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A subpopulation of lipogenic brown adipocytes drives thermogenic memory

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE218711 | GEO | 2023/09/11

REPOSITORIES: GEO

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A subpopulation of lipogenic brown adipocytes drives thermogenic memory [snRNAseq]

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

A subpopulation of lipogenic brown adipocytes drives thermogenic memory [Spatial Transcriptomics]

Project description:Spatial transcriptomics of brown adipose tissue from thermoneutrality (TN) and from mouse that had undergone transient acute cold exposure 4 days previously (1cyc)

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A subpopulation of lipogenic brown adipocytes drives thermogenic memory

Project description:A subpopulation of lipogenic brown adipocytes drives thermogenic memory

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A subpopulation of lipogenic brown adipocytes drives thermogenic memory [snRNAseq]

Project description:A subpopulation of lipogenic brown adipocytes drives thermogenic memory [snRNAseq]

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A subpopulation of lipogenic brown adipocytes drives thermogenic memory [Spatial Transcriptomics]

Project description:A subpopulation of lipogenic brown adipocytes drives thermogenic memory [Spatial Transcriptomics]

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Gene expression analysis of directly converted brown adipocytes (dBAs).

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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3-Iodothyronamine Affects Thermogenic Substrates' Mobilization in Brown Adipocytes.

Project description:We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). BAs isolated from the stromal fraction of rat brown adipose tissue were exposed to an adipogenic medium containing insulin in the absence (M) or in the presence of 20 nM T1AM (M+T1AM) for 6 days. At the end of the treatment, the expression of p-PKA/PKA, p-AKT/AKT, p-AMPK/AMPK, p-CREB/CREB, p-P38/P38, type 1 and 3 beta adrenergic receptors (?1-?3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated. The effects of cell conditioning with T1AM on fatty acid mobilization (basal and adrenergic-mediated), glucose uptake (basal and insulin-mediated), and ATP cell content were also analyzed in both cell populations. When compared to cells not exposed, M+T1AM cells showed increased p-PKA/PKA, p-AKT/AKT, p-CREB/CREB, p-P38/P38, and p-AMPK/AMPK, downregulation of DIO2 and ?1AR, and upregulation of glycosylated ?3AR, GLUT4, and adiponectin. At basal conditions, glycerol release was higher for M+T1AM cells than M cells, without any significant differences in basal glucose uptake. Notably, in M+T1AM cells, adrenergic agonists failed to activate PKA and lipolysis and to increase ATP level, but the glucose uptake in response to insulin exposure was more pronounced than in M cells. In conclusion, our results suggest that BAs conditioning with T1AM promote a catabolic condition promising to fight obesity and insulin resistance.

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Shared PPARα/γ target genes regulate brown adipocyte thermogenic function

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-01-30 | GSE144491 | GEO