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Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels.

OBJECTIVE: The expansion of adipose tissue mass seen in obesity involves both hyperplasia and hypertrophy of adipocytes. However, little is known about how adipocytes, adipocyte precursors, blood vessels, and stromal cells interact with one another to achieve adipogenesis. RESEARCH DESIGN AND METHODS: We have developed a confocal microscopy-based method of three-dimensional visualization of intact living adipose tissue that enabled us to simultaneously evaluate angiogenesis and adipogenesis in db/db mice. RESULTS: We found that adipocyte differentiation takes place within cell clusters (whic…

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition.

Experimental and clinical studies have demonstrated that early postnatal overnutrition represents a risk factor for later obesity and associated metabolic and cardiovascular disturbance. In the present study, we assessed the levels of glucose transporter 4 (GLUT-4), GLUT-1, insulin receptor (IR), IR substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt expression, as well as insulin-stimulated glucose transport and Akt activity in adipocytes from adult rats previously raised in small litters (SL). The normal litter (NL) served as control group. We also investigated glycemia, insuli…

Tumor necrosis factor-alpha stimulates HIV-1 production in primary culture of human adipocytes.

Adipose tissue of HIV-1-infected patients shows severe abnormalities such as profound changes in adipose tissue morphology and metabolism. Does HIV-1 infect the adipose cell remains an unsolved question since previous attempts showed that HIV-1 poorly infects human adipocytes in vitro. In the present study, preadipose cells from human subcutaneous fat pads were differentiated in vitro, checked for HIV receptor expression, then infected with R5 and X4 HIV1 strains. Using a sensitive RT-PCR assay, we showed that HIV-1 tat and rev early viral transcripts were expressed in infected adipocytes givi…

Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes.

Aldosterone is a mineralocorticoid hormone that regulates blood pressure and salt/water balance. Increased aldosterone levels are found in states of disturbed energy balance such as the metabolic syndrome. Adipose tissue has been recognized to play a pivotal role in the regulation of energy homeostasis. We investigated direct aldosterone effects on brown adipocyte function. Aldosterone dose-dependently inhibited expression of uncoupling protein-1 (UCP-1) by 30% (p < 0.01). Furthermore, aldosterone dose-dependently impaired insulin-induced glucose uptake by about 25% (p < 0.01). On a transcript

Adipocytes targets and actors in the pathogenesis of HIV-associated lipodystrophy and metabolic alterations.

The recent clinical use of potent HIV-1 drugs, including nucleoside reverse transcriptase inhibitors (NRTIs) and non-peptidic viral protease … HIV drug inhibitory effects on adipocyte differentiation, alteration of mitochondrial functions in adipocytes and altered leptin, adiponectin and cytokine expression in adipose tissue of patients. Adipose tissue may thus be a central regulator in disorganized lipid metabolism and insulin resistance associated with antiretroviral therapy, and we propose in t …

Insulin increases the density of potassium channels in white adipocytes: possible role in adipogenesis.

We studied the potassium currents in white adipocytes obtained by culturing preadipocytes from rat epididymal tissue, both with insulin (WA(i)) and without insulin (WA(o)), in order to test the role of insulin in the development of voltage-gated potassium channels (K(v)) during adipogenesis. Occasionally, very small potassium currents (I(K,V)) were present in preadipocytes; however these currents were measured in all differentiated cells (adipocytes). WA(i) exhibited greater macroscopic potassium currents than WA(o) with no apparent differences in kinetics or voltage dependence. The current de…

Insulin stimulates actin comet tails on intracellular GLUT4-containing compartments in differentiated 3T3L1 adipocytes.

Incubation of isolated GLUT4-containing vesicles with Xenopus oocyte extracts resulted in a guanosine 5'-[gamma-thio]triphosphate (GTP gamma S) and sodium orthovanadate stimulation of actin comet tails. The in vitro actin-based GLUT4 vesicle motility was inhibited by both latrunculin B and a dominant-interfering N-WASP mutant, N-WASP/Delta VCA. Preparations of gently sheared (broken) 3T3L1 adipocytes also displayed GTP gamma S and sodium orthovanadate stimulation of actin comet tails on GLUT4 intracellular compartments. Furthermore, insulin pretreatment of intact adipocytes prior to gently she…

Twf1 regulates adipocyte proliferation and differentiation through Yap nucleus accumulation.

