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The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiation.

OBJECTIVE: Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder featuring near complete absence of adipose tiss … using short hairpin RNA (shRNA). These cells were used to investigate whether BSCL2 is required for adipogenesis. BSCL2 constructs harboring pathogenic mutations known to cause lipodystrophy were also generated and characterized. RESULTS: BSCL2 expression was strongly induced during adipocyte differentiation, and the induction of BSCL2 expression was essentia …

Increasing local adipogenic signaling through cutaneous delivery of rosiglitazone decreases fibrosis in secondary lymphedema.

BACKGROUND: Secondary lymphedema is a common, debilitating consequence of oncologic surgery that leads to irreversible skin and subcutaneous fibrosis. No topical anti-fibrotic therapy currently exists. We previously showed that systemic rosiglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) agonist, promotes adipogenesis and reduces fibrosis in experimental lymphedema, but systemic toxicity limits its use. METHODS: A murine tail model of secondary lymphedema was used to compare systemic and topical rosiglitazone. scRNA-seq data was initially used to justify interrogation of ros…

An ovine model shows that subcutaneous adipose tissue fibrosis occurs early in polycystic ovary syndrome (PCOS).

Prenatally androgenised (PA) sheep are a clinically realistic model of polycystic ovary syndrome (PCOS). They have dysfunctional subcutaneous adipose tissue (SAT) with reduced adipogenesis in adolescence and enlarged adipocytes with increased inflammation in adulthood. We hypothesised that analysis of SAT in young adults, after adipogenesis is complete but before inflammation is apparent, would give insights into the evolution of adipose tissue dysfunction. Pregnant sheep were treated intramuscularly with 100 mg testosterone propionate or vehicle control (C) twice weekly from day 62-102 of ges…

Current Applications and Indications of Allograft Adipose Matrix: A Systematic Review.

BACKGROUND: Autologous fat transfer remains a staple in aesthetic and reconstructive surgery because of its regenerative capacity and tissue integration. However, limitations such as donor-site morbidity and unpredictable volume retention persist. Allograft adipose matrix (AAM), a product made from human fat tissue that serves as a natural scaffold to promote adipogenesis, offers a promising alternative, serving as a scaffold for adipogenesis and delivering key extracellular matrix components. This review examines clinical applications and outcomes in soft-tissue augmentation. METHODS: A syst…

Anti-obesity effects of Celosia cristata flower extract in vitro and in vivo.

BACKGROUND: The overstoring of surplus calories in mature adipocytes causes obesity and abnormal metabolic activity. The anti-obesity effect of a Celosia cristata (CC) total flower extract was assessed in vitro, using 3T3-L1 pre-adipocytes and mouse adipose-derived stem cells (ADSCs), and in vivo, using high-fat diet (HFD)-treated C57BL/6 male mice. METHODS: CC extract was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs. After differentiation, lipid droplets were assessed by oil red O staining, adipogenesis and lipolytic factors were evaluated, and intracellular triglyceride a…

Therapeutic of a white adipose tissue-specific bivalent aptamer in obesity.

The white adipose tissue-specific aptamer Adipo8 can specificity bindwith mature adipocytes or tissues and inhibit adipogenesis.In this research, we exploredthe effect of Adipo8 intervention on the transcriptome in the process of adipogenesis using mRNA-level sequencing,analyzed the mechanism ofAdipo8 ininhibiting adipogenesis. The results showed that Adipo8 can inhibit lipid formation and downregulate PPARγ and C/EBPα in differentiated 3 T3-L1 cells. Transcriptome mRNA sequencing of 3 T3-L1 cells after Adipo8 interventionrevealed that Adipo8 might inhibit the biological function of adipogenes…

Терапевтический потенциал диметилФумарата для обработки высококалорийной/высокосортной диетологической ожиренией.

Ожирение характеризуется несбалансированностью между потреблением энергии и расходами, которая вызывает ненормальный рост жировых тканей. Диметилфумарат (ДМП) и его первичный активный метаболит монометилфумарат (ММФ) являются активаторами Nrf2 и признаны в качестве стратегических антиоксидантов. Цель этого исследования состояла в том, чтобы оценить потенциал MMF и DMF в плане воздействия на адипогенез и ожирение, а также выявить соответствующие молекулярные механизмы. Предадипоциты 3T3-L1 были инкубированы с дифференциальной среды (MIX) и одновременно обработаны различными концентрациями MMF.

