Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation.

Abstract

Activation of peroxisome proliferator-activated receptor (PPAR) gamma, a nuclear receptor highly expressed in adipocytes, induces the differentiation of murine preadipocyte cell lines. Recently, thiazolidinediones (TZDs), a novel class of insulin-sensitizing compounds effective in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) have been shown to bind to PPARgamma with high affinity. We have examined the effects of these compounds on the differentiation of human preadipocytes derived from subcutaneous (SC) and omental (Om) fat. Assessed by lipid accumulation, glycerol 3-phosphate dehydrogenase activity, and mRNA levels, subcultured preadipocytes isolated from either SC or Om depots did not differentiate in defined serum-free medium. Addition of TZDs (BRL49653 or troglitazone) or 15-deoxyDelta12,14prostaglandin J2 (a natural PPARgamma ligand) enhanced markedly the differentiation of preadipocytes from SC sites, assessed by all three criteria. The rank order of potency of these agents in inducing differentiation matched their ability to activate transcription via human PPARgamma. In contrast, preadipocytes from Om sites in the same individuals were refractory to TZDs, although PPARgamma was expressed at similar levels in both depots. The mechanism of this depot-specific TZD response is unknown. However, given the association between Om adiposity and NIDDM, the site-specific responsiveness of human preadipocytes to TZDs may be involved in the beneficial effects of these compounds on in vivo insulin sensitivity.

Macrophage-conditioned medium inhibits the differentiation of 3T3-L1 and human abdominal preadipocytes

“…Similar to other adipogenic protocols containing PPARγ agonists (e.g. indomethacin-see Methods), we observed that subcutaneous preadipocytes differentiated somewhat better than their omental counterparts [20,26].…”

“…To minimise inter-subject variability, the subcutaneous and omental adipose tissue for these studies were paired samples. The maximal differentiation response of the omental preadipocytes was somewhat lower than that of subcutaneous preadipocytes as observed by others [20,26]. Interestingly, omental/visceral adipose tissue contains more macrophages than does subcutaneous fat in obese rodents and humans [11].…”

“…The digested tissue underwent progres-sive size filtration and centrifugation (200×g) to remove mature adipocytes, followed by incubation in erythrocyte lysis buffer, to yield the stromal cells. These were seeded and grown in DMEM supplemented with 20% FBS and antibiotics, and then expanded by further cell passages (maximum of three) before being subjected to differentiation [20,21]. In some cases, the cells underwent cryopreservation (once, prior to passaging) without altering their ability to differentiate upon thawing [22].…”

Hypertrophy and hyperplasia of abdominal adipose tissues in women

“…[28][29][30] Recent studies using microarray analysis have also shown that fat tissue or preadipocytes from omental and subcutaneous fat depots have distinct expression profiles. 30,31 Differences in the expression of adipogenic genes in fat cells from different depots could contribute to regional fat distribution.…”

Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease

“…[12][13][14] Peroxisome proliferator-activated receptor g (PPARg) mediates the transcriptional enhancement of a number of genes encoding proteins that regulate lipid metabolism, suggesting a pivotal role in the adipogenic signaling cascade and lipid homeostasis. 15 Rosiglitazone (RSG), a PPARg agonist and an approved antidiabetic pharmacotherapy, is an insulinsensitizing agent that allows the body to use endogenous insulin more efficiently, maintain normal physiological feedback mechanisms 16,17 and produce anti-inflammatory actions. 18 A positive cognitive effect has been observed in a small pilot study of RSG in AD patients.…”