OBJECTIVE -The primary objective was to examine whether the combination of diet and aerobic exercise (DA) or diet and resistance exercise (DR) is associated with greater improvements in metabolic risk factors by comparison to diet only (DO) in obese women. A second objective considered whether reductions in metabolic risk factors are related to concurrent changes in abdominal and/or intermuscular fat distribution. RESEARCH DESIGN AND METHODS-A total of 38 premenopausal obese women were randomly assigned to one of three 16-week treatments: DO (n ϭ 13), DA (n ϭ 11), or DR (n ϭ 14). Plasma glucose, insulin, and lipid levels were measured in a fasting state and after a 75-g oral glucose challenge (oral glucose tolerance test [OGTT]). Total, abdominal subcutaneous, visceral, and intermuscular fat were measured by magnetic resonance imaging.RESULTS -Significant reductions (P Ͻ 0.02) in body weight (ϳ10 kg or 10%) and in total, abdominal subcutaneous, visceral, and intermuscular fat were observed within each group. Fasting and OGTT insulin, total cholesterol, LDL cholesterol, and apolipoprotein B also decreased within each group (P Յ 0.02). The changes in the body fat and metabolic variables were not different across treatment (P Ͼ 0.05). Visceral fat alone was related to the metabolic risk factors both before and after the treatment.CONCLUSIONS -Weight loss was associated with reductions in metabolic risk factors in obese women. The improvement in the metabolic profile was not enhanced by the addition of aerobic or resistance exercise. The findings reinforce the importance of diminished visceral fat in the treatment of insulin resistance. Diabetes Care 25:431-438, 2002T he prevalence of obesity and associated comorbidities is increasing (1,2), which underscores the importance of developing effective strategies for reducing obesity and the risk of metabolic disease in women. Diet-induced weight loss (3-5) as well as aerobic exercise (6 -8) and resistance exercise (7-9) are effective treatments for reducing metabolic risk factors in women. Although these observations suggest that the combination of diet and exercise would have a greater effect on metabolic risk factors than weight loss alone, the influence of diet and exercise combined in women is unclear. Whereas some studies report greater improvements in the plasma lipid profile in response to the combination of diet and exercise than diet alone (10 -12), others report no treatment differences (13-15). It is also reported that the addition of aerobic (16,17) or resistance (16) exercise does not enhance the reductions in plasma insulin and glucose levels in comparison to diet alone in obese women. These observations do not reflect those in a recent report in obese men wherein a twofold greater improvement in insulin action was observed in response to diet combined with aerobic or resistance exercise than diet alone (18). A rationale that explains the equivocal findings is unknown; however, taken together, these observations suggest that the utility of exercise to enha...

Murine invariant natural killer T (iNKT) cells provide cognate and non-cognate help for lipid and protein-specific B cells, respectively. However, the long term B cell outcome following cognate iNKT help is currently unknown. We show that cognate iNKT cell help resulted in a B cell differentiation program characterized by extrafollicular plasmablasts, germinal center formation, affinity maturation and a robust primary IgG antibody response that was uniquely dependent on iNKT-derived interleukin 21 (IL-21). However, cognate iNKT cell help did not generate an enhanced humoral memory response. Thus, iNKT cell cognate help for lipid-specific B cells induces a unique signature which is a hybrid of classic T-dependent (TD) and T-independent type 2 (TI-2) B cell responses.

The live vaccine strain (LVS) ofFrancisella tularensis caused lethal disease in several mouse strains. Lethality depended upon the dose and route of inoculation. The lethal dose for 50% of the mice (LD50) in four of six mouse strains (A/J, BALB/cHSD, C3H/HeNHSD, and SWR/J) given an intraperitoneal (i.p.) inoculation was less than 10 CFU. For the other two strains tested, C3H/HeJ and C57BL/6J, the i.p. log LD5* was 1.5 and 2.7, respectively. Similar susceptibility was observed in mice inoculated by intravenous (i.v.) and intranasal (i.n.) routes: in all cases the LD50 was less than 1,000 CFU. Regardless of the inoculation route (i.p., i.v., or i.n.), bacteria were isolated from spleen, liver, and lungs within 3 days of introduction of bacteria; numbers of bacteria increased in these infected organs over 5 days. In contrast to the other routes of inoculation, mice injected with LVS intradermally (i.d.) survived infection: the LD50 of LVS by this route was much greater than 105 CFU. This difference in susceptibility was not due solely to local effects at the dermal site of inoculation, since bacteria were isolated from the spleen, liver, and lungs within 3 days by this route as well. The i.d.-infected mice were immune to an otherwise lethal i.p. challenge with as many as 104 CFU, and immunity could be transferred with either serum, whole spleen cells, or nonadherent spleen cells (but not Ig+ cells). A variety of infectious agents induce different disease syndromes depending on the route of entry. Francisella LVS infection in mice provides a model system for analysis of locally induced protective effector mechanisms.

To our knowledge, this is the first report that PSA may function in tumors as an endogenous antiangiogenic protein. This function may explain, in part, the naturally slow progression of prostate cancer. Our findings call into question various strategies to inhibit the expression of PSA in the treatment of prostate cancer.

Similar to Ipaf and caspase-1, the Nod-like receptor protein Naip5 restricts intracellular proliferation of Legionella pneumophila, the causative agent of a severe form of pneumonia known as Legionnaires’ disease. Thus, Naip5 has been suggested to regulate Legionella replication inside macrophages through the activation of caspase-1. In this study, we show that cytosolic delivery of recombinant flagellin activated caspase-1 in A/J macrophages carrying a mutant Naip5 allele, and in C57BL/6 (B6) macrophages congenic for the mutant Naip5 allele (B6-Naip5A/J), but not in Ipaf−/− cells. In line with these results, A/J and B6-Naip5A/J macrophages induced high levels of caspase-1 activation and IL-1β secretion when infected with Legionella. In addition, transgenic expression of a functional Naip5 allele in A/J macrophages did not alter Legionella-induced caspase-1 activation and IL-1β secretion. Notably, defective Naip5 signaling renders B6-Naip5A/J macrophages permissive for Legionella proliferation despite normal caspase-1 activation. These results indicate that the restriction of intracellular Legionella replication is more complex than previously appreciated and requires both Ipaf-dependent caspase-1 activation as well as functional Naip5 signaling.