Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes
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PROVIDER: PRJNA1235202 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes.
| PRJNA942971 | ENA
Project description:mRNA expression profiles from interscapular brown adipose (iBAT) tissue male ATF4 BAT KO mice and their WT counterparts after 3 days of cold exposure.
2024-01-24 | GSE227060 | GEO
Project description:mRNA expression profiles from interscapular brown adipose (iBAT) tissue male ATF4 BAT KO mice and their WT counterparts after 12 weeks of high fat diet.
2025-07-28 | GSE291759 | GEO
Project description:Brown adipose tissue (BAT) generates heat via uncoupled respiration, providing mammals with an evolutionary defense against environmental cold. Although the molecular pathways by which cold activates brown adipocytes are well understood, little is known about how BAT maintains its thermogenic capacity during adaptation to environmental warmth. Here, we identify the transcriptional repressor BCL6 as the switch for maintaining brown adipocyte cellular identity under warm conditions. Mice lacking BCL6 in their brown adipocytes display normal thermogenic responses when housed in a cool environment, but fail to maintain thermogenic fitness when housed under warm conditions. In a temperature-dependent manner, BCL6 suppresses apoptosis, fatty acid storage, and coupled respiration to maintain thermogenic competence in brown adipocytes. Enhancer analysis revealed that BCL6 reinforces brown-specific while opposing white-specific enhancers to maintain cellular identity. Thus, unlike other regulators, BCL6 is dispensable for differentiation and activation of brown adipocytes, but specifically required for their maintenance in warmth.
2019-08-29 | GSE122746 | GEO
Project description:Obesity and diabetes result from disrupted energy homeostasis, highlighting the importance of identifying molecular mechanisms that enhance energy expenditure. Brown adipose tissue (BAT) dissipates energy through mitochondria-dependent non-shivering thermogenesis, yet the transcriptional regulators coordinating this process remain incompletely defined. In this study, we identify activating transcription factor 5 (ATF5) as a key regulator of thermogenic gene expression and mitochondrial metabolism in brown adipocytes. Cold exposure and β3-adrenergic stimulation robustly induced Atf5 expression in BAT and differentiated brown adipocytes, coinciding with activation of canonical thermogenic programs. Mechanistically, ATF5 functions downstream of a nuclear PKA–ERK signaling axis, where nuclear ERK1/2 activation is required for ATF5 induction and subsequent upregulation of UCP1. Loss of Atf5 impaired thermogenic transcription, suppressed mitochondrial unfolded protein response (UPRmt) and lipolytic gene expression, and reduced mitochondrial oxidative capacity and metabolic flexibility. Transcriptomic profiling revealed broad downregulation of fatty acid oxidation, β-oxidation, oxidative phosphorylation, and thermogenic pathways in Atf5-deficient brown adipocytes. Collectively, these data establish ATF5 as a central transcriptional regulator that integrates mitochondrial metabolism, lipid catabolism, and thermogenic activation in brown adipocytes, providing mechanistic insight into energy expenditure regulation.
2026-05-31 | GSE315093 | GEO
Project description:Mitochondrial respiration is essential for Ucp1-mediated thermogenesis in brown adipocytes, where heat is produced through oxygen-dependent mitochondrial activity. To investigate the role of complex IV in this process, we generated brown adipocyte–specific Cox10 knockout mice (Cox10BKO), as COX10 is required for the assembly of cytochrome c oxidase (complex IV). Cox10-deficient brown adipocytes displayed markedly reduced complex IV activity and were unable to support Ucp1-dependent thermogenesis. Previous studies have shown that disruption of mtDNA-encoded electron transport chain (ETC) gene expression abolishes the Ucp1-mediated thermogenesis but induces an alternative, ATF4-driven thermogenic program involving increased protein turnover. In Cox10-deficient brown adipocytes, ATF4 target genes were strongly induced; however, this alternative thermogenic pathway did not occur because global protein synthesis was suppressed, likely reflecting severe mitochondrial stress. Interestingly, the Cox10BKO mice were protected against high-fat-diet-induced metabolic abnormalities. These findings reveal that brown adipocytes can influence whole-body metabolic homeostasis independently of their canonical thermogenic function, suggesting previously unrecognized endocrine or metabolic roles for brown fat.
2026-05-27 | GSE316308 | GEO
Project description:Sustained responses to transient stimuli are important for animals to survive and reproduce in their environment. However, the mechanisms that underlie altered responses to temporary shifts in abiotic factors, such as temperature, remain poorly understood. Here, we find that transient cold exposure leads to sustained transcriptional and metabolic adaptations in brown adipose tissue, which are critical for an improved thermogenic response to secondary cold encounter. Primary thermogenic challenge triggers the delayed induction of a lipid biosynthesis program even after cessation of the original stimulus, which protects from subsequent exposures. By combining single-nucleus RNA sequencing, spatial transcriptomics, and immunofluorescence imaging, we discover that this lipogenic response is carried out by a distinct subpopulation of brown adipocytes that is localized along the perimeter of classical Ucp1high brown adipocytes. The protective effect of the lipogenic program is associated with the production of acyl carnitines, and supplementation of acyl carnitines recapitulates improved secondary cold responses even in the absence of lipogenesis. Overall, our data highlight the importance of heterogenous brown adipocyte populations for “thermogenic memory” in the setting of repeated cold exposure, which may have implications for therapeutic efforts leveraging short-term thermogenesis to counteract the hypercaloric state of obesity.
2023-09-11 | GSE218709 | GEO
Project description:The activity of brown fat, a tissue mediating non-shivering thermogenesis, is associated with protection against obesity, diabetes, and cardiovascular disease. In response to thermogenic stimuli, brown adipose tissue (BAT) increases its activity through extensive cellular and tissue plasticity. While macroautophagy is typically inhibited during BAT thermogenic activation, we found that chaperone-mediated autophagy (CMA), a selective type of autophagy, is instead induced. CMA induction enhances both basal and cAMP-stimulated activity of brown adipocytes, as evidenced by increased expression of thermogenesis-related genes, enhanced release of brown adipokines, elevated cellular oxidative activity, and increased lipolysis. In aging, when BAT activity declines, LAMP2A—the limiting CMA component—is downregulated in BAT. However, pharmacological activation of CMA restores BAT activity in aged mice. To investigate the consequences of this CMA failure in BAT, we generated brown adipocytes knock down for LAMP2A and using comparative proteomics identified that CMA regulates levels of proteins involved in BAT thermogenic and metabolic activity. We demonstrate that selective CMA blockade in interscapular BAT in mice leads to reduced energy expenditure, increased triglyceridemia, lower expression of thermogenic markers and BAT-secretory functions, and to accumulation of thermogenesis repressors upon thermogenic activation. Overall, these findings support the essential role of CMA in BAT function and adaptation to thermogenic activation. CMA facilitates the timely degradation of thermogenic repressors, thereby promoting adaptive enhancement of thermogenic activity.
2025-09-30 | PXD062807 | Pride
Project description:Multi-omics analysis of thermogenic lipolysis in brown adipocytes
| PRJNA1234155 | ENA
Project description:A subpopulation of lipogenic brown adipocytes drives thermogenic memory
| PRJNA905100 | ENA