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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS2-12, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59% increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50%. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-gamma2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages.
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PMID:Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. 1009 97

Bone density, anthropometric data, and markers of bone turnover were collected on 21 subjects diagnosed with Prader-Willi syndrome (PWS) and compared with 9 subjects with obesity of unknown cause. In addition, urinary N-telopeptide levels were obtained in all subjects. N-telopeptides are the peptide fragments of type I collagen, the major bone matrix material. During periods of active bone degradation or high bone turnover, high levels of N-telopeptides are excreted in the urine. However, no significant difference was detected in the urinary N-telopeptide levels when corrected for creatinine excretion (raw or transformed data) between our subjects with obesity or PWS and the observed effect size of the between-group difference was small. Although N-telopeptide levels were higher but not significantly different in the subjects with PWS compared with obese controls, the subjects with PWS had significantly decreased total bone and spine mineral density and total bone mineral content (all P < 0.001). No differences in N-telopeptide levels or bone mineral density were observed between subjects with PWS and chromosome 15q deletion or maternal disomy. Thus, decreased bone mineral density in subjects with PWS may relate to the lack of depositing bone mineral during growth when bones are becoming more dense (e.g., during adolescence), possibly because of decreased production of sex or growth hormones and/or long-standing hypotonia. It may not be caused by loss, or active degradation, of bone matrix measurable by the methods described in this study further supporting the possible need for hormone therapy during adolescence.
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PMID:Decreased bone mineral density in Prader-Willi syndrome: comparison with obese subjects. 1174 93

Clinical trials of isoflavone supplementation and bone density have been of relatively short duration and yielded inconsistent results. Few studies examined the effects of usual dietary isoflavone intake on bone density, and none examined the effects on markers of bone turnover. This cross-sectional study examines the association of usual, unsupplemented dietary soy intake with bone density at the lumbar spine and hip and markers of bone turnover in postmenopausal women. Participants were 208 postmenopausal Southern California women aged 45-74 years. Information on behavioral and lifestyle factors was obtained, and dietary intake of isoflavones over the past year was assessed with a standardized questionnaire. Bone density was measured at the spine and hip with dual energy x-ray absorptiometry (DEXA). Urinary type I collagen cross-linked N-telopeptides (N-Tx) and pyridinium cross-links (PYR), both markers of bone resorption, and bone alkaline phosphatase (BAP), a marker of bone formation, were assayed. After adjustment for age and obesity, women with the highest daily intake of dietary genistein had N-Tx concentrations 18% lower than those of women who reported no daily genistein consumption (mean 37.29 vs. 45.44, respectively, p = 0.01). After adjustment for all covariates, there were trends toward significant differences in N-Tx (p = 0.09) and spine bone density (p = 0.07), whereby women with the highest level of isoflavone consumption had greater bone density at the spine. These results suggest that usual, unsupplemented dietary isoflavone consumption may be protective against bone loss in postmenopausal women through a reduction in bone resorption.
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PMID:Usual dietary isoflavone intake, bone mineral density, and bone metabolism in postmenopausal women. 1186 Jul 27

Bone turnover in neonates appears independently of the comparably low maternal bone turnover, but there is only sparse information on the effect of the in utero environment on fetal bone turnover. Postnatally, the resuming growth velocity and alterations in mineral homeostasis affect neonatal bone turnover. This study evaluated the relationship of bone marker concentrations to maternal and fetal auxological variables as well as maternal smoking and assessed the short-term change in bone markers during the first days of life. Serum markers of bone formation [osteocalcin and bone-specific alkaline phosphatase (BALP)] and bone resorption (C-terminal telopeptide of type I collagen) were measured in cord blood and at discharge (median d 3) in 69 healthy term neonates. Concentrations of BALP were significantly lower in neonates of smokers (n = 16) compared with nonsmokers (n = 53), both at birth (p = 0.013) and at discharge (p = 0.036). Both cord osteocalcin and BALP were negatively related to maternal weight and maternal body mass index. Maternal smoking and pregnancy weight gain were the predictors of cord BALP (r2 = 0.24; p < 0.001), whereas the mode of delivery best predicted cord C-terminal telopeptide of type I collagen levels (r2 = 0.19; p < 0.001). C-terminal telopeptide of type I collagen and osteocalcin increased significantly (p < 0.001) from birth to discharge, whereas BALP levels did not change significantly during the same period. Our results suggest that maternal smoking during pregnancy and maternal obesity may have a negative impact on fetal bone formation. The significant increase of osteocalcin and C-terminal telopeptide of type I collagen may result either from an increase in bone turnover or altered renal clearance.
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PMID:Perinatal bone turnover in term human neonates and the influence of maternal smoking. 1262 Nov 14

