Subcutaneous adipose tissue expansion mechanisms are similar in early and late onset overweight/obesity.

Background/objective: The development of overweight/obesity associates with alterations in white adipose tissue (WAT) cellularity (fat cell size/number) and lipid metabolism, in particular lipolysis. If these changes differ between early/juvenile (EOO < 18 years of age) or late onset overweight/obesity (LOO) is unknown and was presently examined.

Subjects/methods: We included 439 subjects with validated information on body mass index (BMI) at 18 years of age.

Application of Gene Expression Trajectories Initiated from ErbB Receptor Activation Highlights the Dynamics of Divergent Promoter Usage.

Understanding how cells use complex transcriptional programs to alter their fate in response to specific stimuli is an important question in biology. For the MCF-7 human breast cancer cell line, we applied gene expression trajectory models to identify the genes involved in driving cell fate transitions. We modified trajectory models to account for the scenario where cells were exposed to different stimuli, in this case epidermal growth factor and heregulin, to arrive at different cell fates, i.

Promoter-level expression clustering identifies time development of transcriptional regulatory cascades initiated by ErbB receptors in breast cancer cells.

The analysis of CAGE (Cap Analysis of Gene Expression) time-course has been proposed by the FANTOM5 Consortium to extend the understanding of the sequence of events facilitating cell state transition at the level of promoter regulation. To identify the most prominent transcriptional regulations induced by growth factors in human breast cancer, we apply here the Complexity Invariant Dynamic Time Warping motif EnRichment (CIDER) analysis approach to the CAGE time-course datasets of MCF-7 cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). We identify a multi-level cascade of regulations rooted by the Serum Response Factor (SRF) transcription factor, connecting the MAPK-mediated transduction of the HRG stimulus to the negative regulation of the MAPK pathway by the members of the DUSP family phosphatases.

Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density.

Unlabelled: One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmenopausal women with low BMD.

Increased activity of hepatic microsomal triglyceride transfer protein and bile acid synthesis in gallstone disease.

Unlabelled: A strong interrelationship exists between the regulation of bile acid (BA) metabolism and hepatic very low density lipoprotein (VLDL) production. We have recently shown that BA synthesis is increased in gallstone disease. We investigated the activity of hepatic microsomal triglyceride transfer protein (MTTP) as a surrogate of VLDL production, BA synthesis, and mRNA expression levels of proteins that regulate fatty acid (FA) metabolism in the liver of gallstone (GS) patients compared with GS-free patients.

Bile acid synthesis in humans has a rapid diurnal variation that is asynchronous with cholesterol synthesis.

Background & Aims: The conversion of cholesterol to bile acids by the liver is an important regulator of body cholesterol homeostasis. In rodents, both cholesterol and bile acid synthesis have marked diurnal rhythms that peak synchronously at midnight. The aim of this study was to establish whether such diurnal rhythms are also present in healthy humans.

Pituitary control of cholesterol metabolism in normal and LDL receptor knock-out mice: effects of hypophysectomy and growth hormone treatment.

The pituitary is important in the control of lipid metabolism and studies of hypophysectomized (Hx) rats have shown strong effects of growth hormone (GH) on bile acid synthesis, hepatic LDL receptor (LDLR) expression and on the sensitivity to dietary cholesterol. It is unclear if mice may be used in such studies. The aim of the current study was to evaluate if Hx mice may be used to further explore how GH modulates cholesterol and bile acid metabolism, and to define the importance of the LDLR in this regulation by studying LDLR-deficient mice (LDLRko).

Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice.

Thyroid hormones [predominantly 3,5,3'-triiodo-L-thyronine (T3)] regulate cholesterol and lipoprotein metabolism, but cardiac effects restrict their use as hypolipidemic drugs. T3 binds to thyroid hormone receptors (TRs) alpha and beta. TRbeta is the predominant isoform in liver, whereas T3 effects on heart rate are mediated mostly by TRalpha.

Control of ACAT2 liver expression by HNF1.

ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes.

The effect of physical training on bone mineral density in women with endometriosis treated with GnRH analogs: a pilot study.

Background: The effect of physical training on bone mineral density (BMD) in women with endometriosis treated with gonadotropin-releasing hormone (GnRH) analogs was studied.

Methods: Nineteen Caucasian premenopausal women aged 23-38 years were included in the study. The subjects were all treated with 21.

Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations.

Objective: Cardiovascular disease with premature atherosclerosis is common in patients with systemic lupus erythematosus (SLE). We previously identified elevated levels of oxidized low-density lipoprotein (OxLDL) together with elevated levels of autoantibodies related to OxLDL as risk factors for cardiovascular disease in female patients with SLE. Autoantibodies to OxLDL are common in SLE and cross-react with anticardiolipin antibodies (aCL).

Physical training and hormone replacement therapy reduce the decrease in bone mineral density in perimenopausal women: a pilot study.

The effects of physical training and hormone replacement therapy (HRT) on bone mineral density in perimenopausal women were studied. Sixty perimenopausal women were randomized to either physical training (n = 20), HRT (n = 20), or control group (n = 20). The study period was 18 months.

ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver.

Background: Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes, ACAT1 and ACAT2, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification.

Methods And Results: In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein was found in Kupffer cells only.

Changes in bone mineral density differ between gonadotrophin-releasing hormone analogue- and surgically castrated men with prostate cancer--a prospective, controlled, parallel-group study.

Objective: The effects of surgical and medical castration on bone mineral density (BMD) were compared in men receiving castration therapy as a result of prostate cancer. A control group of men of similar age was also included in the study.

