cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.25575185
title: Developmental changes in nuclear lamina components during germ cell differentiation

description: The nuclear lamina (NL) changes composition for regulation of nuclear events. We investigated changes that occur in Drosophila oogenesis, revealing switches in NL composition during germ cell differentiation. Germline stem cells (GSCs) express only LamB and predominantly emerin, whereas differentiating nurse cells predominantly express LamC and emerin2. A change in LamC-specific localization also occurs, wherein phosphorylated LamC redistributes to the nuclear interior only in the oocyte, prior to transcriptional reactivation of the meiotic genome. These changes support existing concepts that LamC promotes differentiation, a premise that was tested. Remarkably ectopic LamC production in GSCs did not promote premature differentiation. Increased LamC levels in differentiating germ cells altered internal nuclear structure, increased RNA production, and reduced female fertility due to defects in eggshell formation. These studies suggest differences between Drosophila lamins are regulatory, not functional, and reveal an unexpected robustness to level changes of a major scaffolding component of the NL.
DOI: 10.6084/m9.figshare.25575185.v1
title: Developmental changes in nuclear lamina components during germ cell differentiation

description: The nuclear lamina (NL) changes composition for regulation of nuclear events. We investigated changes that occur in Drosophila oogenesis, revealing switches in NL composition during germ cell differentiation. Germline stem cells (GSCs) express only LamB and predominantly emerin, whereas differentiating nurse cells predominantly express LamC and emerin2. A change in LamC-specific localization also occurs, wherein phosphorylated LamC redistributes to the nuclear interior only in the oocyte, prior to transcriptional reactivation of the meiotic genome. These changes support existing concepts that LamC promotes differentiation, a premise that was tested. Remarkably ectopic LamC production in GSCs did not promote premature differentiation. Increased LamC levels in differentiating germ cells altered internal nuclear structure, increased RNA production, and reduced female fertility due to defects in eggshell formation. These studies suggest differences between Drosophila lamins are regulatory, not functional, and reveal an unexpected robustness to level changes of a major scaffolding component of the NL.
DOI: 10.6084/m9.figshare.26789558
title: Low circulating levels of neuregulin 4 as a potential biomarker associated with the severity and prognosis of obesity-related metabolic diseases: a systematic review

description: Neuregulin 4 (Nrg4) is a brown adipose tissue-derived adipokine that greatly affects systemic metabolism and improves metabolic derangements. Although abnormal circulating levels of Nrg4 are common in obesity, it remains elusive whether low or elevated levels of this batokine are associated with the onset of metabolic diseases. To assess Nrg4 levels and its role as a feasible biomarker to predict the severity of obesity, gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). A search for relevant studies was performed systematically using prominent search engines, including PubMed, Google Scholar, and Embase, by following PRISMA guidelines. Ample clinical evidence reported low serum/plasma levels of Nrg4 in obesity and these were inversely proportional to the indices of metabolic syndrome, including body mass index, waist circumference, triglycerides, fasting plasma glucose, and homoeostatic model assessment for insulin resistance as well as high-sensitivity C-reactive protein. Low circulating Nrg4 levels may aid in the prediction of morbid obesity, and subsequent GDM, T2DM, NAFLD, and CVD. Current clinical evidence emphasizes that the circulating levels of Nrg4 are decreased in morbid obesity, and it also highlights that Nrg4 May serve as a potential prognostic biomarker for obesity-related metabolic diseases.
DOI: 10.6084/m9.figshare.26789558.v1
title: Low circulating levels of neuregulin 4 as a potential biomarker associated with the severity and prognosis of obesity-related metabolic diseases: a systematic review

