LPS induces rapid increase in GDF15 levels in mice, rats and humans but is not required for anorexia in mice

Growth differentiation factor 15 (GDF15), a TGFβ superfamily cytokine, acts through its receptor, GDNF-family receptor α-like (GFRAL), to suppress food intake and promote nausea. GDF15 is broadly expressed at low levels but increases in states of disease such as cancer, cachexia, and sepsis. Whether GDF15 is necessary for inducing sepsis associated anorexia and body weight loss is currently unclear. To test this we used a model of moderate systemic infection in GDF15KO and GFRALKO mice with lipopolysaccharide (LPS) treatment to define the role of GDF15 signaling in infection-mediated physiologic responses. Since physiologic responses to LPS depend on housing temperature, we tested the effects of subthermoneutral and thermoneutral conditions on eliciting anorexia and inducing GDF15. Our data demonstrate a conserved LPS-mediated increase in circulating GDF15 levels in mouse, rat and human. However, we did not detect differences in LPS induced anorexia between WT and GDF15KO or GFRALKO mice. Further, there were no differences in anorexia or circulating GDF15 levels at either thermoneutral or subthermoneutral housing conditions in LPS treated mice. These data demonstrate that GDF15 is not necessary to drive food intake suppression in response to moderate doses of LPS.

THI and health estimates of Jersey crossbred calves reared in different housing system in the lower Gangetic plains of West Bengal

Housing and socialization have always played a pivotal role on overall health and welfare of the young calves. Therefore, the study was undertaken to compare the performance of the calves when kept indoors in enclosures (Treatment, T) versus semi covered houses with provision of open space (Control, C), respectively. Calves in semi covered houses (C) was found to display profound results on faecal score (P<0.01) and body weight (P<0.05). Besides, the housing temperature in the treatment sheds was significantly higher (P<0.01) during the mornings in monsoon season although humidity was reportedly higher at all seasons; monsoon (P<0.01), post monsoon (P<0.05) and winters (P<0.01), respectively. The greatest THI were recorded in the month of July (76.72) in Control group (C) and August (79.67) in Treatment group. Besides with the highest THI (74.50±0.81, P<0.01) with elevated rectal temperatures (101.22±0.15 °F, P<0.05) was recorded in the treatment (T) calves. However, a positive significant correlation of rectal temperature with THI (r=0.434; P<0.01) and respiratory rate (r=0.339; P<0.01) wasobserved in the experimental calves. The calves in C group had fewer incidences of respiratory illness and problems of diarrhoea when compared to the T calves. Therefore, maintaining fewer calves in semi covered houses with provision of open space was found to be beneficial on health, growth and housing environment of the calves.

The confounding effects of sub-thermoneutral housing temperatures on aerobic exercise-induced adaptations in mouse subcutaneous white adipose tissue

Mice are the most commonly used model organism for human biology, and failure to acknowledge fundamental differences in thermal biology between these species has confounded the study of adipose tissue metabolism in mice and its translational relevance to humans. Here, using exercise biochemistry as an example, we highlight the subtle yet detrimental effects sub-thermoneutral housing temperatures can have on the study of adipose tissue metabolism in mice. We encourage academics and publishers to consider ambient housing temperature as a key determinant in the methodological conception and reporting of all research on rodent white adipose tissue metabolism.

The Effect of Environmental Factor, Population and Age of Duck on Egg Production

Duck is one of the commodities that contribute to the national livestock production and Central Java is home to the fourth biggest duck population after West Java, South Sulawesi and East Java. The 2019 egg production in Central Java was 36.174 tons or 11.3% of the total egg production nationwide. Accordingly, it is important to investigate the effect of environmental factor, total number and age of ducks on egg production in Central Java. Specifically, this study aimed to observe the effect of region on egg production and feed conversion ratio (FCR) and the total livestock (chicken), age (month), stocking density (ducks/m2), internal housing temperature (oC), and humidity (%) on Hen day production/HDP. A survey engaging purposive random sampling was conducted on the population of duck farming in Central Java especially Tegal, Pemalang and Brebes districts. The data were subjected to General Linear Model (GLM) and a regression-correlation analysis using an SPSS program. The result showed that region significantly affected hen day production (HDP) but did not affect FCR. Housing temperature affected HDP by 14.9% and the higher the temperature, the lower the HDP. Duck age affected HDP by 11.7%, and the older the ducks the lower the egg production. Duck population, stocking density and humidity did not significantly affect egg production. Conclusively, duck egg production (HDP) is significantly affected by temperature inside the housing and the duck age.