Совпадение в аннотации оригинала
Obesity is characterized by an imbalance between energy intake and expenditure that triggers abnormal growth of adipose tissues. Dimethyl fu … strategic antioxidants. This study aimed to evaluate the potential of MMF and DMF to interfere with adipogenesis and obesity, and identify the molecular mechanisms involved. The 3T3-L1 preadipocytes were incubated with differentiation medium (MIX) and simultaneously treated with different concentrations of MMF. In addition, male C57BL/6 mice were fed a standar …

Increased BMPR1A Expression Enhances the Adipogenic Differentiation of Mesenchymal Stem Cells in Patients with Ankylosing Spondylitis.

OBJECTIVE: To investigate the adipogenic differentiation capacity of mesenchymal stem cells (MSCs) from ankylosing spondylitis (AS) patients and explore the mechanism of abnormal MSC adipogenesis in AS. METHODS: MSCs from patients with AS (ASMSCs) and healthy donors (HDMSCs) were cultured in adipogenic differentiation medium for up to 21 days. Adipogenic differentiation was determined using oil red O (ORO) staining and quantification and was confirmed by assessing adipogenic marker expression (PPAR-γ, FABP4, and adiponectin). Gene expression of adipogenic markers was detected using qRT-PCR. P…

A novel bone targeting delivery system carrying phytomolecule icaritin for prevention of steroid-associated osteonecrosis in rats.

One of the effective strategies for prevention of steroid-associated osteonecrosis (SAON) is to inhibit bone resorption and fat formation and promote bone formation at osteonecrotic sensitive skeletal sites. We identified a novel phytomolecule that showed positive effects on osteogenesis, anti-bone resorption and anti-adipogenesis in vitro and also developed a bone-targeting delivery system (BTDS) for in vivo experimental study. The study investigated if our innovative synthesized BTDS carrying this phytomolecule would be able to effectively prevent SAON in a rat model. SAON was induced by com…

Aloe-Emodin Modifies Adipogenic Genes and the Expression of miR-143 and miR-155 in 3T3-L1 Cells.

Adipogenesis is crucial for maintaining energy homeostasis, as it facilitates the differentiation of mesenchymal stem cells into adipocytes. This process is transcriptionally regulated by key factors including PPARγ and C/EBPβ, alongside FABP4 during lipogenesis. However, it is now well established that a significant portion of this regulation is also mediated by small non-coding RNAs (miRNAs) and long non-coding RNAs (lncRNAs), which post-transcriptionally modulate gene expression. This study aimed to identify key miRNAs involved in adipogenesis and to determine how Aloe-emodin, a molecule wi…

Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function.

The epigenetic mechanisms regulating adipose tissue development and function are poorly understood. In this study, we show that depletion of histone H3K36 methylation by H3.3K36M in preadipocytes inhibits adipogenesis by increasing H3K27me3 to prevent the induction of C/EBPα and other targets of the master adipogenic transcription factor peroxisome proliferator-activated receptor-γ (PPARγ). Depleting H3K36 methyltransferase Nsd2, but not Nsd1 or Setd2, phenocopies the effects of H3.3K36M on adipogenesis and PPARγ target expression. Consistently, expression of H3.3K36M in progenitor cells impai…

Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins.

Sirt1 is an NAD+-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD's ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site. ATP, but not NAD+, causes a conformational shift to a less comp…

Nonylphenol-induced hyperadrenalism can be reversed/alleviated by inhibiting of 11-β hydroxysteroid dehydrogenase type 1.

We previously observed that nonylphenol (NP) exposure during development resulted in increases in body weight and hyperadrenalism in adult male offspring. The mechanism of hyperadrenalism includes the primary activation of the adrenal gland and the conversion of inactive glucocorticoids to active glucocorticoids by 11β-HSD1. The inhibition of 11β-HSD1 is investigated as a new therapeutic approach. This study examined the effect of PF915275 (a selective 11β-HSD1 inhibitor) on hyperadrenalism and adipogenesis in male rats exposed to NP during development. The results showed that treatment with t…

Inhibition of dipeptidyl peptidase 8/9 impairs preadipocyte differentiation.