Obesity involves white adipose tissue (WAT) expansion via hyperplasia and hypertrophy. Impaired adipocyte proliferation leads to pathological hypertrophy, inflammation and metabolic dysfunction. Aberrant F‑actin turnover disrupts proliferation/differentiation. Twinfilin‑1 (Twf1) regulates actin dynamics and cell proliferation/differentiation, but its role in adipocytes is unknown. Obese mice were induced by high‑fat diet (HFD) and weight loss by calorie restriction. Inguinal, epididymal and scapular adipose tissues were collected. Proteomics used pressure cycling, DDA library building and DIA …

The Mechanobiology of Adipocyte Hypertrophy: Cytoskeletal Remodelling as a Driver of Insulin Resistance in Obesity.

Adipocyte hypertrophy poses an important mechanical challenge-adipocytes can increase in volume up to a thousand-fold while still maintaining their structural integrity. Although lipid metabolism is well studied, little is known about the cytoskeletal adaptations that are required to accommodate this expansion and the resulting pathological consequences. This review critically examines how the cytoskeletal remodelling is associated with insulin resistance. We explore how mechanotransduction pathways like YAP/TAZ, which inhibit the expression of adipogenic genes, are triggered when cortical act…

TSPO deficiency uncovers a novel role for porphyrins in adipocyte lipid metabolism.

The translocator protein (TSPO) is a mitochondrial outer membrane protein enriched in lipid-metabolic tissues, including white adipose tissue (WAT), but its physiological role in adipocytes remains poorly defined. Building on prior work that demonstrated a role for TSPO in mitochondrial fatty acid oxidation, we investigated whether TSPO contributes to adipocyte lipid homeostasis under metabolic stress. We employed a combination of in vivo and in vitro approaches using global Tspo knockout (Tspo-/-) mice, primary adipocyte cultures, and pharmacological TSPO-binding drugs to examine TSPO functio…

Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism.

Obesity increases circulating levels of the bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P). Here, we identify adipocyte-exp … and insulin sensitivity. Mechanistically, obesogenic diet promoted nuclear localization of SPHK2 in adipocytes, where it cooperated with transcription factors to suppress the thermogenic transcriptome. Adipocyte SPHK2 contributes to homeostatic circulating S1P levels and drive the pathogenic rise of S1P in response to obesogenic diet. Our findings reveal a d …

Reframing leukemia-niche interactions: the emerging role of the marrow adipocyte lineage.

The bone marrow is a highly dynamic organ that undergoes continuous remodeling to maintain all different hematopoietic cell populations thro … rella, obscuring the distinct contributions of specific stromal subsets; second, mature bone marrow adipocytes have traditionally been regarded as inert energy reservoirs rather than active components of the marrow microenvironment. Recent evidence challenges this view, demonstrating that different types of adipocyte lineage cells actively promote acute leuk …

Adipocyte-specific MC2R overexpression exerts minimal metabolic effects in mice.

BACKGROUND: Obesity is often associated with elevated glucocorticoid (GC) levels mediated by melanocortin 2 receptor (MC2R), the adrenocorticotropic hormone (ACTH) receptor expressed in the adrenal gland. Meanwhile, previous in vitro studies in non-adrenal cells suggest a potential role for MC2R in lipid metabolism in murine primary adipocytes; however, the functional relevance of MC2R in vivo remains poorly understood. Here, we assessed the metabolic effects and therapeutic potential of MC2R in obesity and GC regulation in vivo by generating mice with adipocyte-specific MC2R overexpression us…

Адипоцитный β-гидроксибутират обеспечивает метаболическую стойкость в множестве миеломы.

