Subclass distribution of low-density lipoprotein triglyceride and the clustering of metabolic syndrome components in Japanese children.

BACKGROUND: Recent studies demonstrated that low-density lipoprotein-tryglyceride (LDL-TG) may represent another marker of cardiovascular risks. We therefore measured LDL-TG including the low-density lipoprotein (LDL) subclass distribution and investigated the association between LDL-TG subclass profile and the clustering of metabolic syndrome (MetS) components and insulin resistance in Japanese children. METHODS: The study included 237 schoolchildren (boys 115, girls 122). Four subclasses of low-density lipoprotein-tryglyceride (large, medium, small, and very small) was quantified using high-performance liquid chromatography. Total LDL-TG and TG levels in LDL subclasses were evaluated among four MetS component groups; non-abdominal obesity, abdominal obesity, pre-MetS, and MetS. RESULTS: Total LDL-TG (P = 0.0003, P = 0.0175) and triglyceride levels in LDL subclasses were significantly different among four MetS component groups (large: P = 0.0002, P = 0.0084; medium: P = 0.0009, P = 0.0491; small: P =0.0025, P = 0.0509; very small: P = 0.0808, P = 0.0228; boys and girls, respectively). Total LDL-TG (r = 0.411, P < 0.0001, r = 0.378. P < 0.0001) and triglyceride levels in LDL subclasses correlated positively with the homeostasis model of assessment ratio (large: r = 0.396, P < 0.0001, r = 0.346, P < 0.0001; medium: r = 0.274, P = 0.0030, r = 0.228, P = 0.0115; small: r = 0.342, P = 0.0002, r = 0.292, P = 0.0011; very small: r = 0.385, P < 0.0001, r = 0.426, P < 0.0001, boys and girls, respectively). CONCLUSIONS: Subclass distribution of LDL-TG was significantly associated with the clustering of MetS components in both sexes, and insulin resistance is a significant determinant of LDL-TG in all LDL subclasses. Lipoprotein-tryglyceride subclass analysis, rather than LDL-C, may provide a precise evaluation for cardiovascular disease risks in children with MetS.

An Efficient Method to Obtain Dedifferentiated Fat Cells.

Tissue engineering and cell therapy hold great promise clinically. In this regard, multipotent cells, such as mesenchymal stem cells (MSCs), may be used therapeutically, in the near future, to restore function to damaged organs. Nevertheless, several technical issues, including the highly invasive procedure of isolating MSCs and the inefficiency surrounding their amplification, currently hamper the potential clinical use of these therapeutic modalities. Herein, we introduce a highly efficient method for the generation of dedifferentiated fat cells (DFAT), MSC-like cells. Interestingly, DFAT cells can be differentiated into several cell types including adipogenic, osteogenic, and chondrogenic cells. Although other groups have previously presented various methods for generating DFAT cells from mature adipose tissue, our method allows us to produce DFAT cells more efficiently. In this regard, we demonstrate that DFAT culture medium (DCM), supplemented with 20% FBS, is more effective in generating DFAT cells than DMEM, supplemented with 20% FBS. Additionally, the DFAT cells produced by our cell culture method can be redifferentiated into several tissue types. As such, a very interesting and useful model for the study of tissue dedifferentiation is presented.

Non-high-density Lipoprotein Cholesterol Levels in Japanese Obese Boys with Metabolic Syndrome.

AIM: To investigate the relationship between the clustering of metabolic syndrome (MetS) components and non-high-density lipoprotein cholesterol (non-HDL-C) levels in Japanese obese boys. METHODS: Subjects were 58 obese boys aged 12.0±2.6 years, which were categorized into three subgroups: abdominal obesity, pre-MetS (abdominal obesity＋1 component), and MetS (abdominal obesity＋2 or more components). RESULTS: Sixteen (27.6%) and 32 (55.2%) of the obese boys were diagnosed as pre-MetS and MetS, respectively. The mean non-HDL-C level in total subjects was 139.0±36.4 mg/dl and that in boys with abdominal obesity, pre-MetS, and MetS were 112.9±34.4, 135.4±37.9, and 149.0±32.6 mg/dl, respectively (p=0.0183, ANOVA). CONCLUSIONS: Japanese obese boys with MetS exhibited elevated non-HDL-C levels, suggesting that they may have a higher risk for the development of atherosclerotic diseases.

Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6.

INTRODUCTION: Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs. METHODS: We examined the effects of 10(6) of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 10(6) of DFAT cells transfected with TSG-6 siRNA through tail vein. RESULTS: Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12ß mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats. CONCLUSION: Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of IL-6, IL-10 and IL-12ß, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment of immunological progressive renal diseases.

Effect of cod liver oil supplementation on the stearoyl-CoA desaturase index in obese children: a pilot study.

To investigate the effects of n-3 polyunsaturated fatty acids on stearoyl-CoA desaturase (SCD) activity, we treated 10 obese children (mean age: 12.9 years) with cod liver oil once daily for 12 weeks. The effects of cod liver oil supplementation on SCD activity, as estimated by the palmitoleate/palmitate ratio, depended on the docosahexaenoic acid (DHA) contents at baseline. Baseline DHA contents were negatively correlated with baseline SCD activity. After the treatment, baseline DHA contents were found to be significantly associated with the reduction of SCD activity. Cod liver oil supplementation may be a complementary treatment for obese children with low baseline contents of DHA.

Osteogenic effects of dedifferentiated fat cell transplantation in rabbit models of bone defect and ovariectomy-induced osteoporosis.

We have previously reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and the potential to differentiate into lineages of mesenchymal tissue similar to bone marrow mesenchymal stem cells (MSCs). In the present study, we examined the effects of autologous DFAT cell transplantation on bone regeneration in a rabbit bone defect model and an ovariectomy (OVX)-induced osteoporosis model. The formation of tissue-engineered bone (TEB) was observed when rabbit DFAT cells were loaded onto a ß-tricalcium phosphate (TCP)/collagen sponge and cultured in an osteogenic differentiation medium for 3 weeks. Autologous implantation of DFAT cell-mediated TEB constructs promoted bone regeneration in a rabbit tibial defect model. Regenerated bone tissue induced by transplantation of DFAT cell-mediated TEB constructs was histologically well differentiated and exhibited higher bone strength in a three-point bending test compared to that induced by the ß-TCP/collagen sponge alone. In OVX-induced osteoporosis model rabbits, DFAT cells were obtained with the osteogenic activity similar to cells from healthy rabbits. Intrabone marrow injection of autologous DFAT cells significantly increased the bone mineral density (BMD) at the injected site in the OVX rabbits. Transplanted DFAT cells remained mainly on the injection side of the bone marrow by at least 28 days after intrabone marrow injection and a part of them expressed osteocalcin. In conclusion, these results demonstrate that autologous implantation of DFAT cells contributed to bone regeneration in a rabbit bone defect model and an OVX-induced osteoporosis model. DFAT cells may be an attractive cell source for cell-based bone tissue engineering to treat nonunion fractures in all patients, including those with osteoporosis.