Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude

AIM: To use leptin-deficient (ob/ob) mice with demonstrated differences in steatosis levels to test a new diagnostic method using the acoustical structure quantification (ASQ) mode and the associated analytical parameter, “focal disturbance ratio” (FD-ratio).METHODS: Nine ob/ob mice, at 5, 8, and 12 wk of age (n = 3 in each age group), were used as models for hepatic steatosis. Echo signals obtained from ultrasonography in the mice were analyzed by ASQ, which uses a statistical analysis of echo amplitude to estimate inhomogeneity in the diagnostic region. FD-ratio, as calculated from this analysis, was the focus of the present study. FD-ratio and fat droplet areas and sizes were compared between age groups.RESULTS: No fibrosis or inflammation was observed in any of the groups. The fat droplet area significantly (P < 0.01) increased with age from 1.25% ± 0.28% at 5 wk to 31.07% ± 0.48% at 8 wk to 51.69% ± 3.19% at 12 wk. The median fat droplet size also significantly (P < 0.01) increased with age, from 1.33 (0.55-10.52) μm at 5 wk, 2.82 (0.61-44.13) μm at 8 wk and 6.34 (0.66-81.83) μm at 12 wk. The mean FD-ratio was 0.42 ± 0.11 at 5 wk, 0.11 ± 0.05 at 8 wk, and 0.03 ± 0.02 at 12 wk. The FD-ratio was significantly lower at 12 wk than at 5 wk and 8 wk (P < 0.01). A significant negative correlation was observed between the FD-ratio and either the fat droplet area (r = -0.7211, P = 0.0017) or fat droplet size (r = -0.9811, P = 0.0052).CONCLUSION: This tool for statistical analysis of signals from ultrasonography using the FD-ratio can be used to accurately quantify fat in vivo in an animal model of hepatic steatosis, and may serve as a quantitative biomarker of hepatic steatosis.     

Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a~(-/-) mice

AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P 0.05) serum levels of IL-10(4.6 ± 2 vs 19.4 ± 4), CXCL9(1319.0 ± 277 vs 3901.0 ± 858), and TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P 0.05) in P. vulgaris-treated mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P 0.05). The numbers of CD4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris-treated mdr1a-/- mice. CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a-/- mice.     

Characteristics of allergic colitis in breast-fed infants in the absence of cow’s milk allergy

AIM: To investigate the characteristics of mucosal le-sions and their relation to laboratory data and long-term follow up in breast-fed infants with allergic colitis. METHODS: In this study 31 breast-fed infants were prospectively evaluated (mean age, 17.4 wk) whose rectal bleeding had not ceased after a maternal elimi-nation diet for cow’s milk. Thirty-four age-matched and breast-fed infants (mean age, 16.9 wk) with no rectal bleeding were enrolled for laboratory testing as con-trols. Laboratory findings, colonoscopic and histological characteristics were prospectively evaluated in infants with rectal bleeding. Long-term follow-up with differ-ent nutritional regimes (L-amino-acid based formula or breastfeeding) was also included. RESULTS: Iron deficiency, peripheral eosinophilia andthrombocytosis were significantly higher in patients with allergic colitis in comparison to controls (8.4±3.2 μmol/L vs 13.7±4.7 μmol/L, P<0.001; 0.67±0.49 G/L vs 0.33±0.17 G/L, P<0.001; 474±123 G/L vs 376±89 G/L, P<0.001, respectively). At colonosco-py, lymphonodular hyperplasia or aphthous ulceration were present in 83% of patients. Twenty-two patients were given L-amino acid-based formula and 8 contin-ued the previous feeding. Time to cessation of rectal bleeding was shorter in the special formula feeding group (mean, 1.4 wk; range, 0.5-3 wk) when com-pared with the breast-feeding group (mean, 5.3 wk; range, 2-9 wk). Nevertheless, none of the patients ex-hibited rectal bleeding at the 3-mo visit irrespective of the type of feeding. Peripheral eosinophilia and cessa-tion of rectal bleeding after administration of elemental formula correlated with a higher density of mucosal eosinophils. CONCLUSION: Infant hematochezia, after cow’s milk allergy exclusion, is generally a benign and probably self-limiting disorder despite marked mucosal abnor-mality. Formula feeding results in shorter time to cessa-tion of rectal bleeding; however, breast-feeding should not be discouraged in long-lasting hematochezia.     

Vitamin D supplementation improves sustained virologic response in chronic hepatitis C （genotype 1）-nave patients

AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy.METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by real-time polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment.RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean body mass index (27 ± 4 kg/m² vs 24 ± 3 kg/m²; P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin.CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-naïve patients with chronic HCV genotype 1 infection significantly improves the viral response.     

