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Eisner, K.

Publications and source records attributed to Eisner, K..

3 recordsLinked to original sources

Tirzepatide and Intermittent Cold Exposure Independently Improve Glucose Homeostasis in DIO Mice Housed at Thermoneutrality

Obesity is considered a risk factor for metabolic diseases, including type 2 diabetes, and results from an imbalance between energy intake and energy expenditure. While pharmacological approaches such as tirzepatide, a dual GIP/GLP-1 receptor agonist, effectively reduce food intake and body weight, strategies that enhance energy expenditure (EE) may provide complementary metabolic benefits. Intermittent cold exposure (ICE) is one such approach that enhances EE and improves glucose homeostasis independent of weight loss. However, the combined effects of these interventions remain unexplored. In this study, we investigated the individual and combined effects of tirzepatide and ICE on body composition, energy metabolism, and glucose homeostasis in diet-induced obese (DIO) male and female mice housed at thermoneutrality. After 8 weeks of 45% high-fat diet feeding, mice received tirzepatide (10 nmol/kg) or vehicle and were exposed to ICE (4{degrees}C, 1 h/day, 5 days/week) or remained at thermoneutrality for 3 weeks. Energy expenditure and substrate utilization were assessed using indirect calorimetry at thermoneutrality and during an acute 1 h cold challenge. Tirzepatide reduced body weight, food intake, and adiposity in both sexes, with a greater reduction in lean mass in males. ICE did not affect body weight but improved glucose homeostasis. At thermoneutrality, tirzepatide did not alter total EE but lowered respiratory exchange ratio (RER), indicating a shift toward lipid utilization. In contrast, ICE increased energy expenditure and fat oxidation, with no additive effects observed when combined with tirzepatide. Together, these findings highlight that targeting both energy intake and expenditure represents complementary, but not necessarily additive approaches to improving metabolic health.

physiology↗

Topical application of the cold-mimetic L-menthol decreases wheel running without affecting the beneficial effects of voluntary exercise in mice

Topical application of L-menthol, a pharmacological cold-mimetic and agonist of the cold-sensing receptor TRPM8 (Transient Receptor Potential Cation Channel Subfamily M Member 8), has been shown to stimulate brown adipose tissue (BAT) thermogenesis and reduce weight gain in both obese and lean male mice, without affecting energy intake. While these findings suggest that L-menthol could offer a novel approach to prevent weight gain, its potential to enhance the benefits of exercise on whole-body metabolic health remains unexplored. In this study, we investigated whether daily topical L-menthol application, combined with voluntary wheel running, could enhance exercise-induced improvements in metabolic health in male and female C57BL/6J mice housed at thermoneutrality (29{degrees}C). Our results demonstrated that although L-menthol treatment reduced voluntary wheel running distance there was still a main effect of exercise to reduce fat mass, weight gain and improve glucose tolerance. Indirect calorimetry revealed that L-menthol increased total energy expenditure, potentially explaining improvements in metabolic health despite reductions in voluntary wheel running. These findings suggest that although L-menthol does not enhance the effects of voluntary exercise, it remains a promising strategy for improving metabolic health. Key pointsO_LIL-menthol treatments led to a reduction in voluntary wheel running distance C_LIO_LIDespite the reduced voluntary exercise with L-menthol, wheel running led to significant reductions in fat mass as well as improved glucose tolerance C_LIO_LITreatment with L-menthol increased energy expenditure perhaps providing an explanation for exercise-induced improvements in indices of metabolic health despite reduction in wheel running C_LI

physiology↗

Physiological stress drives the emergence of a Salmonella subpopulation through ribosomal RNA regulation

Bacteria undergo cycles of growth and starvation, to which they must adapt swiftly. One important strategy for adjusting growth rates relies on ribosomal levels. While high ribosomal levels are required for fast growth, their dynamics during starvation remain unclear. Here, we analyzed ribosomal RNA (rRNA) content of individual Salmonella cells using Fluorescence In-Situ Hybridization (rRNA-FISH). During the transition from exponential to stationary phase we measured a dramatic decrease in rRNA numbers only in a subpopulation, resulting in a bimodal distribution of cells with high and low rRNA content. We showed that the two subpopulations are phenotypically distinct when subjected to nutritional upshifts. Using a transposon screen coupled with rRNA-FISH, we identified two mutants acting on rRNA transcription shutdown and degradation, that abolished the formation of the subpopulation with low rRNA content. Our work suggests that Salmonella employs a bet-hedging strategy in regulating ribosomal levels that may be beneficial for survival.

microbiology↗