Множественная миелома (ММ) остается неизлечимым раком крови. Ожирение является известным фактором риска, но то, как адипоциты способствуют прогрессу MM, не в полной мере понятно. Здесь мы обнаруживаем метаболический перекресток между адипоцитами и клетками MM, который способствует выживанию клеток MM под глюкозой. Мы показываем, что ограничение глюкозы активирует АМПК, срывает связь HSP90-IRF4 и делает IRF4 восприимчивым к протеасомной деградации при помощи TRIM21. Парадоксально, но такой же стресс стимулирует адипоциты к производству β-гидроксибутирата (β-OHB). Клетки MM используют β-OHB при

Совпадение в аннотации оригинала
Multiple myeloma (MM) remains an incurable blood cancer. Obesity is a known risk factor, but how adipocytes promote MM progression is not fully understood. Here, we uncover a metabolic crosstalk between adipocytes and MM cells that promotes MM cell survival under glucose deprivation. We show that glucose restriction activates AMPK, disrupting HSP90-IRF4 bind…

Adipocyte-Tumor Interactions in the Bone Marrow Niche: Implications for Metastasis and Therapy.

Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidat…

GPx3 marks adipocyte lineage commitment in bone marrow stromal cells.

BACKGROUND: Bone marrow adipose tissue (BMAT) plays an essential role in skeletal health and systemic metabolism, particularly under conditi … ls in vitro. scRNA-seq analysis showed that GPx3 expression is predominantly localized in BMSCs and adipocytes, with reduced expression observed in aged mice, corresponding to elevated levels of adipocyte-related genes. In vitro functional experiments demonstrated that GPx3 knockdown significantly promoted adipogenic differentiation of BMSCs. CONCLUSION: Th …

The Lipid Enigma: A Case Report Highlighting Diagnostic Challenges in Adipocytic Tumors.

Infiltrating lipomas are a rare form of lipomas exhibiting unusual clinical behavior. We report a case of an adipocytic tumor of a 31-year-old male diagnosed with an infiltrating lipoma in the right submandibular region. It exhibits unusual clinical features such as invasion into surrounding structures, posing significant diagnostic challenges. The histopathological findings and differential diagnosis for this case are discussed, underscoring the importance of investigation techniques for accurate diagnosis and treatment planning. Infiltrating lipomas, while benign, can mimic malignant adipocy

Tumoral acidosis promotes adipose tissue depletion by fostering adipocyte lipolysis.

OBJECTIVE: Tumour progression drives profound alterations in host metabolism, such as adipose tissue depletion, an early event of cancer cachexia. As fatty acid consumption by cancer cells increases upon acidosis of the tumour microenvironment, we reasoned that fatty acids derived from distant adipose lipolysis may sustain tumour fatty acid craving, leading to the adipose tissue loss observed in cancer cachexia. METHODS: To evaluate the pro-lipolytic capacities of acid-exposed cancer cells, primary mouse adipocytes from subcutaneous and visceral adipose tissue were exposed to pH-matched condi…

AGPAT3 deficiency impairs adipocyte differentiation and leads to a lean phenotype in mice.

Acylglycerophosphate acyltransferases (AGPATs) catalyze the de novo formation of phosphatidic acid to synthesize glycerophospholipids and tr … e content. Mechanistically, Agpat3 was elevated during mouse and human adipogenesis and enriched in adipocytes. Agpat3-knockdown 3T3-L1 cells and Agpat3-deficient mouse embryonic fibroblasts (MEFs) have impaired adipogenesis in vitro. Interestingly, pioglitazone treatment rescued the adipogenic deficiency in Agpat3-deficient cells. We conclude that AGPAT3 re …

The Role of m6A in Osteoporosis and the Differentiation of Mesenchymal Stem Cells into Osteoblasts and Adipocytes.

Osteoporosis is a systemic disease in which bone mass decreases, leading to an increased risk of bone fragility and fracture. The occurrence of osteoporosis is believed to be related to the disruption of the differentiation of mesenchymal stem cells into osteoblasts and adipocytes. N6-adenylate methylation (m6A) modification is the most common type of chemical RNA modification and refers to a methylation modification formed by the nitrogen atom at position 6 of adenine (A), which is catalyzed by a methyltransferase. The main roles of m6A are the post-transcriptional level regulation of the sta…