Childhood obesity is prevalent and linked to the development of Type 2 diabetes mellitus (DM) and poor bone health. Some PUFA enhance bone mass and thus may improve bone health in obese children. The study objective was to determine the effects of dietary (n-6) compared with (n-3) essential PUFA and long-chain PUFA (LCPUFA) on bone in an obese and insulin-resistant state. Male fa/fa (n = 48) and lean Zucker rats (n = 48) were fed diets containing safflower oil [SO, high (n-6) PUFA], flaxseed oil [FXO, high (n-3) PUFA], or menhaden oil [MO, high (n-3) LCPUFA] for 9 wk. Measurements included the following: femur bone area (BA), mineral content (BMC), density (BMD), morphometry and ex vivo release of prostaglandin E(2) (PGE(2)); plasma osteocalcin and C-terminal telopeptides of type I collagen. Differences among groups were detected using 2-way ANOVA. Genotype effects in the fa/fa rats included lower femoral weight, length, BA, and BMC, as well as femoral head and proximal epiphysis widths compared with the lean rats, but BMD was not affected. Femur BA, BMC, and BMD did not differ among the dietary groups, but diaphysis width was elevated in the MO group and PGE(2) release was reduced by the FXO and MO diets. No genotype x diet interactions were observed. These data indicate that the fa/fa Zucker rat is at risk for low bone mass and that dietary (n-3) FA effectively reduce PGE(2) release. Whether reduced PGE(2) will support optimal peak bone mass during childhood and conserve bone mass with aging warrants investigation.
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PMID:(n-3) fatty acids reduce the release of prostaglandin E2 from bone but do not affect bone mass in obese (fa/fa) and lean Zucker rats. 1573 84

White adipose tissue (WAT) mass is the main determinant of obesity and associated health risks. WAT expansion results from increases in white adipocyte cell number and size, which in turn reflect a series of shifts in the cellular metabolic state. To quantitatively profile the metabolic alterations occurring during de novo adipocyte formation, metabolic flux analysis (MFA) was used in conjunction with a novel modularity analysis algorithm on differentiating 3T3-L1 preadipocytes. Use of a type I collagen gel as an effective long-term culture substrate was also assessed. The calculated flux distributions predicted the sequential activation of several intracellular cross-compartmental pathways, including lipogenesis, the pentose phosphate pathway, and the malate cycle, in good agreement with earlier isotopic tracer experiments and gene profiling studies. Partition of the adipocyte metabolic network into highly interacting reaction subgroups suggested a functional reorganization of the major pathways consistent with the lipid-loading phenotype of the adipocyte. Flux and modularity analysis results together point to the flux distribution around pyruvate as a key indicator of adipocyte lipid accumulation.
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PMID:Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation. 1728 73

Several lines of epidemiological evidence have suggested that non-alcoholic steatohepatitis (NASH) is closely associated with obesity in humans. However, the precise mechanisms of the progression of NASH and its key metabolic abnormalities remain to be elucidated. We found that long-term high-fat diet (HFD) exposure induces NASH, with excess body weight, hyperinsulinemia and hypercholesteremia in mice. Longitudinal analysis of the model showed that steatohepatitis was induced after onset of metabolic abnormalities. In addition, we found that expression of MCP-1 mRNA was induced in the liver before induction of TNFalpha and type I collagen alpha1 mRNAs, and prior to onset of steatohepatitis. We confirmed that hepatic MCP-1 contents were increased in mice fed HFD for 50 weeks, although the precise role of MCP-1 in the development of NASH remains to be addressed. The mouse model was also characterized by moderate reductions in catalase activity and glutathione content, as well as by overexpression of fatty acid synthase, acetyl-CoA carboxylase 1 and FAT/CD36 mRNAs in the liver. The murine NASH model apparently mimics clinical aspects of the condition and provides insight into NASH.
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PMID:Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet. 1730 Jun 98