Dietary zinc and metallothionein on small intestinal disaccharidases activity in mice

AIM: To examine the effect of increasing dietary zinc (Zn) intake and the lack of metallothionein (MT) expression on activity of small intestinal disaccharidases. METHODS: MT-Ⅰ and Ⅱ knockout (MT-/-) and wild-type (MT+/+) female mice at 3.5 wk of age were randomly fed with a diet containing 2 (2 Zn), 15 (15 Zn) or 50 (50 Zn) mg Zn/kg (n = 8/group/genotype) for 5 wk. Small intestinal segments (duodenum, jejunum and ileum) were collected and either fixed in 10% formalin for histological analysis or snap froze...     

Physical activity support or weight loss counseling for nonalcoholic fatty liver disease?

AIM:To determine the clinical effectiveness of intense psychological support to physical activity(PA)in nonalcoholic fatty liver disease(NAFLD),compared with cognitive-behavioral treatment(CBT).METHODS:Twenty-two NAFLD cases received support to exercise,tailored to their motivational needs(PA group).The effects on body weight,physical fitness[6-min walk test,VO2max and the PA-rating(PA-R)questionnaire]and body fat(fatty liver indices and visceral adiposity index)were compared with data obtained in 44 NAFLD subjects enrolled in a CBT program for weight loss,after adjustment for propensity score,calculated on baseline data.Measurements were performed at baseline,at 4-mo and one-year follow-up.Changes in anthropometric,biochemical and PA parameters were tested by repeated measurement ANOVA.Outcome results were tested by logistic regression analysis.RESULTS:At the end of the intensive program,BMI was less significantly reduced in the PA group(-1.09±1.68 kg/m2 vs-2.04±1.42 kg/m2 in the CBT group,P=0.019)and the difference was maintained at 1-year follow-up(-0.73±1.63 vs-1.95±1.88,P=0.012)(ANOVA,P=0.005).PA-R was similar at baseline,when only 14%of cases in PA and 36%in CBT(P=0.120)recorded values≥3.At 4 mo,a PA-R≥3 was registered in 91%of PA and 46%of CBT,respectively(P<0.001)and PA-R≥5(up to 3 h/wk of moderate-toheavy intensity physical activity)was registered in 41%of PA and only 9%of CBT group(P<0.007).The6-min walk test increased by 139±26 m in PA and by only 43±38 m in CBT(P<0.001)and VO2max by8.2±3.8 mL/kg per minute and 3.3±2.7 mL/kg per minute,respectively(P<0.002).After adjustment for propensity,weight loss>7%was significantly associated with CBT group at one year(OR=6.21;95%CI:1.23-31.30),whereas PA-R>3 was associated with PA group(10.31;2.02-52.63).Liver enzymes decreased to values within normal limits in 36%of PA cases and61%of CBT(P<0.070).Estimated liver fat(Kotronen index)fell below the fatty liver threshold in 36%of PA and 34%and CBT cases at one-year(not different).Also the fatty liver index and the visceral adiposity index improved to a similar extent.CONCLUSION:Intensive psychological counseling for PA produces hepatic effects not different from standard CBT,improving physical fitness and liver fat independent of weight loss.Strategies promoting exercise are worth and effective in motivated patients,particularly in lean NAFLD patients where large weight loss cannot be systematically pursued.     

Prognosticvalueofincreasedcarbohydrateantigeninpatientswithheart failure

AIM:To study the prognostic value of carbohydrateantigen 125(CA125) and whether it adds prognostic information to N-terminal pro-brain natriuretic peptide(NT-proBNP) in stable heart failure(HF) patients.METHODS:The predictive value of CA125 was retrospectively assessed in 156 patients with stable HF remitted to the outpatient HF unit for monitoring from 2009 to 2011.Patients were included in the study if they had a previous documented episode of HF and received HF treatment.CA125 and NT-proBNP concentrations were measured.The independent association between NT-proBNP or CA125 and mortality was assessed with Cox regression analysis,and their combined predictive ability was tested by the integrated discrimination improvement(IDI) index.RESULTS:The mean age of the 156 patients was 72 ± 12 years.During follow-up(17 ± 8 mo),27 patients died,1 received an urgent heart transplantation and 106 required hospitalization for HF.Higher CA125 values were correlated with outcomes:58 ± 85 KU/L if hospitalized vs 34 ± 61 KU/L if not(P 0.05),and 94 ± 121 KU/L in those who died or needed urgent heart transplantation vs 45 ± 78 KU/L in survivors(P 0.01).After adjusting for propensity scores,the highest risk was observed when both biomarkers were elevated vs not elevated(HR = 8.95,95%CI:3.11-25.73; P 0.001) and intermediate when only NT-proBNP was elevated vs not elevated(HR = 4.15,95%CI:1.41-12.24; P 0.01).Moreover,when CA125 was added to the clinical model with NT-proBNP,a 4%(P 0.05) improvement in the IDI was found.CONCLUSION:CA125 60 KU/L identified patients in stable HF with poor survival.Circulating CA125 level adds prognostic value to NT-proBNP level in predicting HF outcomes.     

