Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction.

PubMed

Bender, Shawn B; DeMarco, Vincent G; Padilla, Jaume; Jenkins, Nathan T; Habibi, Javad; Garro, Mona; Pulakat, Lakshmi; Aroor, Annayya R; Jaffe, Iris Z; Sowers, James R

2015-05-01

Patients with obesity and diabetes mellitus exhibit a high prevalence of cardiac diastolic dysfunction (DD), an independent predictor of cardiovascular events for which no evidence-based treatment exists. In light of renin-angiotensin-aldosterone system activation in obesity and the cardioprotective action of mineralocorticoid receptor (MR) antagonists in systolic heart failure, we examined the hypothesis that MR blockade with a blood pressure-independent low-dose spironolactone (LSp) would treat obesity-associated DD in the Zucker obese (ZO) rat. Treatment of ZO rats exhibiting established DD with LSp normalized cardiac diastolic function, assessed by echocardiography. This was associated with reduced cardiac fibrosis, but not reduced hypertrophy, and restoration of endothelium-dependent vasodilation of isolated coronary arterioles via a nitric oxide-independent mechanism. Further mechanistic studies revealed that LSp reduced cardiac oxidative stress and improved endothelial insulin signaling, with no change in arteriolar stiffness. Infusion of Sprague-Dawley rats with the MR agonist aldosterone reproduced the DD noted in ZO rats. In addition, improved cardiac function in ZO-LSp rats was associated with attenuated systemic and adipose inflammation and an anti-inflammatory shift in cardiac immune cell mRNAs. Specifically, LSp increased cardiac markers of alternatively activated macrophages and regulatory T cells. ZO-LSp rats had unchanged blood pressure, serum potassium, systemic insulin sensitivity, or obesity-associated kidney injury, assessed by proteinuria. Taken together, these data demonstrate that MR antagonism effectively treats established obesity-related DD via blood pressure-independent mechanisms. These findings help identify a particular population with DD that might benefit from MR antagonist therapy, specifically patients with obesity and insulin resistance. © 2015 American Heart Association, Inc.

Acute effect of the dual angiotensin-converting enzyme and neutral endopeptidase 24-11 inhibitor mixanpril on insulin sensitivity in obese Zucker rat

PubMed Central

Arbin, V; Claperon, N; Fournié-Zaluski, M -C; Roques, B P; Peyroux, J

2001-01-01

The aim of this study was to determine whether acute dual angiotensin-converting enzyme (ACE)/neutral endopeptidase 24-11 (NEP) inhibition could improve whole body insulin-mediated glucose disposal (IMGD) more than ACE inhibition alone and whether this effect was mediated by the kinin-nitric oxide (NO) pathway activation.We therefore compared in anaesthetized obese (fa/fa) Zucker rats (ZOs) the effects of captopril (2 mg kg−1, i.v.+2 mg kg−1 h−1), retrothiorphan (25 mg kg−1, i.v. +25 mg  kg−1 h−1), a selective NEP inhibitor, and mixanpril (25 mg kg−1, i.v.+25 mg kg−1 h−1), a dual ACE/NEP inhibitor, on IMGD using hyperinsulinaemic euglycaemic clamp technique. The role of the kinin-NO pathway in the effects of mixanpril was tested using a bradykinin B2 receptor antagonist (Hoe-140, 300 μg kg−1) and a NO-synthase inhibitor (Nω-nitro-L-arginine methyl ester, L-NAME, 10 mg kg−1 i.v. +10 mg kg−1 h−1) as pretreatments.Insulin sensitivity index (ISI) was lower in ZO controls than in lean littermates. Increases in ISI were observed in captopril- and retrothiorphan-treated ZOs. In mixanpril-treated ZOs, ISI was further increased, compared to captopril- and retrothiorphan-treated ZOs.In ZOs, Hoe-140 and L-NAME alone did not significantly alter and slightly reduced the ISI respectively. Hoe-140 and L-NAME markedly inhibited the ISI improvement induced by mixanpril.These results show that in obese insulin-resistant Zucker rats, under acute conditions, NEP or ACE inhibition can improve IMGD and that dual ACE/NEP inhibition improves IMGD more effectively than does either single inhibition. This effect is linked to an increased activation of the kinin-NO pathway. PMID:11399666

Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats.

PubMed

McCune, S A; Durant, P J; Jenkins, P A; Harris, R A

1981-12-01

Hepatocytes isolated from genetically obese female Zucker rats and lean female Zucker rats were compared. Hepatocytes from fed obese rats exhibited greater rates of fatty acid synthesis, more extensive accumulation of lactate and pyruvate from their glycogen stores, increased rates of net glucose utilization but produced less ketone bodies from exogenous fatty acids and had lower citrate levels than hepatocytes from lean rats. Lipogenesis was not as sensitive to dibutyryl cyclic AMP (DBcAMP) inhibition in hepatocytes from obese rats but glycogenolysis was stimulated to the same extent by this nucleotide in both preparations. Ketogenesis was less sensitive to stimulation by DBcAMP in hepatocytes from obese rats. A difference in sensitivity of lipogenesis to DBcAMP was not found when lactate plus pyruvate was added to the incubation medium, suggesting that a greater rate of glycolysis by hepatocytes from obese rats accounts for their relative insensitivity to DBcAMP. Citrate levels were elevated by DBcAMP to a greater extent in hepatocytes from obese rats. Hepatocytes prepared from lean rats starved for 48 hr were glycogen depleted and lacked significant capacity for lipogenesis and glycogen synthesis. In contrast, hepatocytes isolated from starved obese rats retained considerable amounts of liver glycogen and exhibited detectable rates of lipogenesis and glycogen synthesis. Hepatocytes prepared from starved lean rats gave faster apparent rates of lactate gluconeogenesis than hepatocytes prepared from starved obese rats. Thus, hepatocytes prepared from obese Zucker rats are more glycogenic, glycolytic, and lipogenic but less ketogenic and glucogenic than hepatocytes prepared from lean rats.

Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats.

PubMed

Daubioul, Catherine; Rousseau, Nicolas; Demeure, Roger; Gallez, Bernard; Taper, Henryk; Declerck, Barbara; Delzenne, Nathalie

2002-05-01

This study was designed to compare the effects of dietary supplementation with nondigestible carbohydrates, differing in fermentability by colonic bacteria, on hepatic steatosis in growing obese Zucker rats. Male Zucker fa/fa rats were divided into three groups: a control group that received the basal diet, a fructan group that received 10 g highly fermented Synergy 1/100 g diet and a cellulose group that received 10 g poorly fermented Vivapur Microcrystalline cellulose/100 g diet. Rats consuming fructan had a lower energy intake, a lower body weight and less triacylglycerol accumulation in the liver as assessed in vivo by nuclear magnetic resonance (NMR) spectroscopy, and ex vivo by biochemical and histochemical analysis compared with the control and/or cellulose groups. The high fermentation of fructans compared with cellulose was reflected by greater cecal contents and by a twofold greater propionate concentration in the portal vein of rats fed fructan compared with those fed cellulose. By measuring the capacity of hepatocytes isolated from liver of Zucker rats to synthesize triglycerides or total lipids from different precursors, we showed that propionate, at the concentrations measured in the portal vein of rats treated with fructan, selectively decreased the incorporation of acetate into total lipids, a phenomenon that could contribute, along with the lower energy intake, to less triglyceride accumulation in the liver of obese Zucker rats fed dietary fructans.

