Project description:Brown adipose tissue (BAT) is specialized for dissipating energy in the form of heat. BAT-mediated heat production is critical for effective adaption of newborns to the extrauterine environment. However, very little is known about whether and how fetal BAT development is modulated in-utero in response to changes in maternal thermal environment during pregnancy. The present study aims at determining whether maternal cold exposure influences fetal BAT development via placental remodeling. BL6 female mice were acclimated at 28C or 18C for 7 days prior to mating with male mice and maintained at their respective temperature until embryonic day 18.5. Placental and fetal BAT samples were collected for transcriptome analysis.
Project description:Research in recent years has focused on environmental effects that control tissue functionality and systemic metabolism. We show here in a retrospective analysis that presence of brown adipocytes and date of birth are correlated and linked to BMI. In a mouse model system, we demonstrate that pre-conception cold exposure leads to improved systemic metabolism and protects from diet induced obesity, through the sperm via the paternal lineage. Using a brown fat ablation model, we show that this effect is mediated by brown adipose tissue. Furthermore, through RNAseq and DNA methylation analysis we identify Adrb3 as a putative signaling mechanism which could mediate the effects of pre-conception cold exposure and could account for the heterogeneity of brown adipose tissue responsiveness. Taken together, our results identify paternal cold exposure as a stimulus which induces a hyper-active state in brown adipose tissue leading to improved adaptation to overnutrition and hypothermia in the offspring.
Project description:We report the impact of maternal fish oil intake during gestation and lactation on the fetal brown fat development and metabolic health in later life
Project description:Cold exposure imposes a metabolic challenge to mammals that must be met by a coordinated repsonse in different tissues to prevent hypothermia. This study reports analysis of transcriptome profiles in brown adipose tissue, liver, white adipose of mice in repsonse to 24 hour cold exposure Total RNA was extracted from brown adipose, whie adipose and liver from cold treated and control plants. 3 replicates of brown adipose and white adipose and 2 replicates of liver samples.
Project description:To investigate the Cold exposure adaptation under macrophage-specific Mafb deficiency, we put the Mafbf/f (Control) mice and Mafbf/f::LysM-cre (Macrophage specific Mafb deficient) under cold exposure for 10 days and collected the interscapular brown adipose tissue (iBAT) of these mice to compare the changes using RNA sequencing.
Project description:We applied a deep-sequencing based method – digital gene expression profiling (DGEP), to investigate gene expression in interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) in acute cold exposure
Project description:Brown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure (EE) and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show by phosphoproteomics that cAMP activates distinct signaling pathways in brown progenitors, with the cAMP-EPAC1 axis enhancing proliferation and differentiation of thermogenic but not white adipocytes. Further analysis revealed that a specific subpopulation of preadipocytes that are PDGFRα-positive express EPAC1. In vivo, pharmacological activation of EPAC1 enhances BAT growth and browning of white fat, leading to increased EE and reduced diet-induced adiposity. In contrast, mice lacking EPAC1 in PDGFRα-positive preadipocytes show the opposite phenotype. Importantly, EPAC1 activation enhances proliferation and differentiation of human brown adipocytes and human brown fat organoids. Interestingly, a coding variant in EPAC1 that positively correlates with BMI abolishes norepinephrine-induced proliferation of brown adipocytes. Thus, EPAC1 might be an attractive target to enhance thermogenic adipocyte number and EE to combat metabolic diseases.
Project description:Cold exposure imposes a metabolic challenge to mammals that must be met by a coordinated repsonse in different tissues to prevent hypothermia. This study reports analysis of transcriptome profiles in brown adipose tissue, liver, white adipose of mice in repsonse to 24 hour cold exposure
Project description:We applied a deep-sequencing based method – digital gene expression profiling (DGEP), to investigate gene expression in interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) in acute cold exposure Examination of gene expression level in 3 different adipose tissues in 3 time points, day0, day2 and day4 in cold exposure.