Interaction between maternal and postnatal high fat diet leads to a greater risk of myocardial dysfunction in offspring via enhanced lipotoxicity,IRS-1 serine phosphorylation and mitochondrial defects

Maternal overnutrition is associated with heart diseases in adult offspring. However, combined effect of maternal and postnatal fat intake on cardiac function is unknown. This study was designed to examine the impact of maternal and postnatal fat intake on metabolic, myocardial, insulin and mitochondrial responses in adult offspring. Pregnant FVB mice were fed a low fat (LF) or high fat (HF) diet during gestation and lactation. Weaning male offspring were placed on either LF or HF (calorie-restricted HF-fed mice used as weight control) for 4 months prior to assessment of metabolic indices, myocardial histology, cardiac function, insulin signaling, mitochondrial integrity and reactive oxygen species (ROS) generation. Compared with LF- and HF-fed weight-control mice, postnatal HF intake resulted in obesity, adiposity, dyslipidemia, insulin resistance, cardiac hypertrophy, interrupted cardiac contractile, intracellular Ca^2 + and mitochondrial properties, all of which were significantly accentuated by prenatal fat exposure. Despite the preserved cardiac contractile function, LF offspring from HF-fed dams displayed higher body weights, increased adiposity and glucose intolerance. HF-fed mice with prenatal HF exposure displayed upregulated serine phosphorylation of IRS-1, PTP1B, the rate-limiting fatty acid synthesis enzyme stearoyl-CoA desaturase (SCD1) and hypertrophic markers (calcineurin A, GATA4, ANP, β-MHC and skeletal α-actin), while suppressing AMP-dependent protein kinase, glucose uptake and PGC-1α levels. Importantly, myocardial and mitochondrial ultrastructural abnormalities were more pronounced in HF-fed offspring with prenatal fat exposure, shown as loss of mitochondrial density and membrane potential, increased ROS generation and apoptosis. Our data suggest that prenatal dietary fat exposure predisposes offspring to postnatal dietary fat-induced cardiac hypertrophy and contractile defect possibly via lipotoxicity, glucose intolerance and mitochondrial dysfunction. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".     

Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice

AIM:To investigate the effect of T helper(Th)17/T regulatory(Treg)cells on hepatic fibrosis in mice and its possible mechanism.METHODS:Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride.Hepatic pathological changes were observed by hematoxylin and eosin staining;the protein levels of interleukin(IL)-6,transforming growth factor(TGF)-βandα-smooth muscle actin(SMA)in liver tissue were determined by Western blotting;and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry.In addition,hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells.Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation.RESULTS:In the model group,there were different degrees of fibroplasia,degeneration and necrosis.The protein levels of IL-6,TGF-βandα-SMA in liver tissue were significantly higher than those in the control group at 12 wk(P<0.05).Compared with the control group,the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually.Furthermore,at 4,8 and 12 wk,there were significant differences in the number of Th17 cells(0.52%±0.16%,1.46%±0.24%,and2.60%±0.41%,respectively,P<0.05)and Treg cells(2.99%±0.40%,2.16%±0.50%,and 1.49%±0.34%,respectively,P<0.05).In vitro,Th17 cells promoted,whereas Treg cells inhibited the expression ofα-SMA,both in a dose-dependent manner,compared with the control group.CONCLUSION:Th17/Treg imbalance exists in mice with liver fibrosis,which potentially promotes liver fibrosis via HSC activation.     

Combined effects of body composition and ageing on joint torque,muscle activation and co-contraction in sedentary women