α-Motoneurons maintain biophysical heterogeneity in obesity and diabetes in Zucker rats.

PubMed

MacDonell, Christopher W; Chopek, Jeremy W; Gardiner, Kalan R; Gardiner, Phillip F

2017-10-01

Small-diameter sensory dysfunction resulting from diabetes has received much attention in the literature, whereas the impact of diabetes on α-motoneurons (MN) has not. In addition, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker diabetic fatty (ZDF) rats were separated into lean, obese (ZDF fed standard chow), and diabetic (ZDF fed high-fat diet that led to diabetes) groups. Glass micropipettes recorded hindlimb MN properties from identified flexor and extensor MN. MN were separated within their groups on the basis of input conductance, which created high- and low-input conductance subpopulations for each. A significant shorter (20%) afterhyperpolarization half-decay (AHP 1/2 ) was found in low-conductance MN for the diabetic group only, whereas AHP½ tended to be shorter in the obese group (19%). Significant positive correlations were found among rheobase and input conductance for both lean and obese animals. No differences were found between the groups for afterhyperpolarization amplitude (AHP amp ), input conductance, rheobase, or any of the rhythmic firing properties (frequency-current slope and spike-frequency adaptation index). MN properties continue to be heterogeneous in obese and diabetic animals. Obesity does not seem to influence lumbar MN. Despite the resistance of MN to the impact of diabetes, the reduced AHP 1/2 decay and the tendency for a reduction in AHP amp may be the first sign of change to MN function. NEW & NOTEWORTHY Knowledge about the impact of obesity and diabetes on the biophysical properties of motoneurons is lacking. We found that diabetes reduces the duration of the afterhyperpolarization and that motoneuron function is unchanged by obesity. A reduced afterhyperpolarization may impact discharge characteristics and may be the first sign of change to motoneuron function. Copyright �

Effects of Alpha-Lipoic Acid on Oxidative Stress and Kinin Receptor Expression in Obese Zucker Diabetic Fatty Rats.

PubMed

Midaoui, Adil El; Talbot, Sébastien; Lahjouji, Karim; Dias, Jenny Pena; Fantus, I George; Couture, Réjean

2015-06-01

To investigate the impact of alpha-lipoic acid on superoxide anion production and NADPH oxidase activity as well as on the expression of kinin B1 and B2 receptors in key organs of obese Zucker Diabetic Fatty rats. Superoxide anion production was measured by lucigenin chemiluminescence. Kinin B1 and B2 receptors expression was measured at protein and mRNA levels by western blot and qRT-PCR in key organs of Zucker Diabetic Fatty and Zucker lean control rats treated for a period of 6 weeks with a standard diet or a diet containing the antioxidant α-lipoic acid (1 g/kg). Superoxide anion production and NADPH oxidase activity were significantly enhanced in aorta and adipose tissue of Zucker Diabetic Fatty rats. Kinin B1 and B2 receptors expression levels were also significantly increased in the liver and the gastrocnemius muscle of Zucker Diabetic Fatty rats. Expression of both receptors was not altered in the pancreas of Zucker Diabetic Fatty rats and was undetectable in white retroperitoneal adipose tissue. Alpha-lipoic acid prevented the rise in NADPH oxidase activity in aorta and epididymal adipose tissue of Zucker Diabetic Fatty rats and the upregulation of kinin B1 receptor in liver and gastrocnemius muscle and that of kinin B2 receptor in the liver. Alpha-lipoic acid treatment was found to prevent the final body weight increase without affecting significantly hyperglycemia, hyperinsulinemia and insulin resistance index in Zucker Diabetic Fatty rats. Findings support the hypothesis that oxidative stress is implicated in the induction of kinin B1 receptor in Zucker Diabetic Fatty rats. The ability of α-lipoic acid to blunt the body weight gain appears to be mediated in part by preventing NADPH oxidase activity rise in adipose tissue and reversing the hepatic upregulation of kinin B1 receptor in Zucker Diabetic Fatty rats.

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats.

PubMed

Tenorio, Neuli M; Ribeiro, Daniel A; Alvarenga, Tathiana A; Fracalossi, Ana Carolina C; Carlin, Viviane; Hirotsu, Camila; Tufik, Sergio; Andersen, Monica L

2013-01-01

The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.

Cereal based diets modulate some markers of oxidative stress and inflammation in lean and obese Zucker rats

PubMed Central

2011-01-01

Background The potential of cereals with high antioxidant capacity for reducing oxidative stress and inflammation in obesity is unknown. This study investigated the impact of wheat bran, barley or a control diet (α-cellulose) on the development of oxidative stress and inflammation in lean and obese Zucker rats. Methods Seven wk old, lean and obese male Zucker rats (n = 8/group) were fed diets that contained wheat bran, barley or α-cellulose (control). After 3 months on these diets, systolic blood pressure was measured and plasma was analysed for glucose, insulin, lipids, oxygen radical absorbance capacity (ORAC), malondialdehyde, glutathione peroxidase and adipokine concentration (leptin, adiponectin, interleukin (IL)-1β, IL-6, TNFα, plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1). Adipokine secretion rates from visceral and subcutaneous adipose tissue explants were also determined. Results Obese rats had higher body weight, systolic blood pressure and fasting blood lipids, glucose, insulin, leptin and IL-1β in comparison to lean rats, and these measures were not reduced by consumption of wheat bran or barley based diets. Serum ORAC tended to be higher in obese rats fed wheat bran and barley in comparison to control (p = 0.06). Obese rats had higher plasma malondialdehyde (p < 0.01) and lower plasma glutathione peroxidase concentration (p < 0.01) but these levels were not affected by diet type. PAI-1 was elevated in the plasma of obese rats, and the wheat bran diet in comparison to the control group reduced PAI-1 to levels seen in the lean rats (p < 0.05). These changes in circulating PAI-1 levels could not be explained by PAI-1 secretion rates from visceral or subcutaneous adipose tissue. Conclusions A 3-month dietary intervention was sufficient for Zucker obese rats to develop oxidative stress and systemic inflammation. Cereal-based diets with moderate and high antioxidant capacity elicited modest improvements in indices of

Expression of fourteen novel obesity-related genes in Zucker diabetic fatty rats.

