Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation

Vyver, Marí van de; Andrag, Ellen; Cockburn, I L; Ferris, William F.

doi:10.1530/joe-14-0425

Cited by 13 publications

(9 citation statements)

References 54 publications

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“…The resulting metabolic improvement is also contributed to by increased adiponectin secretion; the net result being improved insulin sensitivity and prevention/improvement of type 2 diabetes ( 106 ). Of course the weight gain has negative musculoskeletal and cosmetic implications and the enhanced adipocyte differentiation may be at the expense of reduced osteoblast differentiation in bone with consequent reduction of bone density ( 107 ).…”

Section: Implications For Pathophysiology/therapymentioning

confidence: 99%

Control of Adipocyte Differentiation in Different Fat Depots; Implications for Pathophysiology or Therapy

et al. 2015

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Adipocyte differentiation and its impact on restriction or expansion of particular adipose tissue depots have physiological and pathophysiological significance in view of the different functions of these depots. Brown or “beige” fat [brown adipose tissue (BAT)] expansion can enhance thermogenesis, lipid oxidation, insulin sensitivity, and glucose tolerance; conversely expanded visceral fat [visceral white adipose tissue (VAT)] is associated with insulin resistance, low grade inflammation, dyslipidemia, and cardiometabolic risk. The largest depot, subcutaneous white fat [subcutaneous white adipose tissue (SAT)], has important beneficial characteristics including storage of lipid “out of harms way” and secretion of adipokines, especially leptin and adiponectin, with positive metabolic effects including lipid oxidation, energy utilization, enhanced insulin action, and an anti-inflammatory role. The absence of these functions in lipodystrophies leads to major metabolic disturbances. An ability to expand white adipose tissue adipocyte differentiation would seem an important defense mechanism against the detrimental effects of energy excess and limit harmful accumulation of lipid in “ectopic” sites, such as liver and muscle. Adipocyte differentiation involves a transcriptional cascade with PPARγ being most important in SAT but less so in VAT, with increased angiogenesis also critical. The transcription factor, Islet1, is fairly specific to VAT and in vitro inhibits adipocyte differentiation. The physiological importance of Islet1 requires further study. Basic control of differentiation is similar in BAT but important differences include the effect of PGC-1α on mitochondrial biosynthesis and upregulation of UCP1; also PRDM16 plays a pivotal role in expression of the BAT phenotype. Modulation of the capacity or function of these different adipose tissue depots, by altering adipocyte differentiation or other means, holds promise for interventions that can be helpful in human disease, particularly cardiometabolic disorders associated with the world wide explosion of obesity.

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Section: Implications For Pathophysiology/therapymentioning

confidence: 99%

Control of Adipocyte Differentiation in Different Fat Depots; Implications for Pathophysiology or Therapy

et al. 2015

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“…To determine whether any of these cells correspond to adipocyte progenitors, we exposed cultures to adipogenic conditions. Because activation of PPARγ (peroxisome-proliferator activated receptor gamma) by ligands such as thiazolidenediones can induce lipid accumulation in cells independently of adipogenic conversion 16 , we used a minimal adipogenic cocktail of 3-isobutyl-1-methylxanthine, dexamethasone and insulin (MDI). After approximately 6 days, we observed a loss of continuity between cells forming the capillary structure, and lipid droplets in cells within the capillaries ( Fig.…”

mentioning

confidence: 99%

Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice

Min

Kady

Nam

et al. 2016

Nat Med

278

226

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The uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots1–4, in adipocytes termed ‘brite’ (brown-in-white) or ‘beige’. In humans, the presence of ‘brite/beige’ adipocytes correlates with a lean, metabolically healthy phenotype5–8, but whether a causal relationship exists is not clear. Here we report that human ‘brite/beige’ adipocyte progenitors proliferate in response to pro-angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform from being UCP1-negative to UCP1-positive in response to adenylate cyclase activation, a defining feature of the ‘beige/brite’ phenotype, and display uncoupled respiration. When implanted into normal or high fat diet-fed, glucose intolerant NOD-scid IL2rgnull mice, activated ‘brite/beige’ adipocytes enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Thus, pro-angiogenic conditions drive proliferation of human ‘beige/brite’ adipocyte progenitors, and activated ‘beige/brite’ adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism.

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“…Unlike most publications that used adipogenic cocktails containing multiple ingredients for the adipocyte differentiation from a range of progenitors in vitro, we found that rosiglitazone and insulin are necessary and sufficient for the adipogenic induction of CD34+CD31+ cells. While we are aware that rosiglitazone alone can induce a lipid accumulation in non-adipose cells 35 , the molecular signature for pan-adipocyte and brown/beige adipocyte markers, including a UCP-1 protein expression in select cells, confirms the mature adipocyte phenotype of some of the differentiated cells. Our two-ingredient adipogenic cocktail simplifies the procedural protocol and makes it more cost-effective.…”

mentioning

confidence: 77%

Isolation, Expansion, and Adipogenic Induction of CD34+CD31+ Endothelial Cells from Human Omental and Subcutaneous Adipose Tissue

Haynes

Huyck

James

et al. 2018

JoVE

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Obesity is accompanied by an extensive remodeling of adipose tissue primarily via adipocyte hypertrophy. Extreme adipocyte growth results in a poor response to insulin, local hypoxia, and inflammation. By stimulating the differentiation of functional white adipocytes from progenitors, radical hypertrophy of the adipocyte population can be prevented and, consequently, the metabolic health of adipose tissue can be improved along with a reduction of inflammation. Also, by stimulating a differentiation of beige/brown adipocytes, the total body energy expenditure can be increased, resulting in weight loss. This approach could prevent the development of obesity co-morbidities such as type 2 diabetes and cardiovascular disease. This paper describes the isolation, expansion, and differentiation of white and beige adipocytes from a subset of human adipose tissue endothelial cells that co-express the CD31 and CD34 markers. The method is relatively cheap and is not labor-intensive. It requires access to human adipose tissue and the subcutaneous depot is suitable for sampling. For this protocol, fresh adipose tissue samples from morbidly obese subjects [body mass index (BMI) >35] are collected during bariatric surgery procedures. Using a sequential immunoseparation from the stromal vascular fraction, enough cells are produced from as little as 2-3 g of fat. These cells can be expanded in culture over 10-14 days, can be cryopreserved, and retain their adipogenic properties with passaging up to passage 5-6. The cells are treated for 14 days with an adipogenic cocktail using a combination of human insulin and the PPARγ agonist-rosiglitazone. This methodology can be used for obtaining proof of concept experiments on molecular mechanisms that drive adipogenic responses in adipose endothelial cells, or for screening new drugs that can enhance the adipogenic response directed either towards white or beige/brown adipocyte differentiation. Using small subcutaneous biopsies, this methodology can be used to screen out non-responder subjects for clinical trials aimed to stimulate beige/brown and white adipocytes for the treatment of obesity and co-morbidities.

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Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation

Cited by 13 publications

References 54 publications

Control of Adipocyte Differentiation in Different Fat Depots; Implications for Pathophysiology or Therapy

Control of Adipocyte Differentiation in Different Fat Depots; Implications for Pathophysiology or Therapy

Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice

Isolation, Expansion, and Adipogenic Induction of CD34+CD31+ Endothelial Cells from Human Omental and Subcutaneous Adipose Tissue

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