Thermoneutrality and Immunity: How Does Cold Stress Affect Disease?

One of the major challenges the scientific community faces today is the lack of translational data generated from mouse trials for human health application. Housing temperature-dependent chronic cold stress in laboratory rodents is one of the key factors contributing to lack of translatability because it reveals major metabolic differences between humans and rodents. While humans tend to operate at temperatures within their thermoneutral zone, most laboratory rodents are housed at temperatures below this zone and have an increased energy demand to generate heat. This has an impact on the immune system of mice and thus affects results obtained using murine models of human diseases. A limited number of studies and reviews have shown that results obtained on mice housed at thermoneutrality were different from those obtained from mice housed in traditional housing conditions. Most of those studies, focused on obesity and cancer, found that housing mice at thermoneutrality changed the outcomes of the diseases negatively and positively, respectively. In this review, we describe how thermoneutrality impacts the immune system of rodents generally and in the context of different disease models. We show that thermoneutrality exacerbates cardiovascular and auto-immune diseases; alleviates asthma and Alzheimer’s disease; and, changes gut microbiome populations. We also show that thermoneutrality can have exacerbating or alleviating effects on the outcome of infectious diseases. Thus, we join the call of others in this field to urge researchers to refine murine models of disease and increase their translational capacity by considering housing at thermoneutrality for trials involving rodents.

Barriers in translating preclinical rodent exercise metabolism findings to human health

Physical inactivity and low aerobic capacity are primary drivers of chronic disease pathophysiology and are independently associated with all-cause mortality. Conversely, increased physical activity and exercise are central to metabolic disease prevention and longevity. Although these relationships are well characterized in the literature, what remains incompletely understood are the mechanisms by which physical activity/exercise prevents disease. Given methodological constraints of clinical research, investigators must often rely on preclinical rodent models to investigate these potential underlying mechanisms. However, there are several key barriers to translating exercise metabolism findings from rodent models to application in human health. These barriers include housing temperature, nutrient metabolism, exercise modality, exercise testing, and sex differences. Increased awareness and understanding of these barriers will enhance the ability to impact human health through more appropriate experimental design and interpretation of data within the context of these factors.

Housing temperature affects the circadian rhythm of hepatic metabolism and clock genes

Environmental temperature remarkably impacts on metabolic homeostasis, raising a serious concern about the optimum housing temperature for translational studies. Recent studies suggested that mice should be housed slightly below their thermoneutral temperature (26°C). On the other hand, the external temperature, also known as a zeitgeber, can reset the circadian rhythm. However, whether housing temperature affects the circadian oscillators of the liver remains unknown. Therefore, we have compared the effect of two housing temperatures, namely 21°C (conventional; TC) and 26°C (thermoneutral; TN), on the circadian rhythms in mice. We found that the rhythmicity of food intake showed an advanced phase at TC, while the activity was more robust at TN, with a prolonged period onset. The serum levels of norepinephrine were remarkably induced at TC, but failed to oscillate rhythmically at both temperatures. Likewise, circulating glucose levels were increased but were non-rhythmic under TC. Both total cholesterol and triglycerides levels were induced at TN, but showed an advanced phase under TC. Additionally, the expression of hepatic metabolic genes and clock genes remained rhythmic at both temperatures, with the exception of G6Pase, Fasn, Cpt1a and Cry2, at TN. Nevertheless, the liver histology examination did not show any significant changes in response to housing temperature. Although the non-consistent trends of phase changes in each temperature, our results suggest a non-reductant role of temperature in mouse internal rhythmicity resetting. Thus, the temperature-controlled internal circadian synchronization within organs should be taken into consideration when optimizing housing temperature for mice.