PubMed

Schmid, Peter M; Heid, Iris; Buechler, Christa; Steege, Andreas; Resch, Markus; Birner, Christoph; Endemann, Dierk H; Riegger, Guenter A; Luchner, Andreas

2012-07-13

Genome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity. A multitude of new loci has recently been reported, but the exact function of most of the according genes is not known. The aim of our study was to start elucidating the function of some of these genes. We performed an expression analysis of fourteen genes, namely BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MCR4, MTCH2, NEGR1, NRXN3, TMEM18, SEC16B and TFAP2B, via real-time RT-PCR in adipose tissue of the kidney capsule, the mesenterium and subcutaneum as well as the hypothalamus of obese Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats at an age of 22 weeks. All of our target genes except for SEC16B showed the highest expression in the hypothalamus. This suggests a critical role of these obesity-related genes in the central regulation of energy balance. Interestingly, the expression pattern in the hypothalamus showed no differences between obese ZDF and lean ZL rats. However, LYPLAL1, TFAP2B, SEC16B and FAIM2 were significantly lower expressed in the kidney fat of ZDF than ZL rats. NEGR1 was even lower expressed in subcutaneous and mesenterial fat, while MTCH2 was higher expressed in the subcutaneous and mesenterial fat of ZDF rats. The expression pattern of the investigated obesity genes implies for most of them a role in the central regulation of energy balance, but for some also a role in the adipose tissue itself. For the development of the ZDF phenotype peripheral rather than central mechanisms of the investigated genes seem to be relevant.

Rimonabant reduces the essential value of food in the genetically obese Zucker rat: an exponential demand analysis.

PubMed

Rasmussen, Erin B; Reilly, William; Buckley, Jessica; Boomhower, Steven R

2012-02-01

Research on free-food intake suggests that cannabinoids are implicated in the regulation of feeding. Few studies, however, have characterized how environmental factors that affect food procurement interact with cannabinoid drugs that reduce food intake. Demand analysis provides a framework to understand how cannabinoid blockers, such as rimonabant, interact with effort in reducing demand for food. The present study examined the effects rimonabant had on demand for sucrose in obese Zucker rats when effort to obtain food varied and characterized the data using the exponential ("essential value") model of demand. Twenty-nine male (15 lean, 14 obese) Zucker rats lever-pressed under eight fixed ratio (FR) schedules of sucrose reinforcement, in which the number of lever-presses to gain access to a single sucrose pellet varied between 1 and 300. After behavior stabilized under each FR schedule, acute doses of rimonabant (1-10mg/kg) were administered prior to some sessions. The number of food reinforcers and responses in each condition was averaged and the exponential and linear demand equations were fit to the data. These demand equations quantify the value of a reinforcer by its sensitivity to price (FR) increases. Under vehicle conditions, obese Zucker rats consumed more sucrose pellets than leans at smaller fixed ratios; however, they were equally sensitive to price increases with both models of demand. Rimonabant dose-dependently reduced reinforcers and responses for lean and obese rats across all FR schedules. Data from the exponential analysis suggest that rimonabant dose-dependently increased elasticity, i.e., reduced the essential value of sucrose, a finding that is consistent with graphical depictions of normalized demand curves. Copyright © 2011 Elsevier Inc. All rights reserved.

Renal protection by a soy diet in obese Zucker rats is associated with restoration of nitric oxide generation.

PubMed

Trujillo, Joyce; Ramírez, Victoria; Pérez, Jazmín; Torre-Villalvazo, Ivan; Torres, Nimbe; Tovar, Armando R; Muñoz, Rosa M; Uribe, Norma; Gamba, Gerardo; Bobadilla, Norma A

2005-01-01

The obese Zucker rat is a valuable model for studying kidney disease associated with obesity and diabetes. Previous studies have shown that substitution of animal protein with soy ameliorates the progression of renal disease. To explore the participation of nitric oxide (NO) and caveolin-1 in this protective effect, we evaluated proteinuria, creatinine clearance, renal structural lesions, nitrites and nitrates urinary excretion (UNO(2)(-)/NO(3)V), and mRNA and protein levels of neuronal NO synthase (nNOS), endothelial NOS (eNOS), and caveolin-1 in lean and fatty Zucker rats fed with 20% casein or soy protein diet. After 160 days of feeding with casein, fatty Zucker rats developed renal insufficiency, progressive proteinuria, and renal structural lesions; these alterations were associated with an important fall of UNO(2)(-)/NO(3)V, changes in nNOS and eNOS mRNA levels, together with increased amount of eNOS and caveolin-1 present in plasma membrane proteins of the kidney. In fatty Zucker rats fed with soy, we observed that soy diet improved renal function, UNO(2)(-)/NO(3)V, and proteinuria and reduced glomerulosclerosis, tubular dilation, intersticial fibrosis, and extracapilar proliferation. Renal protection was associated with reduction of caveolin-1 and eNOS in renal plasma membrane proteins. In conclusion, our results suggest that renal protective effect of soy protein appears to be mediated by improvement of NO generation and pointed out to caveolin-1 overexpression as a potential pathophysiological mechanism in renal disease.

Effect of obese and lean Zucker rat sera on human and rat prostate cancer cells: implications in obesity-related prostate tumor biology.

PubMed

Lamarre, Neil S; Ruggieri, Michael R; Braverman, Alan S; Gerstein, Matthew I; Mydlo, Jack H

2007-01-01

Several reports have demonstrated the effects of obesity on prostate cancer. Also several reports have linked expression of vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (FGF-2) to prostate cancer aggressiveness. The objective of this study was to determine whether a difference exists between lean and obese Zucker rat sera on proliferation prostate cancer cell lines, as well as to examine the differences in FGF-2 and VEGF concentrations. Ten-week-old female obese and lean Zucker rat sera were subjected to charcoal stripping and tested for the proliferation of human LNCaP and rat AT3B-1 prostate cancer cells. An acetonitrile extract of the charcoal used to strip the sera was also tested for mitogenicity. VEGF and FGF-2 concentrations were determined by enzyme-linked immunosorbent assay. Both unstripped and charcoal-stripped obese rat sera had a greater mitogenic effect than did the lean sera on the LNCaP cell line. Charcoal stripping of both obese and lean sera reduced the mitogenic effect on the AT3B-1 cell line. The acetonitrile extract of the charcoal used to strip the sera was unable to recover this proliferative effect. The concentration of VEGF was greater in the obese serum than in the lean serum, and charcoal stripping reduced the concentrations of both FGF-2 and VEGF. The finding of greater VEGF in obese rat sera, as well as greater mitogenic responses on human prostate cancer cells in vitro, suggests this as one of the many possible mechanisms involved in obesity-related prostate cancer biology.

Effects of clenbuterol on insulin resistance in conscious obese Zucker rats.

PubMed

Pan, S J; Hancock, J; Ding, Z; Fogt, D; Lee, M; Ivy, J L

2001-04-01

The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.

Effects of 2 G on adiposity, leptin, lipoprotein lipase, and uncoupling protein-1 in lean and obese Zucker rats

NASA Technical Reports Server (NTRS)

Warren, L. E.; Horwitz, B. A.; Hamilton, J. S.; Fuller, C. A.

2001-01-01

Male Zucker rats were exposed to 2 G for 8 wk to test the hypothesis that the leptin regulatory pathway contributes to recovery from effects of 2 G on feeding, growth, and nutrient partitioning. After initial hypophagia, body mass-independent food intake of the lean rats exposed to 2 G surpassed that of the lean rats maintained at 1 G, but food intake of the obese rats exposed to 2 G remained low. After 8 wk at 2 G, body mass and carcass fat were less in both genotypes. Leptin and percent fat were lower in lean rats exposed to 2 G vs. 1 G but did not differ in obese rats exposed to 2 G vs. 1 G. Although exposure to 2 G did not alter uncoupling protein-1 levels, it did elicit white fat pad-specific changes in lipoprotein lipase activity in obese but not lean rats. We conclude that 2 G affects both genotypes but that the lean Zucker rats recover their food intake and growth rate and retain "normal" lipoprotein lipase activity to a greater degree than do the obese rats, emphasizing the importance of a functional leptin regulatory pathway in this acclimation.

