Maternal Brown Fat Thermogenesis Programs Glucose Tolerance in the Male Offspring
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ABSTRACT:
PROVIDER: PRJNA606192 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We tested if minor changes in maternal non-shivering thermogenesis during pregnancy can severely alter the phenotype of the offspring already in the next generation. Therefore, male offspring of dams lacking the uncoupling protein 1 (UCP1-KO) in the thermogenic brown adipose tissue were analysed. Genome-wide expression profiling identified several alterations in the hepatic transcriptomic landscape, demonstrating that even minor differences in the demand for maternal thermogenesis profoundly and permanently alter hepatic gene activity in the adult offspring. Liver gene expression data of offspring from WT and UCP1-KO dams.
2020-11-09 | GSE145143 | GEO
Project description:We tested if minor changes in environmental temperature during pregnancy can severely alter the phenotype of the offspring already in the next generation. Genome-wide expression profiling of liver samples obtained from adult male mice offspring identified several alterations in the hepatic transcriptomic landscape, thus demonstrating that even minor differences in the demand for maternal thermogenesis profoundly and permanently alter hepatic gene activity in the adult offspring. Liver gene expression data of offspring from dams that were kept at different ambient temperatures (30°C, 23°C, 18°C, 10°C) only during pregnancy.
2020-11-09 | GSE145142 | GEO
Project description:Maternal Brown Fat Thermogenesis Programs Glucose Tolerance in the Male Offspring
| PRJNA606193 | ENA
Project description:Metabolomics dataset of serum from T3-treated dams. Related to following publication by Oelkrug et al: "Maternal thyroid hormone receptor beta activation sparks brown fat thermogenesis in the offspring"
2023-01-11 | MSV000091042 | GNPS
Project description:Brown adipose tissue (BAT) is best known for thermogenesis. Whereas numerous studies in rodents found tight associations between the metabolic benefits of BAT and enhanced whole-body energy expenditure, emerging evidence in humans suggests that BAT is protective against Type 2 diabetes independent of body-weight. The underlying mechanism for this dissociation remained unclear. Here, we report that impaired mitochondrial flux of branched-chain amino acids (BCAA) in BAT, by deleting mitochondrial BCAA carrier (MBC, encoded by Slc25a44), was sufficient to cause systemic insulin resistance without affecting whole-body energy expenditure or body-weight. We found that brown adipocytes catabolized BCAAs in the mitochondria as essential nitrogen donors for the biosynthesis of glutamate, N-acetylated amino acids, and one of the products, glutathione. BAT-selective impairment in mitochondrial BCAA flux led to elevated oxidative stress and insulin resistance in the liver, accompanied by reduced levels of BCAA-nitrogen derived metabolites in the circulation. In turn, supplementation of glutathione restored insulin sensitivity of BAT-specific MBC knockout mice. Notably, a high-fat diet rapidly impaired BCAA catabolism and the synthesis of BCAA-nitrogen derived metabolites in the BAT, while cold-induced BAT activity is coupled with an active synthesis of these metabolites. Together, the present work uncovers a mechanism through which brown fat controls metabolic health independent of thermogenesis via BCAA-derived nitrogen carriers acting on the liver.
2024-02-15 | PXD044020 | Pride
Project description:Brown adipose tissue (BAT) is best known for thermogenesis. Whereas numerous studies in rodents found tight associations between the metabolic benefits of BAT and enhanced whole-body energy expenditure, emerging evidence in humans suggests that BAT is protective against Type 2 diabetes independent of body-weight. The underlying mechanism for this dissociation remained unclear. Here, we report that impaired mitochondrial flux of branched-chain amino acids (BCAA) in BAT, by deleting mitochondrial BCAA carrier (MBC, encoded by Slc25a44), was sufficient to cause systemic insulin resistance without affecting whole-body energy expenditure or body-weight. We found that brown adipocytes catabolized BCAAs in the mitochondria as essential nitrogen donors for the biosynthesis of glutamate, N-acetylated amino acids, and one of the products, glutathione. BAT-selective impairment in mitochondrial BCAA flux led to elevated oxidative stress and insulin resistance in the liver, accompanied by reduced levels of BCAA-nitrogen derived metabolites in the circulation. In turn, supplementation of glutathione restored insulin sensitivity of BAT-specific MBC knockout mice. Notably, a high-fat diet rapidly impaired BCAA catabolism and the synthesis of BCAA-nitrogen derived metabolites in the BAT, while cold-induced BAT activity is coupled with an active synthesis of these metabolites. Together, the present work uncovers a mechanism through which brown fat controls metabolic health independent of thermogenesis via BCAA-derived nitrogen carriers acting on the liver.
