PCR arrays indicate that the expression of extracellular matrix and cell adhesion genes in human adipocytes is regulated by IL-1β (interleukin-1β)

The role of IL-1β in regulating the expression of extracellular matrix (ECM) and cell adhesion genes in human adipocytes has been examined. Adipocytes differentiated in culture were incubated with IL-1β for 4 or 24 h and RNA probed with PCR arrays for 84 ECM and cell adhesion genes. Treatment with IL-1β resulted in changes in the expression at one or both time points of ~50% of the genes probed by the arrays, the majority being down-regulated. Genes whose expression was down-regulated by IL-1β included those encoding several collagen chains and integrin subunits. In contrast, IL-1β induced substantial increases (>10-fold) in the expression of ICAM1, VCAM1, MMP1 and MMP3; the secretion of the encoded proteins was also markedly stimulated. IL-1β has a pervasive effect on the expression of ECM and cell adhesion genes in human adipocytes, consistent with the derangement of tissue structure during inflammation in white fat

PCR array and protein array studies demonstrate that IL-1β (interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes

The role of IL-1β in regulating the expression and secretion of cytokines and chemokines by human adipocytes was examined. Adipocytes were incubated with human IL-1β for 4 or 24 h. The expression of a panel of 84 cytokine/chemokine genes was probed using PCR arrays. IL-1β stimulated the expression of >30 cytokine/chemokine genes on the arrays; 15 showed >100-fold increases in mRNA at 4 or 24 h including CSF3, CXCL1, CXCL2, CXCL12 and IL8. CSF3 exhibited a 10,000-fold increase in mRNA at 4 h. ADIPOQ was among the genes whose expression was inhibited. Protein arrays were used to examine the secretion of cytokines/chemokines from adipocytes. IL-1β stimulated the secretion of multiple cytokines/chemokines including MCP-1, IL-8, IP-10, MIP-1α and MCP-4. The most responsive was IP-10, which exhibited a 5,000-fold increase in secretion with IL-1β. IL-1β is likely to play a substantial role in stimulating the inflammatory response in human adipocytes in obesity

Geometry-controlled kinetics

It has long been appreciated that transport properties can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target -- the first-passage time (FPT). Although essential to quantify the kinetics of reactions on all time scales, determining the FPT distribution was deemed so far intractable. Here, we calculate analytically this FPT distribution and show that transport processes as various as regular diffusion, anomalous diffusion, diffusion in disordered media and in fractals fall into the same universality classes. Beyond this theoretical aspect, this result changes the views on standard reaction kinetics. More precisely, we argue that geometry can become a key parameter so far ignored in this context, and introduce the concept of "geometry-controlled kinetics". These findings could help understand the crucial role of spatial organization of genes in transcription kinetics, and more generally the impact of geometry on diffusion-limited reactions.Comment: Submitted versio

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

The G-308A variant of the Tumor Necrosis Factor-α (TNF-α) gene is not associated with obesity, insulin resistance and body fat distribution

BACKGROUND: Tumor Necrosis Factor-α (TNF-α) has been implicated in the pathogenesis of insulin resistance and obesity. The increased expression of TNF-α in adipose tissue has been shown to induce insulin resistance, and a polymorphism at position -308 in the promoter region ofTNF-α has been shown to increase transcription of the gene in adipocytes. Aim of this study is to investigate the role of the G-308A TNFα variant in obesity and to study the possible influence of this mutation on body fat distribution and on measures of obesity (including Fat Free Mass, Fat Mass, basal metabolic rate), insulin resistance (measured as HOMA(IR)), and lipid abnormalities. The G-308A TNFα polymorphism has been studied in 115 patients with obesity (mean BMI 33.9 ± 0.5) and in 79 normal lean subjects (mean BMI 24.3 ± 0.3). METHODS: The G-308A variant, detected by PCR amplification and Nco-1 digestion, determines the loss of a restriction site resulting in a single band of 107 bp [the (A) allele]. RESULTS: The (A) allele frequencies of the G-308A TNFα polymorphism were 13.1% in the obese group and 14.6% in the lean subjects, with no significant difference between the two groups. Furthermore, no association was found with BMI classes, body fat distribution, HOMA(IR), and metabolic abnormalities. CONCLUSIONS: Our study did not detect any significant association of the G-308A TNFα polymorphism with obesity or with its clinical and metabolic abnormalities in this population. Our data suggests that, in our population, the G-308A TNFα polymorphism is unlikely to play a major role in the pathogenesis of these conditions

Notch1 deficiency decreases hepatic lipid accumulation by induction of fatty acid oxidation

Notch signaling pathways modulate various cellular processes, including cell proliferation, differentiation, adhesion, and communication. Recent studies have demonstrated that Notch1 signaling also regulates hepatic glucose production and lipid synthesis. However, the effect of Notch1 signaling on hepatic lipid oxidation has not yet been directly investigated. To define the function of Notch1 signaling in hepatic lipid metabolism, wild type mice and Notch1 deficient antisense transgenic (NAS) mice were fed a high-fat diet. High-fat diet-fed NAS mice exhibited a marked reduction in hepatic triacylglycerol accumulation compared with wild type obese mice. The improved fatty liver was associated with an increased expression of hepatic genes involved in fatty acid oxidation. However, lipogenic genes were not differentially expressed in the NAS liver, suggesting lipolytic-specific regulatory effects by Notch1 signaling. Expression of fatty acid oxidative genes and the rate of fatty acid oxidation were also increased by inhibition of Notch1 signaling in HepG2 cells. In addition, similar regulatory effects on lipid accumulation were observed in adipocytes. Taken together, these data show that inhibition of Notch1 signaling can regulate the expression of fatty acid oxidation genes and may provide therapeutic strategies in obesity-induced hepatic steatosisopen0

Design of the New Life(style) study: a randomised controlled trial to optimise maternal weight development during pregnancy. [ISRCTN85313483]

BACKGROUND: Preventing excessive weight gain during pregnancy is potentially important in the prevention of overweight and obesity among women of childbearing age. However, few intervention studies aiming at weight management during pregnancy have been performed and most of these interventions were not as successful as expected. In this paper the design of the New Life(style) study is described as well as the content of the individually tailored intervention program, which focuses on controlling weight development during pregnancy. METHODS: The effectiveness of the New Life(style) intervention program versus usual care by midwives is evaluated in a randomised controlled trial. Women who expect their first child and visit one of the participating midwifery practices are included. The intervention is standardised in a protocol and executed by trained counsellors with the women who are randomised in the intervention group. During 5 sessions – at 18, 22, 30 and 36 weeks of pregnancy and at 8 weeks postpartum – individual weight gain is discussed in relation to weight gain guidelines for pregnant women of the American Institute of Medicine. Counsellors coach the women to maintain or optimise a healthy lifestyle, in a period of drastic physical and mental changes. Data is collected at 15, 25, 35 weeks of pregnancy and at 6, 26, and 52 weeks after delivery. Primary outcome measures are body weight, BMI, and skinfold thickness. Secondary outcome measures include physical activity, nutrition and blood levels of factors that are associated with energy homeostasis. DISCUSSION: Results of the current RCT will improve the knowledge of determinants of weight gain during pregnancy, weight retention after childbirth and of the effectiveness of the intervention program that is described. Caregivers and researchers in the field of health promotion are offered more insight in specific elements of the New Life(style) intervention program