Anti-Obesity Effects of Onion Extract in Zucker Diabetic Fatty Rats

PubMed Central

Yoshinari, Orie; Shiojima, Yoshiaki; Igarashi, Kiharu

2012-01-01

Anti-obesity effects of onion extract were determined in obesity and diabetes-prone Zucker diabetic fatty rats by measuring the efficacy of markers concerned with diabetes and obesity. Body and adipose tissue weights in 5% of onion extract-fed group were found to be significantly lower than the control group without onion extract. Fasting blood glucose and HOMA-IR levels were also improved, although the serum insulin and leptin levels did not show any remarkable difference. Serum triglyceride and free fatty acid levels in both the 3% and 5%-fed group were found to be reduced compared to the control group. Additionally the feeding of the onion extract increased the glucose tolerance. These results suggest that dietary onion extract is beneficial for improving diabetes by decreasing lipid levels. We also examined differentiation ability of rat white preadipocyte cells using the onion extract and its sulfur-containing components. Cycloalliin, S-methyl-L-cysteine, S-propyl-L-cysteine sulfoxide, dimethyl trisulfide, especially S-methyl-L-cysteine sulfoxide were reported to be effective in inhibiting formation of oil drop in the cells, suggesting that these compounds may be involved in the anti-obesity effect of the onion extract. PMID:23201769

Microvascular disorders in obese Zucker rats are restored by a rice bran diet.

PubMed

Justo, M L; Claro, C; Vila, E; Herrera, M D; Rodriguez-Rodriguez, R

2014-05-01

Nutritional-based approaches aimed to prevent microvascular dysfunction associated to obesity present potential advantages over pharmacological strategies. Our aim was to test whether a rice bran enzymatic extract (RBEE)-supplemented diet could attenuate microvascular alterations in obese rats. Lean and obese Zucker rats were fed standard diet supplemented or not with 1% and 5% RBEE for 20 weeks. Functional studies were performed in small mesenteric arteries in isometric myograph. Immunoblotting and fluorescence studies were made in arterial homogenates and arterial sections, respectively. RBEE-supplementation restored microvascular function in obese rats through a marked increase in NO and endothelial-derived hyperpolarizing factor contribution by up-regulation of eNOS and calcium-activated potassium channels expression, respectively, in association to a substantial reduction of microvascular inflammation and superoxide anion formation. These data agrees with the beneficial actions of RBEE on dyslipidemia, hyperinsulinemia and hypertension in obesity. The multi-factorial properties of RBEE-diet, especially for restoring the function of small resistance arteries shows this dietary-based approach to be a promising candidate for prevention of microvascular alterations in obesity, which are crucial in cardiovascular events in obese subjects. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulation of palmitoyl-CoA chain elongation by clofibric acid in the liver of Zucker fa/fa rats.

PubMed

Toyama, Tomoaki; Kudo, Naomi; Mitsumoto, Atsushi; Kawashima, Yoichi

2005-05-01

The regulation of palmitoyl-CoA chain elongation (PCE) by clofibric acid [2-(4-chlorophenoxy)-2-methylpropionic acid] was investigated in comparison with stearoyl-CoA desaturase (SCD) in the liver of obese Zucker fa/fa rats. The proportion of oleic acid in the hepatic lipids of Zucker obese rats is 2.7 times higher than that of lean littermates. The activities of PCE and SCD in the liver of Zucker obese rats were markedly higher than in lean rats, and the hepatic uptake of 2-deoxyglucose (2-DG) was also higher in Zucker obese rats compared with lean rats. The increased activities of SCD and PCE in Zucker obese rats were due to the enhanced expression of mRNA of both SCD1 and rat FA elongase 2 (rELO2), but not SCD2 or rELO1. The proportion of oleic acid in the liver was significantly increased by the administration of clofibric acid to Zucker obese rats, and the hepatic PCE activity and rELO2 mRNA expression, but not the SCD activity or SCD1 mRNA expression, were increased in response to clofibric acid treatment. By contrast, the activities of both PCE and SCD and the mRNA expression of SCD1 and rELO2 in the liver were increased by the treatment of Zucker lean rats with clofibric acid. Multiple regression analysis, which was performed to determine the relationships involving PCE activity, SCD activity, and the proportion of oleic acid, revealed that the three parameters were significantly correlated and that the standardized partial regression coefficient of PCE was higher than that of SCD. These results indicate that oleic acid is synthesized by the concerted action of PCE and SCD and that PCE plays a crucial role in the formation of oleic acid when Zucker fa/fa rats are given clofibric acid.

Effect of lateral hypothalamic lesion on brown adipose tissue of Zucker lean and obese rats.

PubMed

Holt, S J; York, D A

1988-01-01

Acute (10-day) lateral hypothalamic (LH) lesion induced a reduction of food intake in both lean and obese Zucker rats which averaged about 50% over the course of the first 10 days. The aphagia associated with a fall in body weight in both genotypes which was greater than their respective pair-fed controls, indicating a change in energetic efficiency. The reduced level of BAT protein, mitochondria and GDP binding observed in the obese rat was restored after LH lesion, suggesting the reestablishment of a normal sympathetic drive to the tissue. The markedly lower plasma insulin concentration in the LH lesioned obese rat is consistent with a reduction in parasympathetic activity in these animals. Food restriction in the sham lean rat reduced BAT protein content and mitochondrial GDP binding, whereas no such changes were observed in the food restricted obese rat. This demonstrates the insensitivity of the obese rat to dietary signals and may imply that LH lesion restores diet-induced BAT thermogenesis in the obese rat.

A casein diet added isoflavone-enriched soy protein favorably affects biomarkers of steatohepatitis in obese Zucker rats.

PubMed

Gudbrandsen, Oddrun Anita; Wergedahl, Hege; Berge, Rolf Kristian

2009-05-01

Dietary supplementation of a soy protein enriched with isoflavones (HDI) has been shown to improve fatty liver in obese rats. The main objective of this study was to investigate whether HDI would influence the inflammatory status in livers of obese rats with fatty liver. Male obese Zucker fa/fa rats were fed casein (controls) or casein supplemented with HDI (containing 4.00 g of genistein and 4.50 g of daidzein per kilogram of diet) for 6 wk. The HDI-fed rats had a markedly lower hepatic concentration of triacylglycerol when compared with controls. The decreased aspartate transaminase/alanine transaminase ratio in plasma, together with lower circulating levels of alkaline phosphatase and bile acids after HDI feeding, implied an improved hepatitis. This was supported by decreased plasma and hepatic mRNA levels of tumor necrosis factor-alpha, lower plasma levels of interleukin-1beta and monocyte chemoattractant protein-1, and an increased anti-inflammatory fatty acid index in plasma. HDI also seemed to protect the rats from oxidative damage, because the level of lipid peroxides in triacylglycerol-rich lipoproteins after in vitro copper oxidation was lower for HDI-fed rats when compared with controls. These results show that isoflavone-enriched soy protein favorably affects biomarkers of hepatic inflammation in obese Zucker fa/fa rats with fatty liver. Thus, dietary soy proteins enriched in isoflavones may be a promising agent to improve steatohepatitis in patients.

