Markers of inflammation and fat distribution following weight loss in African-American and white women.

Changes in markers of inflammation (MOI) and fat distribution with weight loss between African-American (AA) and white (W) women have yet to be characterized. The purpose of this study was to examine potential ethnic differences in MOI and regional fat distribution with weight loss, and identify the associations between these markers and changes in regional fat distribution with weight loss among AA and W women. Subjects were 126 healthy, premenopausal women, BMI 27-30 kg/m(2). They were placed on a weight-loss intervention consisting of diet and/or exercise until a BMI <25 was achieved. Fat distribution was measured with computed tomography, and body composition with dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor-α (TNF-α), soluble TNF receptor-I (sTNFR-I), sTNFR-II, C-reactive protein (CRP), and interleukin-6 (IL-6) were assessed. All MOI and adiposity measures significantly decreased with weight loss. Significant ethnic differences with weight loss were observed for fat mass, body fat, intra-abdominal adipose tissue (IAAT), sTNFR-I, and sTNFR-II. Mixed-model analysis indicated that adjusting for change in IAAT explained ethnic differences in change in TNF-α and the decrease in TNF-α with weight loss, while total fat mass only explained the decrease in sTNFR-I and sTNFR-II with weight loss. In conclusion, all MOI decreased following weight loss among W, whereas only IL-6 and CRP decreased following weight loss in AA. The most distinct phenotypic difference observed was a greater impact of weight loss on TNF-α in W compared to AA, which was directly associated with IAAT in W.

Effect of diet with and without exercise training on markers of inflammation and fat distribution in overweight women.

The independent effects of exercise and weight loss on markers of inflammation (MOI) in obese individuals have not been clearly characterized. The objectives of this study were to: (i) identify the independent effects of exercise and weight loss on MOI and (ii) determine whether changes in MOI were associated with changes in fat distribution. Subjects were 126 healthy, premenopausal women, BMI 27-30 kg/m(2). They were randomized to one of three groups: diet only, diet + aerobic-, or diet + resistance training until a BMI <25 kg/m(2) was achieved. Fat distribution was measured with computed tomography, and body composition with dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor (TNF)-α, soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), C-reactive protein (CRP), and interleukin (IL)-6 were assessed. Results of repeated-measures ANOVA indicated a significant effect of time on MOI, such that MOI decreased with weight loss. Results of mixed-model analysis indicated that adjusting for intra-abdominal adipose tissue (IAAT) and total fat mass explained the decreases in TNF-α and sTNF-R1, whereas only total fat mass explained the decreases in sTNF-R2, IL-6, and CRP. In conclusion, weight loss was associated with decreases in MOI. The effect of weight loss appeared to be mediated by changes in total fat mass or IAAT. Addition of exercise did not alter the response, suggesting that weight loss has a more profound impact for reducing MOI in overweight women than exercise.

Effect of diabetes on enzymes involved in rat hepatic corticosterone production.

BACKGROUND: Numerous studies have explored the etiologic or permissive role of 11ß-hydroxysteroid dehydrogenase (11ß-HSD1) in obesity and Type 2 diabetes, biochemical conditions often with concurrent hyperinsulinism. In contrast, there are limited data on the effect of insulin deficiency (i.e. Type 1 diabetes) on 11ß-HSD1 or endoplasmic reticulum enzymes that generate the reduced pyridine cofactor NADPH. Thus, the aim of the present study was to examine the effect of insulin-deficient, streptozotozin diabetes on key microsomal enzymes involved in rat hepatic corticosterone production. METHODS: After rats had been rendered diabetic with streptozotocin and some had been treated with insulin (2-6 units, s.c., long-acting insulin once daily) for 7 days, hepatic microsomes were isolated. Serum corticosterone and fructosamine were obtained premortem. Intact microsomes were incubated in vitro and 11ß-HSD1, hexose-6-phosphate dehydrogenase (H6PDH), and isocitrate dehydrogenase (IDH) measured. RESULTS: Although diabetes markedly altered body weight gain and serum protein glycosylation (assessed by fructosamine), there was no significant change in hepatic 11ß-HSD1 reductase activity, with or without insulin treatment. However, serum corticosterone levels were significantly correlated with 11ß-HSD1 reductase activity when all groups were analyzed together (P < 0.05). Untreated diabetes modified (P < 0.01) two hepatic microsomal NADPH-generating enzymes, namely H6PDH and IDH, resulting in a 37% decrease and 14% increase in enzyme levels, respectively. CONCLUSIONS: Consistent with most in vivo studies, chronic insulin deficiency with attendant hyperglycemia does not significantly modify hepatic 11ß-HSD1 reductase activity, but does alter the activity of two microsomal enzymes coupled with pyridine cofactors.

