American journal of physiology. Endocrinology and metabolism
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Am. J. Physiol. Endocrinol. Metab. · May 2009
Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase.
Acylated (octanoylated) ghrelin stimulates food intake and growth hormone secretion and is deacylated into desacyl ghrelin by butyrylcholinesterase. Acylated and desacyl ghrelin both promote adipogenesis. Ghrelin concentrations decrease with hyperglycemia and hyperinsulinism. ⋯ Circulating octanoate concentrations (3.1 +/- 0.5 vs. 4.5 +/- 0.6 microg/ml, P = 0.029) and cholinesterase activity (705 +/- 33 vs. 1,013 +/- 56 U/ml, P < 0.001) were lower during pregnancy compared with the postpartum period. In conclusion, acylated ghrelin markedly decreases during pregnancy, likely because of a decrease in the acylation process. Desacyl ghrelin increases in gestational diabetes, possibly reflecting resistance to the inhibitory effect of insulin on ghrelin secretion.
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Am. J. Physiol. Endocrinol. Metab. · May 2009
The Lou/C rat: a model of spontaneous food restriction associated with improved insulin sensitivity and decreased lipid storage in adipose tissue.
The inbred Lou/C rat, originating from the Wistar strain, has been described as a model of resistance to diet-induced obesity, but little is known about its metabolism. Since this knowledge could provide some clues about the etiology of obesity/insulin resistance, this study aimed at characterizing glucose and lipid metabolism in Lou/C vs. Wistar rats. ⋯ In the inguinal adipose depot, expression of uncoupling protein-1 was detected in Lou/C but not in Wistar rats, in keeping with a higher expression of peroxisome proliferator-activated receptor-gamma coactivator-1 in these animals. The Lou/C rat is a valuable model of spontaneous food restriction with associated improved insulin sensitivity. Independently from its reduced caloric intake, it also exhibits a preferential channeling of nutrients toward utilization rather than storage.
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Am. J. Physiol. Endocrinol. Metab. · Feb 2009
Comparative StudyPathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis.
The objective was to examine pathways of androgen metabolism in abdominal adipose tissue in women. Abdominal subcutaneous (SC) and omental (OM) adipose tissue samples were surgically obtained in women. Total RNA was isolated from whole adipose tissue samples and from primary preadipocyte cultures before and after induction of differentiation. ⋯ DHT inactivation rates increased with differentiation, this effect being mediated by dexamethasone alone, through a glucocorticoid receptor-dependent mechanism. In conclusion, higher mRNA levels of enzymes synthesizing and inactivating androgens are found in differentiated adipocytes, consistent with higher androgen-processing rates in these cells. Glucocorticoid-induced androgen inactivation may locally modulate the exposure of adipose cells to active androgens.
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Am. J. Physiol. Endocrinol. Metab. · Jan 2009
Palmitate- and lipopolysaccharide-activated macrophages evoke contrasting insulin responses in muscle cells.
Factors secreted by macrophages contribute to whole body insulin resistance, acting in part on adipose tissue. Muscle is the major tissue for glucose disposal, but how macrophage-derived factors impact skeletal muscle glucose uptake is unknown, or whether the macrophage environment influences this response. We hypothesized that conditioned medium from macrophages pretreated with palmitate or LPS would directly affect insulin action and glucose uptake in muscle cells. ⋯ Furthermore, depending on their environment, macrophages negatively or positively influence muscle cells. Macrophages exposed to palmitate produce a mixture of proinflammatory cytokines that reduce insulin action in muscle cells; conversely, LPS-activated macrophages increase insulin action, likely via IL-10. Macrophages may be an integral element in glucose homeostasis in vivo, relaying effects of circulating factors to skeletal muscle.
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Am. J. Physiol. Endocrinol. Metab. · Dec 2008
Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-alpha and angiotensin II by beta-hydroxy-beta-methylbutyrate.
Both tumor necrosis factor-alpha (TNF-alpha)/interferon-gamma (IFN-gamma) and angiotensin II (ANG II) induced an increase in total protein degradation in murine myotubes, which was completely attenuated by treatment with beta-hydroxy-beta-methylbutyrate (HMB; 50 microM). There was an increase in formation of reactive oxygen species (ROS) within 30 min, as well as an increase in the activity of both caspase-3 and -8, and both effects were attenuated by HMB. Moreover, inhibitors of caspase-3 and -8 completely attenuated both ROS formation and total protein degradation induced by TNF-alpha/IFN-gamma and ANG II. ⋯ Activation of p38 MAPK by PKR provides the link to ROS formation. These results suggest that TNF-alpha/IFN-gamma and ANG II induce muscle protein degradation by a common signaling pathway, which is attenuated by HMB, and that this involves the initial activation of caspase-3 and -8, followed by autophosphorylation and activation of PKR, which then leads to increased ROS formation via activation of p38 MAPK. Increased ROS formation is known to induce protein degradation through the ubiquitin-proteasome pathway.