Implications of obesity for tendon structure, ultrastructure and biochemistry: a study on Zucker rats.

PubMed

Biancalana, Adriano; Velloso, Lício Augusto; Taboga, Sebastião Roberto; Gomes, Laurecir

2012-02-01

The extracellular matrix consists of collagen, proteoglycans and non-collagen proteins. The incidence of obesity and associated diseases is currently increasing in developed countries. Obesity is considered to be a disease of modern times, and genes predisposing to the disease have been identified in humans and animals. The objective of the present study was to compare the morphological and biochemical aspects of the deep digital flexor tendon of lean (Fa/Fa or Fa/fa) and genetically obese (fa/fa) Zucker rats. Ultrastructural analysis showed the presence of lipid droplets in both groups, whereas disorganized collagen fibril bundles were observed in obese animals. Lean animals presented a larger amount of non-collagen proteins and glycosaminoglycans than obese rats. We propose that the overweight and lesser physical activity in obese animals may have provoked the alterations in the composition and organization of extracellular matrix components but a genetic mechanism cannot be excluded. These alterations might be related to organizational and structural modifications in the collagen bundles that influence the mechanical properties of tendons and the progression to a pathological state. Copyright © 2011 Elsevier Ltd. All rights reserved.

Age-related decrease in sensitivity to glucagon and dibutyryl cyclic AMP inhibition of fatty acid synthesis in hepatocytes isolated from obese female Zucker rats.

PubMed

McCune, S A; Durant, P J; Harris, R A

1984-02-01

Hepatocytes were isolated from 3 and 5 month old female genetically obese Zucker rats and their lean littermate controls. An age-dependent loss in sensitivity of fatty acid synthesis to inhibition by both glucagon and dibutyryl cyclic AMP was observed with hepatocytes from the obese rats. Hepatocytes from lean animals were much more sensitive to these agents, regardless of age. Low concentrations of glucagon and dibutyryl cyclic AMP actually produced some stimulation of fatty acid synthesis with hepatocytes prepared from the older obese rats. 5-Tetradecyloxy-2-furoic acid, a compound which inhibits fatty acid synthesis, was a very effective inhibitor of fatty acid synthesis by hepatocytes isolated from all rats used in the study. An inhibition of lactate plus pyruvate accumulation and a strong stimulation of glycogenolysis occurred in response to both glucagon and dibutyryl cyclic AMP with hepatocytes from both age groups of lean and obese rats. The results suggest that with aging of the obese female Zucker rat some step of hepatic fatty acid synthesis becomes progressively less sensitive to inhibition by glucagon and dibutyryl cyclic AMP. This may play an important role in maintenance of obesity in these animals.

Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

NASA Technical Reports Server (NTRS)

Brooks-Asplund, Esther M.; Shoukas, Artin A.; Kim, Soon-Yul; Burke, Sean A.; Berkowitz, Dan E.

2002-01-01

We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.

Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats.

PubMed

Morán-Ramos, Sofía; Avila-Nava, Azalia; Tovar, Armando R; Pedraza-Chaverri, José; López-Romero, Patricia; Torres, Nimbe

2012-11-01

Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats.

Effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 on hepatic steatosis in Zucker rats.

PubMed

Plaza-Diaz, Julio; Gomez-Llorente, Carolina; Abadia-Molina, Francisco; Saez-Lara, Maria Jose; Campaña-Martin, Laura; Muñoz-Quezada, Sergio; Romero, Fernando; Gil, Angel; Fontana, Luis

2014-01-01

We have previously described the safety and immunomodulatory effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 in healthy volunteers. The scope of this work was to evaluate the effects of these probiotic strains on the hepatic steatosis of obese rats. We used the Zucker rat as a genetic model of obesity. Zucker-Lepr(fa/fa) rats received one of three probiotic strains, a mixture of L. paracasei CNCM I-4034 and B. breve CNCM I-4035, or a placebo for 30 days. An additional group of Zucker-lean+/fa rats received a placebo for 30 days. No alterations in intestinal histology, in the epithelial, lamina propria, muscular layers of the ileal or colonic mucosa, or the submucosae, were observed in any of the experimental groups. Triacylglycerol content decreased in the liver of Zucker-Lepr(fa/fa) rats that were fed L. rhamnosus, B. breve, or the mixture of B. breve and L. paracasei. Likewise, the area corresponding to neutral lipids was significantly smaller in the liver of all four groups of Zucker-Lepr(fa/fa) rats that received probiotics than in rats fed the placebo. Zucker-Lepr(fa/fa) rats exhibited significantly greater serum LPS levels than Zucker-lean+/fa rats upon administration of placebo for 30 days. In contrast, all four groups of obese Zucker-Lepr(fa/fa) rats that received LAB strains exhibited serum LPS concentrations similar to those of Zucker-lean+/fa rats. Serum TNF-α levels decreased in the Zucker-Lepr(fa/fa) rats that received B. breve, L. rhamnosus, or the mixture, whereas L. paracasei feeding decreased IL-6 levels in the serum of Zucker-Lepr(fa/fa) rats. In conclusion, the probiotic strains reduced hepatic steatosis in part by lowering serum LPS, and had an anti-inflammatory effect in obese Zucker rats.

COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats.

PubMed

Muñoz, Mercedes; Sánchez, Ana; Pilar Martínez, María; Benedito, Sara; López-Oliva, Maria-Elvira; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

2015-07-01

Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS. Copyright © 2015 Elsevier Inc. All rights reserved.

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats.

PubMed

Frisbee, Jefferson C

2003-07-01

Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand.

Deposition of dietary fatty acids in young Zucker rats fed a cafeteria diet.

PubMed

Rafecas, I; Esteve, M; Fernández-López, J A; Remesar, X; Alemany, M

1992-10-01

The content and accretion of fatty acids in 30, 45 and 60-day-old Zucker lean Fa/? and obese fa/fa rats fed either reference chow or a cafeteria diet has been studied, together with their actual fatty acid intake during each period. Diet had little overall effect on the pattern of deposition of fatty acids, but quantitatively the deposition of fat was much higher in cafeteria-fed rats. The fat-rich cafeteria diet allowed the direct incorporation of most fatty acids into the rat lipids, whilst chow feeding activated lipogenesis and the deposition of a shorter chain and more saturated pattern of fatty acids. Genetic, obesity induced a significant expansion of net lipogenesis when compared with lean controls. Cafeteria-fed obese rats accrued a high proportion of fatty acids, which was close to that ingested, but nevertheless showed a net de novo synthesis of fatty acids. It is postulated that the combined effects of genetic obesity and a fat-rich diet result in high rates of fat accretion with limited net lipogenesis. Lean Zucker rats show a progressive impairment of their delta 5-desaturase system, a situation also observed in obese rats fed a reference diet. In Zucker obese rats, cafeteria feeding resulted in an alteration of the conversion of C18:2 into C20:3. The cafeteria diet fully compensated for these drawbacks by supplying very high amounts of polyunsaturated fatty acids.