description: Neuregulin 4 (Nrg4) is a brown adipose tissue-derived adipokine that greatly affects systemic metabolism and improves metabolic derangements. Although abnormal circulating levels of Nrg4 are common in obesity, it remains elusive whether low or elevated levels of this batokine are associated with the onset of metabolic diseases. To assess Nrg4 levels and its role as a feasible biomarker to predict the severity of obesity, gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). A search for relevant studies was performed systematically using prominent search engines, including PubMed, Google Scholar, and Embase, by following PRISMA guidelines. Ample clinical evidence reported low serum/plasma levels of Nrg4 in obesity and these were inversely proportional to the indices of metabolic syndrome, including body mass index, waist circumference, triglycerides, fasting plasma glucose, and homoeostatic model assessment for insulin resistance as well as high-sensitivity C-reactive protein. Low circulating Nrg4 levels may aid in the prediction of morbid obesity, and subsequent GDM, T2DM, NAFLD, and CVD. Current clinical evidence emphasizes that the circulating levels of Nrg4 are decreased in morbid obesity, and it also highlights that Nrg4 May serve as a potential prognostic biomarker for obesity-related metabolic diseases.
DOI: 10.6084/m9.figshare.27980365
title: The early transition to cold-induced browning in mouse subcutaneous white adipose tissue (scWAT) involves proteins related to nerve remodeling, cytoskeleton, mitochondria, and immune cells

description: White adipose tissue (WAT) is a dynamic organ capable of remodelling in response to metabolic state. For example, in response to stimuli such as cold exposure, WAT can develop inducible brown adipocytes (‘browning’) capable of non-shivering thermogenesis, through concurrent changes to mitochondrial content and function. This is aided by increased neurite outgrowth and angiogenesis across the tissue, providing the needed neurovascular supply for uncoupling protein 1 activation. While several RNA-sequencing studies have been performed in WAT, including newer single cell and single nuclei studies, little work has been done to investigate changes to the adipose proteome, particularly during dynamic periods of tissue remodelling such as cold stimulation. Here, we conducted a comprehensive proteomic analysis of inguinal subcutaneous (sc) WAT during the initial ‘browning’ period of 24 or 72hrs of cold exposure in mice. We identified four significant pathways impacted by cold stimulation that are involved in tissue remodelling, which included mitochondrial function and metabolism, cytoskeletal remodelling, the immune response, and the nervous system. Taken together, we found that early changes in the proteome of WAT with cold stimulation predicted later structural and functional changes in the tissue that are important for tissue and whole-body remodelling to meet energetic and metabolic needs.
DOI: 10.6084/m9.figshare.27980365.v1
title: The early transition to cold-induced browning in mouse subcutaneous white adipose tissue (scWAT) involves proteins related to nerve remodeling, cytoskeleton, mitochondria, and immune cells

description: White adipose tissue (WAT) is a dynamic organ capable of remodelling in response to metabolic state. For example, in response to stimuli such as cold exposure, WAT can develop inducible brown adipocytes (‘browning’) capable of non-shivering thermogenesis, through concurrent changes to mitochondrial content and function. This is aided by increased neurite outgrowth and angiogenesis across the tissue, providing the needed neurovascular supply for uncoupling protein 1 activation. While several RNA-sequencing studies have been performed in WAT, including newer single cell and single nuclei studies, little work has been done to investigate changes to the adipose proteome, particularly during dynamic periods of tissue remodelling such as cold stimulation. Here, we conducted a comprehensive proteomic analysis of inguinal subcutaneous (sc) WAT during the initial ‘browning’ period of 24 or 72hrs of cold exposure in mice. We identified four significant pathways impacted by cold stimulation that are involved in tissue remodelling, which included mitochondrial function and metabolism, cytoskeletal remodelling, the immune response, and the nervous system. Taken together, we found that early changes in the proteome of WAT with cold stimulation predicted later structural and functional changes in the tissue that are important for tissue and whole-body remodelling to meet energetic and metabolic needs.
DOI: 10.6084/m9.figshare.27247281
title: An improved <i>in vitro</i> 3T3-L1 adipocyte model of inflammation and insulin resistance