Material And Methods: A total of 28 men with prostatic cancer who had been selected to undergo medical or surgical castration and 10 healthy men with benign urological disorders were followed from baseline observations and BMD was assessed at 3, 6, 12 and 36 months.

Growth hormone induces low-density lipoprotein clearance but not bile acid synthesis in humans.

Objective: Growth hormone (GH) induces hepatic low-density lipoprotein (LDL) receptors and lowers plasma cholesterol. We characterized the influence of GH treatment on plasma LDL clearance in normal humans and investigated the relative role of LDL receptor (LDLR) activity and stimulation of bile acid synthesis in subjects with different LDLR expression.

Methods And Results: Plasma clearance of autologous 125I-LDL was measured before and during 3 weeks of treatment with GH (0.

Leptin induces the hepatic high density lipoprotein receptor scavenger receptor B type I (SR-BI) but not cholesterol 7alpha-hydroxylase (Cyp7a1) in leptin-deficient (ob/ob) mice.

Cholesterol elimination from the body involves reverse cholesterol transport from peripheral tissues in which the elimination of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol by the liver and subsequent biliary excretion as free cholesterol and bile acids are important. In situations of peripheral fat and cholesterol accumulation, such as obesity, these pathways may be overloaded, contributing to increased cholesterol deposition. Leptin has an important role in obesity, suppressing food intake and increasing energy expenditure.

Incidence and survival of Swedish patients with differentiated thyroid cancer.

Papillary (PTC) and follicular (FTC) thyroid cancers are rare disorders but are, nevertheless, among the most common cancers in individuals below 40 years of age. From the population-based Swedish Cancer Registry we identified 3,588 individuals with PTC and 1,966 with FTC during 1958-87. Histopathology was determined by examining the original histopathology reports.

Reverse cholesterol transport in man: promotion of fecal steroid excretion by infusion of reconstituted HDL.

Reverse cholesterol transport is a complex process, which transfers cholesterol from peripheral cells to the liver for subsequent elimination as bile acids and neutral steroids. Although apo A-I in high density lipoproteins (HDL) is believed to have a crucial role in this process, clinical conditions with very low HDL cholesterol levels appear to maintain normal cholesterol excretion. On the other hand, infusion of 'artificial HDL' in the form of recombinant proapo A-I (4 g) liposome complexes results in increased fecal steroid excretion, corresponding to a removal of approximately 0.

Monitoring hepatic cholesterol 7alpha-hydroxylase activity by assay of the stable bile acid intermediate 7alpha-hydroxy-4-cholesten-3-one in peripheral blood.

We describe an accurate method for monitoring the enzymatic activity of hepatic cholesterol 7alpha-hydroxylase (C7alphaOH; CYP7A1), the rate-limiting and major regulatory enzyme in the synthesis of bile acids. Assay of 7alpha-hydroxy-4-cholesten-3-one (C4), an intermediate in bile acid synthesis, revealed that the level of C4 in peripheral blood serum or plasma showed a strong correlation to the enzymatic activity of hepatic C7alphaOH, both at steady-state conditions (r = 0.929) as well as during the rapid changes that occur during the diurnal phases.

Pharmacological interference with intestinal bile acid transport reduces plasma cholesterol in LDL receptor/apoE deficiency.

Reduction of plasma cholesterol by statins is fundamental to prevent coronary heart disease. Such therapy is often sub-optimal, however, particularly in patients with reduced LDL receptors (familial hypercholesterolemia), and novel or adjuvant therapies are therefore warranted. Cholesterol elimination is profoundly influenced by the rate of its conversion to bile acids (BA), regulated by the enzyme Cyp7a1.

Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes.

Site differences in adipose tissue function may have implications for insulin-resistant conditions. In mature adipose tissue, subcutaneous adipocytes have higher leptin secretion, similar tumor necrosis factor (TNF)-alpha secretion, and lower catecholamine-stimulated lipolysis as compared with omental adipocytes. In this study, lipolysis and leptin and TNF-alpha secretion were compared between human omental and subcutaneous preadipocytes.

Structural skeletal impairment induced by immunosuppressive therapy in rats: cyclosporine A vs tacrolimus.

The exact role of immunosuppressive drugs in the development of osteoporosis and pathologic fractures frequently reported in patients following organ transplantation is still not known. In two experiments, the effects of immunosuppressive drugs were studied on growing rats allocated randomly into five groups of eight rats each which received either FK506 (1.5 mg/kg or 3 mg/kg) or cyclosporine A (15 mg/kg or 30 mg/kg) for 28 days by daily oral gavage.

Dexamethasone stimulates very low density lipoprotein (VLDL) receptor gene expression in differentiating 3T3-L1 cells.

To characterize endocrine mechanisms of very low density lipoprotein (VLDL) receptor regulation we studied mouse adipocytic 3T3-L1 cells. Lipid filled adipocyte-like cells are formed during a 5-7 day time course in the presence of insulin, dexamethasone and isobutylmethylxanthine (IBMX). The VLDL receptor protein, in the form of its approximately 120 and approximately 100 kDa type I and type II isoforms, as well as binding of (125)I-beta-VLDL, was induced several-fold during differentiation.

Prolonged stimulation of the adrenals by corticotropin suppresses hepatic low-density lipoprotein and high-density lipoprotein receptors and increases plasma cholesterol.

Pituitary ACTH has been shown to strongly stimulate adrenal receptors for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) scavenger receptor class B type 1(SR-BI) to provide precursor cholesterol for glucocorticoid synthesis. The present study aimed to determine the effects of ACTH on hepatic cholesterol metabolism and plasma lipoproteins. Treatment of Sprague Dawley rats or normal C57BL/6J mice with ACTH for 3.