Renoprotective mechanisms of soy protein intake in the obese Zucker rat

PubMed Central

Trujillo, Joyce; Cruz, Cristino; Tovar, Armando; Vaidya, Vishal; Zambrano, Elena; Bonventre, Joseph V.; Gamba, Gerardo; Torres, Nimbe; Bobadilla, Norma A.

2008-01-01

We previously showed that long-term consumption of a soy protein diet (SoyP) reduces renal damage in obese Zucker (ObeseZ) rats by restoring urinary NO2 and NO3 excretion (UNO2/NO3V), suggesting that nitric oxide (NO) deficiency may contribute to the renal progression observed in this model. In addition, there is compelling evidence that hyperleptinemia produced deleterious effects on the kidney through its interaction with the short leptin receptor (ObRa). This study was designed to evaluate the contribution of the NO/endothelial NO synthase (eNOS) system, renal oxidative stress, and ObRa expression to the renoprotection conferred by the consumption of a SoyP in ObeseZ rats. Ten lean and ten male ObeseZ rats were included. One-half of each group was fed with a 20% SoyP and the other half with a 20% casein protein diet (CasP) over the course of 160 days. eNOS protein levels and phosphorylation, renal lipoperoxidation (rLPO), and antioxidant enzyme activity were assessed. In addition, renal ObRa, TGF-β, and kidney injury molecule (Kim-1) mRNA levels, as well as urinary Kim-1 levels, were measured. Renal injury observed in ObeseZ rats fed with CasP was not associated with changes in eNOS expression or phosphorylation. However, this group did present with increased rLPO, reduced catalase activity, and upregulation of ObRa, TGF-β1, and Kim-1. In contrast, ObeseZ rats fed with a SoyP exhibited a reduction in NOS-Thr495 phosphorylation and rLPO, as well as an enhanced catalase activity. These findings were associated with a significant reduction of ObRa, TGF-β1, and Kim-1 mRNA levels and urinary Kim-1 protein. Our results show that renoprotection by SoyP in ObeseZ rats is in part mediated by increased NO availability secondary to a reduction in eNOS-T495 phosphorylation and oxidative stress, together with a significant reduction in ObRa and TGF-β expression. PMID:18815216

Soy protein isolate modified metabolic phenotype and hepatic Wnt signaling in obese Zucker rats.

PubMed

Cain, J; Banz, W J; Butteiger, D; Davis, J E

2011-10-01

We have previously shown that soy protein isolate (SPI) with intact phytoestrogen content prevented obesity-related dysfunction. Recent data have suggested that soy ingredients may act as regulators of adipogenic programming in adipose tissue (AT) and liver. Thus, the current study was undertaken to determine whether the beneficial effects of SPI are linked to changes in adipogenic regulators, such as the Wnt signaling cascade. For this, lean (LZR) and obese Zucker (OZR) rats were provided isocaloric and isonitrogenous diets containing SPI, sodium caseinate, or dairy whey protein for 17 weeks. At termination, SPI increased body weight and total adiposity in rodents, which corresponded with an increase in both adipocyte size and number. Furthermore, markers of inflammation, hypercholesterolemia, and hepatic steatosis were all reduced in OZR rats provided SPI. Transcript abundance of several canonical and noncanonical Wnt signaling intermediates in liver, but not AT, was distinctly modified by SPI. Collectively, these data confirm the protective SPI attenuated obesity-related metabolic dysfunction conceivably through regulation of adipogenic programming, as evident by changes in AT morphology and hepatic Wnt signaling. Collectively, this study confirmed the potential utilization of soy protein and its bioactive ingredients for prevention and treatment of obesity-related comorbidities. © Georg Thieme Verlag KG Stuttgart · New York.

Joint feedback analysis modeling of nonesterified fatty acids in obese Zucker rats and normal Sprague-Dawley rats after different routes of administration of nicotinic acid.

PubMed

Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

2014-08-01

Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague-Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague-Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration-response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the "degree of disease" can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effect of a soluble cocoa fiber-enriched diet in Zucker fatty rats.

PubMed

Sánchez, David; Moulay, Leila; Muguerza, Begoña; Quiñones, Mar; Miguel, Marta; Aleixandre, Amaya

2010-06-01

The effects of a soluble cocoa fiber (SCF) were studied in Zucker fatty rats. Two groups of Zucker fatty rats were fed the following diets: standard diet and 5% SCF-enriched diet. A group of Zucker lean rats fed the standard diet was used for results comparison with obese Zucker animals. Solid and liquid intakes, body weight, plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure were recorded weekly. At the end of the experimental period insulin was determined, and fat apparent digestibility (FAD) and insulin resistance were calculated. The Zucker fatty rats fed 5% SCF-enriched diet showed less weight gain and food intake than those fed the standard diet. The group fed the fiber-enriched diet showed lower values of the total cholesterol/high-density lipoprotein cholesterol ratio and triglyceride levels than the standard group. FAD was also lower in the fiber group. Both SBP and DBP were decreased. In addition, SCF reduced plasma glucose and insulin, and as a consequence the insulin resistance was also decreased. Our data demonstrate that SCF resulted in an improvement of the studied risk factors associated with cardiometabolic disorders.

Diets containing salmon fillet delay development of high blood pressure and hyperfusion damage in kidneys in obese Zucker fa/fa rats.

PubMed

Vikøren, Linn A; Drotningsvik, Aslaug; Mwakimonga, Angela; Leh, Sabine; Mellgren, Gunnar; Gudbrandsen, Oddrun A

2018-04-01

Hypertension is the leading risk factor for cardiovascular and chronic renal diseases, affecting more than 1 billion people. Fish intake is inversely correlated with the prevalence of hypertension in several, but not all, studies, and intake of fish oil and fish proteins has shown promising potential to delay development of high blood pressure in rats. The effects of baked and raw salmon fillet intake on blood pressure and renal function were investigated in obese Zucker fa/fa rats, which spontaneously develop hypertension with proteinuria and renal failure. Rats were fed diets containing baked or raw salmon fillet in an amount corresponding to 25% of total protein from salmon and 75% of protein from casein, or casein as the sole protein source (control group) for 4 weeks. Results show lower blood pressure and lower urine concentrations of albumin and cystatin C (relative to creatinine) in salmon diet groups when compared to control group. Morphological examinations revealed less prominent hyperfusion damage in podocytes from rats fed diets containing baked or raw salmon when compared to control rats. In conclusion, diets containing baked or raw salmon fillet delayed the development of hypertension and protected against podocyte damage in obese Zucker fa/fa rats. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

Joint Feedback Analysis Modeling of Nonesterified Fatty Acids in Obese Zucker Rats and Normal Sprague–Dawley Rats after Different Routes of Administration of Nicotinic Acid

PubMed Central

Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

2014-01-01

Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague–Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague–Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration–response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the “degree of disease” can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2571–2584, 2014 PMID:24986056

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats.

