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Maternal food restriction during pregnancy results in intrauterine growth-restricted (IUGR) newborns with significantly decreased plasma leptin levels. When nursed by ad libitum-fed controls, IUGR offspring exhibit hyperphagia with adult obesity, marked by increased percentage body fat and plasma leptin, suggesting altered anorexigenic pathways. The authors(More)
OBJECTIVE The adipocyte-derived hormone leptin regulates food intake and body weight via the activation of JAK-STAT pathway in mammalian adult hypothalamic neurons. To investigate whether endogenous leptin is metabolically active in newborn rat pups, the JAK-STAT leptin signaling pathway was analyzed following leptin antagonist challenge. METHODS One day(More)
BACKGROUND Small for gestational age (SGA) leads to increased risk of adult obesity and metabolic syndrome. Offspring exposed to 50% maternal food restriction in utero are born smaller than Controls (FR), catch-up in growth by the end of the nursing period, and become obese adults. The objective of the study was to determine stearoyl-CoA desaturase activity(More)
UNLABELLED BACKGROUND Small-for-gestational age (SGA) at birth increases risk of development of adult obesity and insulin resistance. A model of SGA rat offspring has been shown to exhibit increased adipose tissue expression of a key adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), and increased fatty acid de(More)
OBJECTIVE We determined the potential programming effects of maternal obesity and high-fat (HF) diet during pregnancy and/or lactation on offspring metabolic syndrome. STUDY DESIGN A rat model of maternal obesity was created using an HF diet prior to and throughout pregnancy and lactation. At birth, pups were cross-fostered, thereby generating 4 paradigms(More)
Nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) cross talk and serve as xenobiotic sensors to form a safety net against the toxic effects of harmful substances. Retinoid x receptor alpha (RXRalpha) dimerizes with CAR and PXR. In order to analyze the role of RXRalpha in these xeno-sensor-mediated pathways, hepatocyte(More)
OBJECTIVE A maternal high-fat diet creates an increased risk of offspring obesity and systemic hypertension. Although the renal renin-angiotensin system (RAS) is known to regulate blood pressure, it is now recognized that the RAS is also activated in adipose tissue during obesity. We hypothesized that programmed offspring hypertension is associated with the(More)
Pulmonary fibrosis is a common delayed side effect of radiation therapy. Since its mechanism is almost unknown, little can be done to prevent or treat it. Th2 cytokines have been clearly implicated as mediators of asthma, and evidence is mounting that type 2 immune responses may also promote the development of pulmonary fibrosis. The aim of this study was(More)
The usefulness of human telomerase reverse transcriptase (hTERT) gene promoter has been proposed in cancer-targeted gene therapy. However, this promoter may not be strong enough to achieve therapeutic levels of transgene expression. In this study, we tested an 'indirected-activator' strategy that utilizes radiation to increase the activity of the hTERT gene(More)
The classical and alternative activation of macrophages has been proposed to play a role in radiation-induced pneumonitis and fibrosis, respectively. To test this hypothesis, the thoraces of C57BL/6 mice were irradiated with 12 Gy X-rays, and irradiated and control mice were euthanized at 1, 8, 12, 24 and 72 hours, and 2, 4, 8, 16 and 24 weeks after(More)