American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Mar 2007
Monocyte chemoattractant protein-1 influences trauma-hemorrhage-induced distal organ damage via regulation of keratinocyte-derived chemokine production.
Leukocyte infiltration, mediated by chemokines, is a key step in the development of organ dysfunction. Lung and liver neutrophil infiltration following trauma-hemorrhage is associated with upregulation of monocyte chemoattractant protein-1 (MCP-1). Because MCP-1 is not a major attractant for neutrophils, we hypothesized that MCP-1 influences neutrophil infiltration via regulation of keratinocyte-derived chemokines (KC). ⋯ This decrease in MCP-1 levels was associated with decreased neutrophil infiltration and edema formation in lung and liver following trauma-hemorrhage. Restitution of KC in mice treated with MCP-1 antiserum restored tissue neutrophil infiltration and edema. These results lead us to conclude that increased levels of MCP-1 cause neutrophil accumulation and distant organ damage by regulating KC production during the postinjury inflammatory response.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Feb 2007
Leptin antagonist reveals that the normalization of caloric intake and the thermic effect of food after high-fat feeding are leptin dependent.
High-fat (HF) feeding induces a transient increase in caloric intake and enhances energy expenditure. We hypothesized that leptin is necessary for homeostatic restoration of the HF-enhanced caloric intake and may mediate the increase in uncoupling protein-1 (UCP1) in brown adipose tissue (BAT). We employed a leptin antagonist to examine the role of leptin in these biological processes. ⋯ HF feeding elevated caloric intake, which nearly normalized by day 7, whereas in the presence of the antagonist, caloric intake remained elevated. Moreover, the HF-mediated augmentation in UCP1 in BAT was prevented by the antagonist. These results demonstrate that leptin is essential for the homeostatic restoration of caloric intake after HF feeding and that this leptin antagonist is able to block central leptin signaling and leptin-mediated UCP1 elevation.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Jan 2007
Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss.
Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. ⋯ Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Jan 2007
The median preoptic nucleus is involved in the facilitation of heat-escape/cold-seeking behavior during systemic salt loading in rats.
Systemic salt loading has been reported to facilitate operant heat-escape/cold-seeking behavior. In the present study, we hypothesized that the median preoptic nucleus (MnPO) would be involved in this mechanism. Rats were divided into two groups (n = 6 each): one group had the MnPO lesion with ibotenic acid (4.0 mug) and the other was the vehicle control. ⋯ However, in the MnPO-lesion group, counts of the behavior were similar between the hypertonic- and isotonic-saline injection trials (10 +/- 2 and 8 +/- 1 at 35 degrees C, and 17 +/- 1 and 16 +/- 1 at 40 degrees C, respectively). T(core) increased (P < 0.05) in the heat in both trials (36.8 +/- 0.1 degrees C and 37.4 +/- 0.1 degrees C at 26 degrees C and 37.4 +/- 0.2 degrees C and 37.8 +/- 0.2 degrees C at 40 degrees C in the hypertonic- and isotonic-saline injection trials, respectively). These results may suggest that, at least in part, the MnPO is involved in the facilitation of heat-escape/cold-seeking behavior during osmotic stimulation.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Nov 2006
Deficiency of gammadelta T lymphocytes contributes to mortality and immunosuppression in sepsis.
Studies have indicated that gammadelta T lymphocytes play an important role in the regulation of immune function and the clearance of intracellular pathogens. We have recently reported that intraepithelial lymphocytes (IEL), which are rich in gammadelta T cells, within the small intestine illustrated a significant increase in apoptosis and immune dysfunction in mice subjected to sepsis. However, the contribution of gammadelta T cells to the host response to polymicrobial sepsis remains unclear. ⋯ Whereas T helper (Th)1 cytokine release by anti-CD3-stimulated splenocytes was significantly depressed in septic gammadelta+/+ mice, there was no such depression in gammadelta-/- mice. However, gammadelta T cell deficiency had no effect on Th2 cytokine release. These findings suggest that gammadelta T cells may play a critical role in regulating the host immune response and survival to sepsis, in part by alteration of the level of IEL CD8+gammadelta+ T cells and through the development of the Th1 response.