description: Tumor necrosis factor alpha (TNF-α)/hypoxia-treated 3T3-L1 adipocytes have been used to model inflamed and insulin-resistant adipose tissue: this study examines gaps in the model. We tested whether modulating TNF-α/hypoxia treatment time could reduce cell death while still inducing inflammation and insulin resistance. Adipocytes were treated with TNF-α (12 h or 24 h) and incubated in a hypoxic chamber for 24 h. To examine maintenance of the phenotype over time, glucose and FBS were added at 24 h post initiation of treatment, and the cells were maintained for an additional 48 h. Untreated adipocytes were used as a control. Viability, insulin resistance, and inflammation were assessed using Live/Dead staining, RT-qPCR, ELISA, and glucose uptake assays. Treatment for 12 h with TNF-α in the presence of hypoxia resulted in an increase in the percentage of live cells compared to 24 h treated cells. Importantly, insulin resistance and inflammation were still induced in the 12 h treated adipocytes: the expression of the insulin sensitive and inflammatory genes was decreased and increased, respectively. In 72 h treated adipocytes, no significant differences were found in the viability, glucose uptake or insulin-sensitive and inflammatory gene expression. This study provides a modified approach to in vitro odeling adipocyte inflammation and insulin resistance.
DOI: 10.6084/m9.figshare.27247281.v1
title: An improved <i>in vitro</i> 3T3-L1 adipocyte model of inflammation and insulin resistance

description: Tumor necrosis factor alpha (TNF-α)/hypoxia-treated 3T3-L1 adipocytes have been used to model inflamed and insulin-resistant adipose tissue: this study examines gaps in the model. We tested whether modulating TNF-α/hypoxia treatment time could reduce cell death while still inducing inflammation and insulin resistance. Adipocytes were treated with TNF-α (12 h or 24 h) and incubated in a hypoxic chamber for 24 h. To examine maintenance of the phenotype over time, glucose and FBS were added at 24 h post initiation of treatment, and the cells were maintained for an additional 48 h. Untreated adipocytes were used as a control. Viability, insulin resistance, and inflammation were assessed using Live/Dead staining, RT-qPCR, ELISA, and glucose uptake assays. Treatment for 12 h with TNF-α in the presence of hypoxia resulted in an increase in the percentage of live cells compared to 24 h treated cells. Importantly, insulin resistance and inflammation were still induced in the 12 h treated adipocytes: the expression of the insulin sensitive and inflammatory genes was decreased and increased, respectively. In 72 h treated adipocytes, no significant differences were found in the viability, glucose uptake or insulin-sensitive and inflammatory gene expression. This study provides a modified approach to in vitro odeling adipocyte inflammation and insulin resistance.
DOI: 10.6084/m9.figshare.27986559
title: Follistatin like-1 (<i>Fstl1</i>) regulates adipose tissue development in zebrafish

description: Obesity is a highly prevalent disorder with complex aetiology. Therefore, studying its associated cellular and molecular pathways may be aided by analysing genetic tractable diseases. In this context, the study of ciliopathies such as Bardet–Biedl syndrome has highlighted the relevance of primary cilia in obesity, both in the central nervous system and peripheral tissues. Based on our previous <i>in vitro</i> results supporting the role of a novel Bbs4-cilia-Fstl1 axis in adipocyte differentiation, we evaluated the <i>in vivo</i> relevance of the zebrafish orthologous genes <i>fstl1a</i> and <i>fstl1b</i> in primary cilia and adipose tissue development. Using a combination of knockdowns and a new <i>fstl1a</i> mutant line, we show that <i>fstl1a</i> promotes primary cilia formation in early embryos and participates in adipose tissue formation in larvae. We also show that <i>fstl1b</i> partially compensates for the loss of <i>fstl1a</i>. Moreover, in high fat diet, <i>fstl1a</i> depletion affects the expression of differentiation and mature adipocyte markers. These results agree with our previous <i>in vitro</i> data and provide further support for the role of FSTL1 as a regulator of adipose tissue formation. Dissecting the exact biological role of proteins such as FSTL1 will likely contribute to understand obesity onset and presentation.
DOI: 10.6084/m9.figshare.27986559.v1
title: Follistatin like-1 (<i>Fstl1</i>) regulates adipose tissue development in zebrafish