This study aimed to establish the interplay between body mass, adiposity, ageing and determinants of skeletal muscle strength. One hundred and two untrained healthy women categorised by age into young (Y) (mean ± SD, 26.7 ± 9.4 years) vs. old (O) (65.1 ± 7.2 years) were assessed for body fat, lean mass, plantar flexion and dorsiflexion maximum voluntary isometric contraction (MVC) torque, muscle activation capacity and antagonist muscle co-contraction. MVC torque normalised to body mass in the obese group was 35 and 29 % lower (p < 0.05) in Y and 34 and 31 % lower (p < 0.05) in O, compared with underweight and normal weight individuals, respectively. Y with ≥40 % body fat had significantly lower activation than Y with <40 % body fat (88.3 vs. 94.4 %, p < 0.05), but O did not exhibit this effect. Co-contraction was affected by ageing (16.1 % in O vs. 13.8 % in Y, p < 0.05) but not body composition. There were significant associations between markers of body composition, age, strength and activation capacity, with the strongest correlation between muscle strength and total body mass (r² = 0.508 in Y, p < 0.001, vs. r² = 0.204 in O, p < 0.01). Furthermore, the age-related loss in plantar flexion (PF) MVC torque was exacerbated in obese compared to underweight, normal weight and overweight individuals (−0.96 vs. −0.54, −0.57 and −0.57 % per year, p < 0.05). The negative impact of adiposity on muscle performance is associated with not only muscular but also neural factors. Overall, the effects of ageing and obesity on this system are somewhat cumulative.     

Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis

AIM: To identify and characterize drosophila mothers against decapentaplegic (SMAD)3-dependent changes in immune cell populations following infection with Helicobacter hepaticus (H. hepaticus).METHODS: SMAD3^-/- (n = 19) and colitis-resistant SMAD3^+/- (n = 24) mice (8-10 wk of age) were infected with H. hepaticus and changes in immune cell populations [T lymphocytes, natural killer (NK) cells, T regulatory cells] were measured in the spleen and mesenteric lymph nodes (MsLNs) at 0 d, 3 d, 7 d and 28 d post-infection using flow cytometry. Genotype-dependent changes in T lymphocytes and granzyme B⁺ cells were also assessed after 28 d in proximal colon tissue using immunohistochemistry.RESULTS: As previously observed, SMAD3^-/-, but not SMAD3^+/- mice, developed colitis, peaking at 4 wk post-infection. No significant changes in T cell subsets were observed in the spleen or in the MsLNs between genotypes at any time point. However, CD4⁺ and CD8⁺/CD62L^lo cells, an effector T lymphocyte population, as well as NK cells (NKp46/DX5⁺) were significantly higher in the MsLNs of SMAD3^-/- mice at 7 d and 28 d post-infection. In the colon, a higher number of CD3⁺ cells were present in SMAD3^-/- compared to SMAD3^+/– mice at baseline, which did not significantly change during infection. However, the number of granzyme B⁺ cells, a marker of cytolytic lymphocytes, significantly increased in SMAD3^-/- mice 28 d post-infection compared to both SMAD3^+/- mice and to baseline values. This was consistent with more severe colitis development in these animals.CONCLUSION: Data suggest that defects in SMAD3 signaling increase susceptibility to H. hepaticus-induced colitis through aberrant activation and/or dysregulation of effector lymphocytes.     

Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

AIM: To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS: We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes. We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter (rAd-SP-rINSfur) into diabetic Lepr^db/db mice. A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control (rAd-CMV-βgal). Blood glucose levels and body weights were monitored for 50 d. Glucose and insulin tolerance tests were performed. Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS: Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d, whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic. Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve (AUC): 21  508.80 ± 2248.18 vs 62  640.00 ± 5014.28, P < 0.01] and at 6 wk (AUC: 29  956.60 ± 1757.33 vs 60  016.60 ± 3794.47, P < 0.01). In addition, insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice (AUC: 9150.17 ± 1007.78 vs 11  994.20 ± 474.40, P < 0.05). The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION: Based on these results, we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.     

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatm     

Changes in feeding efficiency and carcass composition in rats on repeated high-fat feedings

Male and female Sprague-Dawley rats were fed ad libitum two cycles of 10 weeks of a high-fat (HF) diet, followed by 5 weeks of control chow (CH). During the initial 10 weeks (weeks 1-10) the HF fed male rats had an increased rate of weight gain and feeding efficiency (FE) in comparison to CH-fed controls. In the female HF-fed rats, the FE was higher during weeks 1-5 than that seen in CH-fed females. The male HF-fed rats had significantly higher levels of FE than the female HF-fed rats during the first 10 week period. At the end of the tenth week, the HF-fed rats weighed significantly more than CH-fed controls. HF-fed male rats gained more weight than HF-fed female rats. During the 5 week period (weeks 11-16) of CH feeding, the body weight of the HF-fed rats was reduced. At the end of week 16 there was no difference between the body weights of the CH and HF fed rats. During the second cycle of HF feeding (weeks 16-25) the HF-diet further increased body weight gain in both male and female rats compared with CH-fed controls. There was no reduction in FE in HF-fed male and female rats during this period when compared to the first ten week HF feeding period. After the last 5 week period (weeks 26-30) of CH feeding, the formerly HF-fed rats had similar body weights as the control rats, but still had more body fat than control rats.(ABSTRACT TRUNCATED AT 250 WORDS)