Visfatin (also known as pre-B cell colony-enhancing factor or PBEF) is a novel adipocytokine that is highly expressed in visceral fat and upregulated in obesity and type 2 diabetes mellitus. Visfatin binds to and activates the insulin receptor (IR), thereby exerting insulin-mimetic effects in various cell lines. IR has been detected in osteoblasts, which is consistent with the role of insulin as an important osteotropic hormone. This study investigated the actions of visfatin on human primary osteoblasts. The expression and tyrosine phosphorylation of IR, IR substrate-1 (IRS-1), and IRS-2 were determined by immunoprecipitation and immunoblotting. Cell proliferation was determined by measuring [(3)H]thymidine incorporation and cell number. Glucose uptake was determined by measuring 2-[(3)H]deoxyglucose incorporation. Real-time quantitative reverse-transcription polymerase chain reaction (PCR) was used for determining alkaline phosphatase (ALP), osteocalcin, and type I collagen mRNA expression. Enzyme-linked immunosorbent assay and radioimmunoassay were used for measuring ALP activity, osteocalcin secretion, and type I collagen production. We found that visfatin induced tyrosine phosphorylation of IR, IRS-1, and IRS-2. Moreover, the effects of visfatin - glucose uptake, proliferation, and type I collagen enhancement of cultured human osteoblast-like cells - bore a close resemblance to those of insulin and were inhibited by hydroxy-2-naphthalenylmethylphosphonic acid tris-acetoxymethyl ester, a specific inhibitor of IR tyrosine kinase activity. We also unexpectedly found that visfatin downregulated osteocalcin secretion from human osteoblast-like cells. These data indicate that the regulation of glucose uptake, proliferation, and type I collagen production by visfatin in human osteoblasts involves IR phosphorylation, the same signal-transduction pathway used by insulin.
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PMID:Insulin-like effects of visfatin on human osteoblasts. 1734 Feb 25

We previously found that cathepsin K (CTSK) played an important role in adipocyte differentiation. However, the underlying molecular mechanism is not clear. Through the time window study, it was observed that CTSK activities were required mainly in the early phases of adipogenic process. At the same time, the expression of type I collagen disappeared. However, type I collagen can still be observed during the whole process when the CTSK inhibitor-E64 was added. The mRNA levels of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and CCAAT/enhancer binding protein alpha (C/EBP-alpha) was also declining. These imply that CTSK may play a role in adipogenesis in early differentiation phases and produce an effect at least partly by degrading type I collagen, which may provides a basis for developing novel therapeutic approaches to treat obesity and the diseases associated with it.
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PMID:Cathepsin K regulates adipocyte differentiation: possible involvement of type I collagen degradation. 1884 Sep 28

Obesity is considered a chronic low-grade inflammatory status and the stromal vascular fraction (SVF) cells of adipose tissue (AT) are considered a source of inflammation-related molecules. We identified YKL-40 as a major protein secreted from SVF cells in human visceral AT. YKL-40 expression levels in SVF cells from visceral AT were higher than in those from subcutaneous AT. Immunofluorescence staining revealed that YKL-40 was exclusively expressed in macrophages among SVF cells. YKL-40 purified from SVF cells inhibited the degradation of type I collagen, a major extracellular matrix of AT, by matrix metalloproteinase (MMP)-1 and increased rate of fibril formation of type I collagen. The expression of MMP-1 in preadipocytes and macrophages was enhanced by interaction between these cells. These results suggest that macrophage/preadipocyte interaction enhances degradation of type I collagen in AT, meanwhile, YKL-40 secreted from macrophages infiltrating into AT inhibits the type I collagen degradation.
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PMID:YKL-40 secreted from adipose tissue inhibits degradation of type I collagen. 1966 3


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