal HR and post-PPT Tre immediately after outdoor PPT. eHSP72 induction, CK, sUA, and serum TRP remained significantly higher in the HS group during post-PPT recovery. Taken together, animals with a history of HS have different results, and this signature of previous HS may predict altered heat sensitivity.

Long-lived weight-reduced αMUPA mice show higher and longer maternal-dependent postnatal leptin surge.

We investigated whether long-lived weight-reduced αMUPA mice differ from their wild types in postnatal body composition and leptin level, and whether these differences are affected by maternal-borne factors. Newborn αMUPA and wild type mice had similar body weight and composition up to the third postnatal week, after which αMUPA mice maintained lower body weight due to lower fat-free mass. Both strains showed a surge in leptin levels at the second postnatal week, initiating earlier in αMUPA mice, rising higher and lasting longer than in the wild types, mainly in females. Leptin level in dams' serum and breast milk, and in their pup's stomach content were also higher in αMUPA than in the WT during the surge peak. Leptin surge preceded the strain divergence in body weight, and was associated with an age-dependent decrease in the leptin:fat mass ratio-suggesting that postnatal sex and strain differences in leptin ontogeny are strongly influenced by processes independent of fat mass, such as production and secretion, and possibly outside fat tissues. Dam removal elevated corticosterone level in female pups from both strains similarly, yet mitigated the leptin surge only in αMUPA-eliminating the strain differences in leptin levels. Overall, our results indicate that αMUPA's postnatal leptin surge is more pronounced than in the wild type, more sensitive to maternal deprivation, less related to pup's total adiposity, and is associated with a lower post-weaning fat-free mass. These strain-related postnatal differences may be related to αMUPA's higher milk-borne leptin levels. Thus, our results support the use of αMUPA mice in future studies aimed to explore the relationship between maternal (i.e. milk-borne) factors, postnatal leptin levels, and post-weaning body composition and energy homeostasis.

Heat acclimation memory: do the kinetics of the deacclimated transcriptome predispose to rapid reacclimation and cytoprotection?

Faster reinduction of heat acclimation (AC) after its decline indicates "AC memory." Our previous results revealed involvement of epigenetic mechanisms of transcriptional regulation. We hypothesized that the decline of AC (DeAC) is a period of "dormant memory" during which many processes are alerted to enable rapid reacclimation (ReAC). Using a genomewide approach we studied the AC, DeAC, and ReAC transcriptomes, to uncover hallmark pathways linked to "molecular memory" in the cardioacclimatome. Fifty rats subjected to heat acclimation [34°C for 2d (AC2d) or 30d (AC30)], DeAC (24°C, 30 days), ReAC (34°C, 2 days), and untreated controls were used. The GeneChip Rat Gene 1.0 ST Array was employed for left ventricular (cardiac) mRNA hybridization. Three independent bioinformatic analyses showed that 1) during AC2d enrichment of DNA impair/repair-linked genes is seen, and this is the molecular on-switch of acclimation; 2) genes activated in AC30 underlie the qualitative physiological adaptations of cardiac performance; 3) particular molecular programs encompassing constitutive upregulation of p38 MAPK, Jak/Stat, and Akt pathways and targets are specifically activated during DeAC and ReAC; and 4) epigenetic markers such as linker histones (histones H1 cluster), associated with nucleosome spacing, transcriptional chromatin modifiers, poly-(ADP-ribose) polymerase-1 (PARP1) linked to chromatin compaction, and microRNAs are only altered during DeAC/ReAC. The latter are newcomers to the AC/DeAC puzzle. We suggest that these transcriptional responses maintain euchromatin and proteostasis and enable faster physiological recovery upon ReAC by rapidly reestablishing the protected acclimated cardiophenotype. We propose that the cardiac AC model can be applied to acclimation processes in general.

Two years of combined high-intensity physical training and heat acclimatization affect lymphocyte and serum HSP70 in purebred military working dogs.

Military working dogs in hot countries undergo exercise training at high ambient temperatures for at least 9 mo annually. Physiological adaptations to these harsh conditions have been extensively studied; however, studies focusing on the underlying molecular adaptations are limited. In the current study, military working dogs were chosen as a model to examine the effects of superimposing endurance exercise on seasonal acclimatization to environmental heat stress. The lymphocyte HSP70 profile and extracellular HSP70 were studied in tandem with physiological performance in the dogs from their recruitment for the following 2 yr. Aerobic power and heat shock proteins were measured at the end of each summer, with physical performance tests (PPTs) in an acclimatized room (22°C). The study shows that together with a profound enhancement of aerobic power and physical performance, hsp72 mRNA induction immediately post-PPT and 45 min later, progressively increased throughout the study period (relative change in median lymphocyte hsp72 mRNA first PPT, 4.22 and 12.82; second PPT, 17.19 and 109.05, respectively), whereas induction of HSP72 protein was stable. These responses suggest that cellular/molecular adaptive tools for maintaining HSP72 homeostasis exist. There was also a significant rise in basal and peak median optical density extracellular HSP at the end of each exercise test (first PPT, 0.13 and 0.15; second PPT, 1.04 and 1.52, respectively). The relationship between these enhancements and improved aerobic power capacity is not yet fully understood.