2024-02-15 | PXD043992 | Pride
Project description:Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression in brown and beige adipocytes and that SUV420H2 knockdown significantly reduces, whereas SUV420H2 overexpression significantly increases UCP1 levels in brown adipocytes. Suv420h2 knockout (H2KO mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study showed that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) promoter, leading to down-regulated expression of 4E-BP1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.
2024-05-09 | GSE244457 | GEO
Project description:The defective activity of brown adipose tissue (BAT) is linked to obesity and cardiometabolic diseases. While there is extensive knowledge about the biological signals that trigger BAT thermogenesis, information regarding active repressors that may contribute to the pathological impairment of BAT function is quite limited. Acyl CoA-Binding Protein (ACBP), also known as Diazepam Binding Inhibitor (DBI), is a protein with intracellular functions related to lipid metabolism. It can also be secreted and act as a circulating regulatory factor that affects multiple tissues and organs. We discovered that ACBP expression and release in BAT are suppressed by noradrenergic, cAMP-dependent signals that stimulate thermogenesis. This regulation occurs through mechanisms involving gene expression and autophagy-related processes. Mice with targeted ablation of the Acbp gene in brown adipocytes exhibit enhanced BAT thermogenic activity and protection against obesity and glucose intolerance induced by a high-fat diet. This is associated with a remodeling of the BAT transcriptome, characterized by the induction of genes related to BAT thermogenesis. Treatment of brown adipocytes with exogenous ACBP suppressed oxidative activity, lipolysis, and the expression of genes associated with thermogenesis. ACBP inhibits the noradrenergic-induced phosphorylation of p38 MAP kinase and CREB, major intracellular mediators of brown adipocyte thermogenesis. Our findings identify the ACBP system as a crucial auto-regulatory repressor of BAT thermogenesis, which responds reciprocally to the noradrenergic induction of BAT activity.
2025-05-08 | GSE285403 | GEO
Project description:It is well established that maternal thyroid hormones play an important role for the developing fetus; however, the consequences of maternal hyperthyroidism for the offspring remain poorly understood. Here we show in mice that maternal 3,3',5-triiodothyronine (T3) treatment during pregnancy leads to improved glucose tolerance in the adult male offspring and hyperactivity of brown adipose tissue (BAT) thermogenesis in both sexes starting early after birth. The activated BAT provides advantages upon cold exposure, reducing the strain on other thermogenic organs like muscle. This maternal BAT programming requires intact maternal thyroid hormone receptor β (TRβ) signaling, as offspring of mothers lacking this receptor display the opposite phenotype. On the molecular level, we identify distinct T3 induced alterations in maternal serum metabolites, including choline, a key metabolite for healthy pregnancy. Taken together, our results connect maternal TRβ activation to the fetal programming of a thermoregulatory phenotype in the offspring.
| S-EPMC10597992 | biostudies-literature
Project description:The suprachiasmatic nucleus (SCN), the central circadian pacemaker, orchestrates daily metabolic rhythms, yet its role in substrate selection and thermogenic adaptation remains insufficiently understood. Here, we show that SCN lesioning abolishes the adaptive suppression of brown adipose tissue (BAT) thermogenesis typically observed during time-restricted feeding in subthermoneutral environments (TRF-STE), a condition that imposes concurrent nutrient and thermal challenges. Contrary to wild-type responses, SCN-lesioned mice maintain elevated BAT thermogenic activity, driven by enhanced sympathetic tone and β3-adrenergic receptor (ADRB3) signaling. This compensatory response promotes a shift from lipid oxidation to glucose utilization, enabling heat production despite impaired lipolysis. Mechanistically, we identify a SCN-regulated ADRB3-S100B signaling axis underlying this metabolic reprogramming. S100B, a nutrient-sensitive protein calcium-binding protein, is upregulated in BAT following SCN disruption, where it enhances thermogenic capacity by stimulating brown adipocyte proliferation and suppressing senescence. Functional studies reveal that S100B is both necessary and sufficient for sustaining BAT thermogenesis under TRF-STE. Furthermore, diverse SCN disruption models, including light-induced circadian arrhythmia, N - Methyl - D - aspartic acid (NMDA) excitotoxicity, and Caspase-3-mediated ablation, consistently elevates S100B expression in BAT, reinforcing its role as a convergent effector of SCN-regulated metabolic adaptation. These findings uncover a previously unrecognized role of the SCN in coordinating thermogenic flexibility and fuel partitioning under stress. The identification of the ADRB3-S100B axis as a key mediator of this adaptation provides new mechanistic insight into the neural regulation of energy balance, with potential therapeutic relevance for circadian misalignment, obesity, and resistance to diet-induced weight loss.
2025-11-06 | GSE300640 | GEO