Adipocytes are the primary cells in adipose tissue, and adipocyte dysfunction causes lipodystrophy, obesity and diabetes. The dipeptidyl peptidase (DPP) 4 family includes four enzymes, DPP4, DPP8, DPP9 and fibroblast activation protein (FAP). DPP4 family inhibitors have been used for the treatment of type 2 diabetes patients, but their role in adipocyte formation are poorly understood. Here we demonstrate that the DPP8/9 selective inhibitor 1G244 blocks adipogenesis in preadipocyte 3T3-L1 and 3T3-F422A, while DPP4 and FAP inhibitors have no effect. In addition, knockdown of DPP8 or DPP9 signif…

The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1.

Disruption of the gene BSCL2 causes a severe, generalised lipodystrophy, demonstrating the critical role of its protein product, seipin, in human adipose tissue development. Seipin is essential for adipocyte differentiation, whilst the study of seipin in non-adipose cells has suggested a role in lipid droplet formation. However, its precise molecular function remains poorly understood. Here we demonstrate that seipin can inducibly bind lipin 1, a phosphatidic acid (PA) phosphatase important for lipid synthesis and adipogenesis. Knockdown of seipin during early adipogenesis decreases the associ…

Insights into the effects of sex and tissue location on the evolution of adipocyte dysfunction in an ovine model of polycystic ovary syndrome (PCOS).

Adipose tissue dysfunction is one of the features of Polycystic Ovary Syndrome (PCOS) with dysregulated adipogenesis, altered functional pathways and increased inflammation. It is increasingly clear that there are also male correlates of the hormonal and metabolic features of PCOS. We hypothesised that the effects of adipose tissue dysfunction are not sex-specific but rather fat depot-specific and independent of obesity. We used a clinically realistic ovine model of PCOS where pregnant sheep are injected with 100 mg of testosterone propionate twice weekly from day 62 to day 102 of gestation. W…

Simultaneous Effects of a Selective EP2 Agonist, Omidenepag, and a Rho-Associated Coiled-Coil Containing Protein Kinase Inhibitor, Ripasudil, on Human Orbital Fibroblasts.

Purpose: To assess the combined effects of omidenepag (OMD), a selective EP2 agonist, and ripasudil (Rip), an inhibitor of rho-associated coiled-coil containing protein kinases, on the human orbital adipose tissue, two-dimensional (2D) or three-dimensional (3D) cultures of human orbital fibroblasts (HOFs) were employed. Methods: Cellular metabolic functions (2D), physical (3D), lipid staining (3D), and quantitative polymerase chain reaction for adipogenesis-related genes, PPARγ and AP2, and extracellular matrix (ECM) molecules, including collagen (COL)1, 4, and 6, and fibronectin (FN) (3D) wer…

Fibroadipogenic progenitors are responsible for muscle loss in limb girdle muscular dystrophy 2B.

Muscle loss due to fibrotic or adipogenic replacement of myofibers is common in muscle diseases and muscle-resident fibro/adipogenic precurs … nxA2) in the myofiber matrix causes FAP differentiation into adipocytes. Lack of AnxA2 prevents FAP adipogenesis, protecting against adipogenic loss of dysferlinopathic muscle while exogenous AnxA2 enhances muscle loss. Pharmacological inhibition of FAP adipogenesis arrests adipogenic replacement and degeneration of dysferlin-deficient muscle. These results de …

Fibroblast growth factor 8b induces uncoupling protein 1 expression in epididymal white preadipocytes.

The number of brown adipocytes residing within murine white fat depots (brite adipocytes) varies a lot by depot, strain and physiological condition. Several endocrine fibroblast growth factors are implicated in the regulation of brite adipocyte abundance. The family of fibroblast growth factors can be categorized by their site of action into endocrine, paracrine and intracellular peptides. We here screened paracrine fibroblast growth factors for their potential to drive brite adipogenesis in differentiating epididymal white adipocytes and identified fibroblast growth factor 8b to induce uncoup…

Integrative Transcriptomics and Proteomics Analysis Reveals THRSP's Role in Lipid Metabolism.

Background/Objectives: Abnormalities in lipid metabolism and endoplasmic reticulum (ER) stress are strongly associated with the development of a multitude of pathological conditions, including nonalcoholic fatty liver disease (NAFLD), diabetes mellitus, and obesity. Previous studies have indicated a potential connection between thyroid hormone responsive (THRSP) and lipid metabolism and that ER stress may participate in the synthesis of key regulators of adipogenesis. However, the specific mechanisms remain to be investigated. Methods: In this study, we explored the roles of THRSP in lipid met…