description: Obesity is a highly prevalent disorder with complex aetiology. Therefore, studying its associated cellular and molecular pathways may be aided by analysing genetic tractable diseases. In this context, the study of ciliopathies such as Bardet–Biedl syndrome has highlighted the relevance of primary cilia in obesity, both in the central nervous system and peripheral tissues. Based on our previous <i>in vitro</i> results supporting the role of a novel Bbs4-cilia-Fstl1 axis in adipocyte differentiation, we evaluated the <i>in vivo</i> relevance of the zebrafish orthologous genes <i>fstl1a</i> and <i>fstl1b</i> in primary cilia and adipose tissue development. Using a combination of knockdowns and a new <i>fstl1a</i> mutant line, we show that <i>fstl1a</i> promotes primary cilia formation in early embryos and participates in adipose tissue formation in larvae. We also show that <i>fstl1b</i> partially compensates for the loss of <i>fstl1a</i>. Moreover, in high fat diet, <i>fstl1a</i> depletion affects the expression of differentiation and mature adipocyte markers. These results agree with our previous <i>in vitro</i> data and provide further support for the role of FSTL1 as a regulator of adipose tissue formation. Dissecting the exact biological role of proteins such as FSTL1 will likely contribute to understand obesity onset and presentation.
DOI: 10.6084/m9.figshare.25959188
title: Comparison of stromal vascular fraction cell composition between Coleman fat and extracellular matrix/stromal vascular fraction gel

description: As a mechanically condensed product of Coleman fat, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) eliminates adipocytes, concentrates SVF cells, and improves fat graft retention. This study aims to compare SVF cell composition between Coleman fat and ECM/SVF-gel. Matched Coleman fat and ECM/SVF-gel of 28 healthy women were subjected to RNA-seq, followed by functional enrichment and cell-type-specific enrichment analyses, and deconvolution of SVF cell subsets, reconstructing SVF cell composition in the transcriptome level. ECM/SVF-gels had 9 upregulated and 73 downregulated differentially expressed genes (DEGs). Downregulated DEGs were mainly associated with inflammatory and immune responses, and enriched in fat macrophages. M2 macrophages, resting CD4<sup>+</sup> memory T cells, M1 macrophages, resting mast cells, and M0 macrophages ranked in the top five most prevalent immune cells in the two groups. The proportions of the principal non-immune cells (e.g., adipose-derived stem cells, pericytes, preadipocytes, microvascular endothelial cells) had no statistical differences between the two groups. Our findings reveal ECM/SVF-gels share the same dominant immune cells beneficial to fat graft survival with Coleman fat, but exhibiting obvious losses of immune cells (especially macrophages), while non-immune cells necessary for adipose regeneration might have no significant loss in ECM/SVF-gels and their biological effects could be markedly enhanced by the ECM/SVF-gel’s condensed nature.
DOI: 10.6084/m9.figshare.25959188.v1
title: Comparison of stromal vascular fraction cell composition between Coleman fat and extracellular matrix/stromal vascular fraction gel

description: As a mechanically condensed product of Coleman fat, extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) eliminates adipocytes, concentrates SVF cells, and improves fat graft retention. This study aims to compare SVF cell composition between Coleman fat and ECM/SVF-gel. Matched Coleman fat and ECM/SVF-gel of 28 healthy women were subjected to RNA-seq, followed by functional enrichment and cell-type-specific enrichment analyses, and deconvolution of SVF cell subsets, reconstructing SVF cell composition in the transcriptome level. ECM/SVF-gels had 9 upregulated and 73 downregulated differentially expressed genes (DEGs). Downregulated DEGs were mainly associated with inflammatory and immune responses, and enriched in fat macrophages. M2 macrophages, resting CD4<sup>+</sup> memory T cells, M1 macrophages, resting mast cells, and M0 macrophages ranked in the top five most prevalent immune cells in the two groups. The proportions of the principal non-immune cells (e.g., adipose-derived stem cells, pericytes, preadipocytes, microvascular endothelial cells) had no statistical differences between the two groups. Our findings reveal ECM/SVF-gels share the same dominant immune cells beneficial to fat graft survival with Coleman fat, but exhibiting obvious losses of immune cells (especially macrophages), while non-immune cells necessary for adipose regeneration might have no significant loss in ECM/SVF-gels and their biological effects could be markedly enhanced by the ECM/SVF-gel’s condensed nature.
DOI: 10.6084/m9.figshare.26311094
title: Association between the triglyceride glucose index and short-term mortality in septic patients with or without obesity: a retrospective cohort study

