Project description:PGE2/EP3 signaling and m6A modification is required for brown adipocyte differentiation and BAT development, but the underlying mechanisms involved remain to be elucidated. The Arraystar mousen M6a-MRNA&lncRNA Epitranscriptomic microarray analysis was performed on mouse brown preadipocytes with or without EP3 deletion.
Project description:By conducting CUT&TAG, we reported that brown adipogenesis induction markedly increased ZFP410 occupancy on chromatin. GO analysis revealed that genes containing the ZFP410-bound peaks were enriched in fat cell differentiation. Consistently, binding signals of ZFP410 on the promoter regions of CHD4 as well as brown genes such as Pgc-1a, Prdm16 and Cyto C were markedly increased in differentiated pre-adipocytes compared to those in control cells.
Project description:Brown adipose tissue plays a crucial role in modulating whole-body energy expenditure through the thermogenic function of its mitochondrial respiratory chain. Pharmacological interventions targeting this function hold significant therapeutic promise. Thus, gaining a comprehensive understanding of the pathophysiological regulation of brown adipose tissue is imperative for future therapeutic applications. In this study, we investigated the metabolic mechanisms underlying the regulation of mature brown adipocyte function by the mitochondrial respiratory chain. Our findings indicate that deficiency in mitochondrial complex I in mature brown adipocytes leads to lipidomic remodeling. This remodeling results in an increase in arachidonic acid content and prostaglandin E2 (PGE2) production, leading to reduced transcriptional activity of peroxisome proliferator-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor alpha (PPARα) and alterations in the content of PPAR activator complexes, which consequently result in reduced brown adipocyte thermogenesis and peroxisomal gene expression in mature brown adipocyte. In summary, our study elucidates that the mitochondrial-derived arachidonic acid signal regulates brown adipocyte thermogenesis and peroxisome biogenesis by modulating the PPAR activator complex."
Project description:Sleep is essential for overall health, and its disruption is linked to increased risks of metabolic, cognitive, and cardiovascular dysfunctions; however, the mechanisms remain poorly understood. Using acute and chronic sleep deprivation (SD) mouse models, we found that dopaminergic (DA) neurons, particularly in theventral tegmental area (VTA), are activated during SD. Spatial micro-proteomics revealed distinctprotein expression profiles in VTA DA neurons: acute SD altered synaptic function, while chronic SDupregulated pathways linked to fatty acid oxidation, thermogenesis, and energy metabolism.Chronic SD increased basal metabolism (elevated oxygen consumption, respiratory entropy) andreduced brown adipose tissue (BAT) mass, accompanied by lipid droplet redistribution. Neuraltracing identified direct synaptic connections between VTA DA neurons and BAT. Targetedmanipulation of Eci1 in VTA DA neurons recapitulated SD-induced metabolic changes, includingreduced sleep, increased energy expenditure, and altered adipocyte morphology. These findingsestablish a brain-adipose axis through which VTA DA neurons requlate lipid metabolism andthermogenesis during sleep deprivation.
Project description:Gene expression profile from brown adipose tissues of Prdm16 knockout and wile type mice. Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development.
Project description:Various physiological stimuli, such as cold environment, diet, and hormones, trigger brown adipose tissue (BAT) to produce heat through sympathetic nervous system (SNS)- and -adrenergic receptors (ARs). The AR stimulation increases intracellular cAMP levels through heterotrimeric G proteins and adenylate cyclases, but the processes by which cAMP modulates brown adipocyte function are not fully understood. Here we described that specific ablation of cAMP production in brown adipocytes led to reduced lipolysis, mitochondrial biogenesis, uncoupling protein 1 (Ucp1) expression, and consequently defective adaptive thermogenesis. Elevated cAMP signaling by sympathetic activation inhibited Salt-inducible kinase 2 (Sik2) through protein kinase A (PKA)-mediated phosphorylation in brown adipose tissue. Inhibition of SIKs enhanced Ucp1 expression in differentiated brown adipocytes and Sik2 knockout mice exhibited enhanced adaptive thermogenesis at thermoneutrality in an Ucp1-dependent manner. Taken together, our data indicate that suppressing Sik2 by PKA-mediated phosphorylation is a requisite for SNS-induced Ucp1 expression and adaptive thermogenesis in BAT, and targeting Sik2 may present a novel therapeutic strategy to ramp up BAT thermogenic activity in humans.
Project description:Gene expression profile from brown adipose tissues of Prdm16 knockout and wile type mice. Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development. Brown adipose tissues were collected from Prdm16 knockout and wiletype mice with 4 biological replicates per condition. Experiment was done in two separate batch for 6-week-old and 11-month-old. Extracted RNA was hybridized to Agilent two-color arrays.
Project description:This project includes proteomic data of brown adipose tissue from mice modeled with Cuprizone 300mg/Kg/Day for one month versus wild-type mice. CB represents the brown adipose tissue from wild type mice. MB represents the brown adipose tissue from mice treated with cuprizone.