Respiratory quotient predicts fat mass gain in premenopausal women.

High respiratory quotient (RQ) has been associated with fat mass (FM) gain in some, but not all studies. Variability among results may reflect differences in the RQ variable measured (fasting vs. 24-h) or may be due to differences in control for factors that affect RQ, such as diet, energy balance, circulating insulin, and insulin sensitivity. The objective of this study was to determine whether different RQ values (fasting, sleeping, nonsleeping, and 24-h) would predict change in FM over 2 years in obesity-prone women, controlling for diet and adjusting for energy balance, circulating insulin, and insulin sensitivity. Participants were 33 previously overweight premenopausal women. Fasting, sleeping, nonsleeping, and 24-h RQ values were measured during controlled-diet conditions by respiratory chamber calorimetry. Intravenous glucose tolerance tests were also performed to adjust for fasting insulin, acute insulin response to glucose, and insulin sensitivity. Over the following 2 years, changes in FM were tracked annually by dual energy X-ray absorptiometry. High nonsleeping RQ (NSRQ) predicted 2-year change in FM independently of energy balance, circulating insulin, and insulin sensitivity. This observation suggests that low postprandial fat oxidation may uniquely predispose obesity-prone individuals to accrual of adipose tissue.

Effect of estrogen on mitochondrial function and intracellular stress markers in rat liver and kidney following trauma-hemorrhagic shock and prolonged hypotension.

Trauma-hemorrhage (T-H) is known to impair tissue perfusion, leading to tissue hypoxia, and thus affecting mitochondria, the organelles with the highest oxygen demand. In a model of T-H and prolonged hypotension without fluid resuscitation, administration of a small volume of 17beta-estradiol (E2), but not vehicle, prolonged the survival of rats for 3 h, even in the absence of fluid resuscitation. The main finding of this study is that T-H followed by prolonged hypotension significantly affects mitochondrial function, endoplasmic reticulum (ER) stress markers and free iron levels, and that E2 ameliorated all these changes. All of these changes were observed in the liver but not in the kidney. The sensitivity of mitochondrial respiration to exogenous cytochrome c can reflect increased permeability of the outer mitochondrial membrane for cytochrome c. Increased levels of free iron are indicative of oxidative stress, but neither oxidative nor nitrosylative stress markers changed. The spliced isoform of XBP1 mRNA (an early marker of ER stress) and the expression of C/EBP homologous protein (CHOP) (a protein regulating ER stress-induced apoptosis) were elevated in T-H animals but remained unchanged if T-H rats received E2. Both the prevention of elevated sensitivity of mitochondrial respiration to cytochrome c and a decrease in ER stress by E2 maintain functional integrity of the liver and may help the organ during prolonged hypotension and following resuscitation. A decrease in free iron levels by E2 is more relevant for resuscitation, often accompanied by oxidative stress reaction. Thus, E2 appears to be a novel hormonal adjunct that prolongs permissive hypotension during lengthy transportation of the injured patient between the injury site and the hospital in both civilian and military injuries.

Insulin sensitivity in African-American and white women: association with inflammation.

Whether the contribution of inflammation to risk for chronic metabolic disease differs with ethnicity is not known. The objective of this study was to determine: (i) whether ethnic differences exist in markers of inflammation and (ii) whether lower insulin sensitivity among African Americans vs. whites is due to greater inflammatory status. Subjects were African-American (n = 108) and white (n = 105) women, BMI 27-30 kg/m(2). Insulin sensitivity was assessed with intravenous glucose tolerance test and minimal modeling; fat distribution with computed tomography; body composition with dual-energy X-ray absorptiometry; markers of inflammation (tumor necrosis factor (TNF)-alpha, soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2, C-reactive protein (CRP), and interleukin (IL)-6) with enzyme-linked immunosorbent assay (ELISA). Whites had greater intra-abdominal adipose tissue (IAAT), insulin sensitivity, and concentrations of TNF-alpha, sTNFR-1, and sTNFR-2 than African Americans. Greater TNF-alpha in whites vs. African Americans was attributed to greater IAAT in whites. Among whites, but not African Americans, CRP was independently and inversely associated with insulin sensitivity, after adjusting for IAAT (r = -0.29 P < 0.05, and r = -0.13 P = 0.53, respectively). Insulin sensitivity remained lower in African Americans after adjusting for CRP (P < 0.001). In conclusion, greater IAAT among whites may be associated with greater inflammation. Insulin sensitivity was lower among African Americans, independent of obesity, fat distribution, and inflammation.