Multi-omics analysis of thermogenic lipolysis in brown adipocytes
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ABSTRACT:
PROVIDER: PRJNA1234155 | ENA |
REPOSITORIES: ENA
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Project description:The integration of omics technologies into molecular biological research has transformed it into a field where a system can be investigated as a whole by combining information from multiple biochemical layers. This extension of traditional molecular biology, where various data sources are considered independently, offers novel insights into complex molecular interactions. Here, we present a multi-omics analysis of murine brown adipocytes undergoing thermogenic lipolysis, which is part of the non-shivering response to cold. Through combining information from multiple types of biomolecules, we describe what is important for each biochemical layer, and the system as a whole, at different time points. Furthermore, a classification of data integration approaches for multi-omics data analysis is presented.
2025-09-22 | PXD061570 | Pride
Project description:The integration of omics technologies into molecular biological research has transformed it into a field where a system can be investigated as a whole by combining information from multiple biochemical layers. This extension of traditional molecular biology, where various data sources are considered independently, offers novel insights into complex molecular interactions. Here, we present a multi-omics analysis of murine brown adipocytes undergoing thermogenic lipolysis, which is part of the non-shivering response to cold. Through combining information from multiple types of biomolecules, we describe what is important for each biochemical layer, and the coordinated molecular responses across different layers at the system level, at different time points. Furthermore, a classification of data integration approaches for multi-omics data analysis is presented, and their applications in our study are compared, providing insights into the focus and effectiveness of these methods.
2025-07-30 | GSE291567 | GEO
Project description:β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. Here we have used pharmacological inhibitors and a novel direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in brown adipocytes. We show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on brown adipocyte transcription and function.
2022-05-15 | GSE202833 | GEO
Project description:β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. Here we have used pharmacological inhibitors and a novel direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in brown adipocytes. We show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on brown adipocyte transcription and function.
2022-05-21 | GSE203247 | GEO
Project description:β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. Here we have used pharmacological inhibitors and a novel direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in brown adipocytes. We show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on brown adipocyte transcription and function.
2022-05-15 | GSE202834 | GEO
Project description:β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. Here we have used pharmacological inhibitors and a novel direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in brown adipocytes. We show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on brown adipocyte transcription and function.
2022-06-03 | GSE205127 | GEO
Project description:β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. Here we have used pharmacological inhibitors and a novel direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in brown adipocytes. We show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on brown adipocyte transcription and function.
2022-06-03 | GSE205174 | GEO
Project description:β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. Here we have used pharmacological inhibitors and a novel direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in brown adipocytes. We show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on brown adipocyte transcription and function.
2022-06-03 | GSE205134 | 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: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