description: Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients. This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis. 8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76–9.71) vs. 9.10(8.67–9.54), <i>p</i> &lt; 0.001]. The adjusted multivariate regression model showed that elevated TyGI values were linked to a greater likelihood of death in ICU (odds ratio [OR] range 1.072–1.793, <i>p</i> &lt; 0.001) and hospital (OR range 1.068–1.445, <i>p</i> = 0.005). Restricted Cubic Spline analysis revealed a nonlinear association between TyGI and in-ICU and in-hospital mortality risks within specified ranges. Subgroup analysis revealed interaction effects in the general obesity, abdominal obesity, and impaired fasting glucose subgroups (<i>p</i> = 0.014, 0.016, and &lt; 0.001, respectively). TyGI was associated with an increased sepsis-related short-term mortality risk and adverse outcomes after ICU admission.
DOI: 10.6084/m9.figshare.26311094.v1
title: Association between the triglyceride glucose index and short-term mortality in septic patients with or without obesity: a retrospective cohort study

description: Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients. This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis. 8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76–9.71) vs. 9.10(8.67–9.54), <i>p</i> &lt; 0.001]. The adjusted multivariate regression model showed that elevated TyGI values were linked to a greater likelihood of death in ICU (odds ratio [OR] range 1.072–1.793, <i>p</i> &lt; 0.001) and hospital (OR range 1.068–1.445, <i>p</i> = 0.005). Restricted Cubic Spline analysis revealed a nonlinear association between TyGI and in-ICU and in-hospital mortality risks within specified ranges. Subgroup analysis revealed interaction effects in the general obesity, abdominal obesity, and impaired fasting glucose subgroups (<i>p</i> = 0.014, 0.016, and &lt; 0.001, respectively). TyGI was associated with an increased sepsis-related short-term mortality risk and adverse outcomes after ICU admission.
DOI: 10.6084/m9.figshare.27443729
title: Lipid accumulation in adipose tissue-resident iNKT cells contributes to an inflammatory phenotype

description: Reciprocal communication between adipocytes and immune cells is essential to maintain optimal adipose tissue (AT) functionality. Amongst others, adipocytes directly interact with invariant NKT cells (iNKT cells), which in turn secrete various cytokines. A lipid-rich microenvironment, as observed in obesity, skews this adipocyte-driven cytokine output towards a more inflammatory output. Whether a lipid-rich microenvironment also affects iNKT cells directly, however, is unknown. Here, we show that primary mouse iNKT cells isolated from AT can accumulate lipids in lipid droplets (LDs), more so than liver- and spleen-resident iNKT cells. Furthermore, a lipid-rich microenvironment increased the production of the proinflammatory cytokine IFNγ. Next, to an indirect, adipocyte-mediated cue, iNKT cells can directly respond to environmental lipid changes, supporting a potential role as nutrient sensors.
DOI: 10.6084/m9.figshare.27443729.v1
title: Lipid accumulation in adipose tissue-resident iNKT cells contributes to an inflammatory phenotype

description: Reciprocal communication between adipocytes and immune cells is essential to maintain optimal adipose tissue (AT) functionality. Amongst others, adipocytes directly interact with invariant NKT cells (iNKT cells), which in turn secrete various cytokines. A lipid-rich microenvironment, as observed in obesity, skews this adipocyte-driven cytokine output towards a more inflammatory output. Whether a lipid-rich microenvironment also affects iNKT cells directly, however, is unknown. Here, we show that primary mouse iNKT cells isolated from AT can accumulate lipids in lipid droplets (LDs), more so than liver- and spleen-resident iNKT cells. Furthermore, a lipid-rich microenvironment increased the production of the proinflammatory cytokine IFNγ. Next, to an indirect, adipocyte-mediated cue, iNKT cells can directly respond to environmental lipid changes, supporting a potential role as nutrient sensors.