PubMed

Brooks, Steven D; DeVallance, Evan; d'Audiffret, Alexandre C; Frisbee, Stephanie J; Tabone, Lawrence E; Shrader, Carl D; Frisbee, Jefferson C; Chantler, Paul D

2015-12-01

The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7-8, 12-13, and 16-17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7-8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS. Copyright © 2015 the American Physiological Society.

Peroxisomal palmitoyl-CoA oxidation in the Zucker rat.

PubMed Central

Brady, P S; Hoppel, C L

1983-01-01

The effects of 3 or 6 days of starvation on hepatic peroxisomal palmitoyl-CoA oxidation were examined in adult lean and obese Zucker rats. When expressed either per mg of DNA or per total liver, obese rats had almost 2-fold higher oxidation rates than the lean rats. Within 6 days of starvation rates fell by 50% among both phenotypes. When data were expressed per 100 g body wt., lean and obese rats had similar rates, falling from a mean of 0.57 to 0.28 mumol/min per 100 g body wt. within 6 days of starvation. Peroxisomal oxidative changes paralleled mitochondrial beta-oxidative changes. PMID:6882399

Cingulin Contains Globular and Coiled-Coil Domains and Interacts with Zo-1, Zo-2, Zo-3, and Myosin

PubMed Central

Cordenonsi, Michelangelo; D'Atri, Fabio; Hammar, Eva; Parry, David A.D.; Kendrick-Jones, John; Shore, David; Citi, Sandra

1999-01-01

We characterized the sequence and protein interactions of cingulin, an M r 140–160-kD phosphoprotein localized on the cytoplasmic surface of epithelial tight junctions (TJ). The derived amino acid sequence of a full-length Xenopus laevis cingulin cDNA shows globular head (residues 1–439) and tail (1,326–1,368) domains and a central α-helical rod domain (440–1,325). Sequence analysis, electron microscopy, and pull-down assays indicate that the cingulin rod is responsible for the formation of coiled-coil parallel dimers, which can further aggregate through intermolecular interactions. Pull-down assays from epithelial, insect cell, and reticulocyte lysates show that an NH2-terminal fragment of cingulin (1–378) interacts in vitro with ZO-1 (K d ∼5 nM), ZO-2, ZO-3, myosin, and AF-6, but not with symplekin, and a COOH-terminal fragment (377–1,368) interacts with myosin and ZO-3. ZO-1 and ZO-2 immunoprecipitates contain cingulin, suggesting in vivo interactions. Full-length cingulin, but not NH2-terminal and COOH-terminal fragments, colocalizes with endogenous cingulin in transfected MDCK cells, indicating that sequences within both head and rod domains are required for TJ localization. We propose that cingulin is a functionally important component of TJ, linking the submembrane plaque domain of TJ to the actomyosin cytoskeleton. PMID:10613913

Cardiac β-adrenergic responsiveness of obese Zucker rats: The role of AMPK.

PubMed

Bussey, Carol T; Thaung, Hp Aye; Hughes, Gillian; Bahn, Andrew; Lamberts, Regis R

2018-06-05

What is the central question of the study? What is the main finding and its importance? 1. Is the reduced signalling of AMPK, a key regulator of energy homeostasis in the heart, responsible for the reduced β-adrenergic responsiveness of the heart in obesity? 2. Inhibition of AMPK in isolated hearts prevented the reduced cardiac β-adrenergic responsiveness of obese rats, which was accompanied by reduced phosphorylation of AMPK, a proxy of AMPK activity. This suggests a direct functional link between β-adrenergic responsiveness and AMPK signalling in the heart, and that AMPK might be an important target to restore the β-adrenergic responsiveness in the heart in obesity. The obesity epidemic impacts heavily on cardiovascular health, in part due to changes in cardiac metabolism. AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis in the heart, and is regulated by β-adrenoceptors (AR) under normal conditions. In obesity, chronic sympathetic overactivation leads to impaired cardiac β-AR responsiveness, although it is unclear whether AMPK signalling, downstream of β-AR, contributes to this dysfunction. Therefore, we aimed to determine whether reduced AMPK signalling is responsible for the reduced β-AR responsiveness in obesity. In isolated hearts of lean and obese Zucker rats, we tested β-AR responsiveness to β 1 -AR agonist isoproterenol (ISO, 1 × 10 -10 - 5 × 10 -8  M) in the absence and presence of the AMPK inhibitor compound C (CC, 10 μM). β 1 -AR expression and AMPK phosphorylation were assessed by Western blot. β-Adrenergic responsiveness was reduced in the hearts of obese rats (LogEC50 of ISO-developed pressure dose-response curves: lean -8.53 ± 0.13 vs. obese -8.35 ± 0.10 10 x M; p < 0.05 lean vs. obese, n = 6 per group). This difference was not apparent after AMPK inhibition (LogEC50 of ISO-developed pressure curves: lean CC -8.19 ± 0.12 vs. obese CC 8.17 ± 0.13 10 x M, p > 0.05, n = 6 per group

Changes in UCP expression in tissues of Zucker rats fed diets with different protein content.

PubMed

Masanés, R M; Yubero, P; Rafecas, I; Remesar, X

2002-09-01

The effect of dietary protein content on the uncoupling proteins (UCP) 1, 2 and 3 expression in a number of tissues of Zucker lean and obese rats was studied. Thirty-day-old male Zucker lean (Fa/?) and obese (fa/fa) rats were fed on hyperproteic (HP, 30% protein), standard (RD, 17% protein) or hypoproteic (LP, 9% protein) diets ad libitum for 30 days. Although dietary protein intake affected the weights of individual muscles in lean and obese animals, these weights were similar. In contrast, huge differences were observed in brown adipose tissue (BAT) and liver weights. Lean rats fed on the LP diet generally increased UCP expression, whereas the HP group had lower values. Obese animals, HP and LP groups showed higher UCP expression in muscles, with slight differences in BAT and lower values for UCP3 in subcutaneous adipose tissue. The mean values of UCP expression in BAT of obese rats were lower than in their lean counterpart, whereas the expression in skeletal muscle was increased. Thus, expression of UCPs can be modified by dietary protein content, in lean and obese rats. A possible thermogenic function of UCP3 in muscle and WAT in obese rats must be taken into account.

Effects of habitual exercise on the eHsp72-induced release of inflammatory cytokines by macrophages from obese Zucker rats.

PubMed

Garcia, J J; Martin-Cordero, L; Hinchado, M D; Bote, M E; Ortega, E

2013-06-01

Regular exercise is a good non-pharmacological treatment of metabolic syndrome in that it improves obesity, diabetes, and inflammation. The 72 kDa extracellular heat shock protein (eHsp72) is released during exercise, thus stimulating the inflammatory responses. The aim of the present work was to evaluate the effect of regular exercise on the eHsp72-induced release of IL-1β, IL-6, and TNFα by macrophages from genetically obese Zucker rats (fa/fa) (ObZ), using lean Zucker (LZ) rats (Fa/fa) to provide reference values. ObZ presented a higher plasma concentration of eHsp72 than LZ, and exercise increased that concentration. In response to eHsp72, the macrophages from ObZ released less IL-1β and TNFα, but more IL-6, than macrophages from LZ. While eHsp72 stimulated the release of IL-1β, TNFα, and IL-6 in the macrophages from healthy LZ (with respect to the constitutive release), it inhibited the release of IL-1β and IL-6 in macrophages from ObZ. The habitual exercise improved the release of inflammatory cytokines by macrophages from ObZ in response to eHsp72 (it increased IL-1β and TNFα, and decreased IL-6), tending to values closer to those determined in healthy LZ. A deregulated macrophage inflammatory and stress response induced by eHsp72 underlies MS, and this is improved by habitual exercise. © Georg Thieme Verlag KG Stuttgart · New York.

Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design.

PubMed

Bastarrachea, Raul A; Chen, Jiaxi; Kent, Jack W; Nava-Gonzalez, Edna J; Rodriguez-Ayala, Ernesto; Daadi, Marcel M; Jorge, Barbara; Laviada-Molina, Hugo; Comuzzie, Anthony G; Chen, Shuyuan; Grayburn, Paul A

2017-09-01

Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)-treated mice and baboons. We hypothesized that gene therapy with BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with UCP-1 overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD-based gene delivery in enhancing SKM overexpression of the UCP-1 gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of PRDM16, PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in vivo. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD

trans-trans Conjugated linoleic acid enriched soybean oil reduces fatty liver and lowers serum cholesterol in obese zucker rats.

PubMed

Gilbert, William; Gadang, Vidya; Proctor, Andrew; Jain, Vishal; Devareddy, Latha

2011-10-01

Conjugated linoleic acid (CLA) is a collection of octadecadienoic fatty acids that have been shown to possess numerous health benefits. The CLA used in our study was produced by the photoisomerization of soybean oil and consists of about 20% CLA; this CLA consists of 75% trans-trans (a mixture of t8,t10; t9,t11; t10,t12) isomers. This method could be readily used to increase the CLA content of all soybean oil used as a food ingredient. The objective of this study was to determine the effects of trans-trans CLA-rich soy oil, fed as a dietary supplement, on body composition, dyslipidemia, hepatic steatosis, and markers of glucose control and liver function of obese fa/fa Zucker rats. The trans-trans CLA-rich soy oil lowered the serum cholesterol and low density lipoprotein-cholesterol levels by 41 and 50%, respectively, when compared to obese controls. Trans-trans CLA-rich soy oil supplementation also lowered the liver lipid content significantly (P < 0.05) with a concomitant decrease in the liver weight in the obese rats. In addition, glycated hemoglobin values were improved in the group receiving CLA-enriched soybean oil in comparison to the obese control. PPAR-γ expression in white adipose tissue was unchanged. In conclusion, trans-trans CLA-rich soy oil was effective in lowering total liver lipids and serum cholesterol.

A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats

PubMed Central

French, William W.; Dridi, Sami; Shouse, Stephanie A.; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I.

2017-01-01

A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake (p < 0.05) compared to O20. O40 rats had lower liver weight (p < 0.05) compared to O20. However, O40 rats had higher orexin (p < 0.05) levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 (p < 0.05), with no difference in 5′ AMP-activated protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle. PMID:28594375

A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats.

PubMed

French, William W; Dridi, Sami; Shouse, Stephanie A; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I

2017-06-08

A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake ( p < 0.05) compared to O20. O40 rats had lower liver weight ( p < 0.05) compared to O20. However, O40 rats had higher orexin ( p < 0.05) levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 ( p < 0.05), with no difference in 5' AMP-activated protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

Serum adipokine profile and fatty acid composition of adipose tissues are affected by conjugated linoleic acid and saturated fat diets in obese Zucker rats.

PubMed

Martins, Susana V; Lopes, Paula A; Alfaia, Cristina M; Rodrigues, Pedro O; Alves, Susana P; Pinto, Rui M A; Castro, Matilde F; Bessa, Rui J B; Prates, José A M

2010-03-01

Conjugated linoleic acid (CLA) has been reported as having body fat lowering properties and the ability to modulate the inflammatory system in several models. In the present study, the effects of CLA added to saturated fat diets, from vegetable and animal origins, on the serum adipokine profile of obese Zucker rats were assessed. In addition, the fatty acid composition of epididymal and retroperitoneal adipose tissues was determined and a principal component analysis (PCA) was used to assess possible relationships between fatty acids and serum metabolites. Atherogenic diets (2 % cholesterol) were formulated with palm oil and ovine fat and supplemented or not with 1 % of a mixture (1:1) of cis-9, trans-11 and trans-10, cis-12-CLA isomers. CLA-fed animals exhibited lower daily feed intake, final body and liver weights, and hepatic lipids content. Total and LDL-cholesterol levels were increased in CLA-supplemented groups. CLA also promoted higher adiponectin and lower plasminogen activator inhibitor-1 (PAI-1) serum concentrations. In contrast to palm oil diets, ovine fat increased insulin resistance and serum levels of leptin, TNF-alpha and IL-1beta. Epididymal and retroperitoneal adipose tissues had similar deposition of individual fatty acids. The PCA analysis showed that the trans-10, cis-12-CLA isomer was highly associated with adiponectin and PAI-1 levels. Summing up, CLA added to vegetable saturated enriched diets, relative to those from animal origin, seems to improve the serum profile of adipokines and inflammatory markers in obese Zucker rats due to a more favourable fatty acid composition.

Dietary fish protein hydrolysates containing bioactive motifs affect serum and adipose tissue fatty acid compositions, serum lipids, postprandial glucose regulation and growth in obese Zucker fa/fa rats.

PubMed

Drotningsvik, Aslaug; Mjøs, Svein A; Pampanin, Daniela M; Slizyte, Rasa; Carvajal, Ana; Remman, Tore; Høgøy, Ingmar; Gudbrandsen, Oddrun A

2016-10-01

The world's fisheries and aquaculture industries produce vast amounts of protein-containing by-products that can be enzymatically hydrolysed to smaller peptides and possibly be used as additives to functional foods and nutraceuticals targeted for patients with obesity-related metabolic disorders. To investigate the effects of fish protein hydrolysates on markers of metabolic disorders, obese Zucker fa/fa rats consumed diets with 75 % of protein from casein/whey (CAS) and 25 % from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material, or 100 % protein from CAS for 4 weeks. The fatty acid compositions were similar in the experimental diets, and none of them contained any long-chain n-3 PUFA. Ratios of lysine:arginine and methionine:glycine were lower in HER and SAL diets when compared with CAS, and taurine was detected only in fish protein hydrolysate diets. Motifs with reported hypocholesterolemic or antidiabetic activities were identified in both fish protein hydrolysates. Rats fed HER diet had lower serum HDL-cholesterol and LDL-cholesterol, and higher serum TAG, MUFA and n-3:n-6 PUFA ratio compared with CAS-fed rats. SAL rats gained more weight and had better postprandial glucose regulation compared with CAS rats. Serum lipids and fatty acids were only marginally affected by SAL, but adipose tissue contained less total SFA and more total n-3 PUFA when compared with CAS. To conclude, diets containing hydrolysed rest raw material from herring or salmon proteins may affect growth, lipid metabolism, postprandial glucose regulation and fatty acid composition in serum and adipose tissue in obese Zucker rats.

Mixed compared with single-source proteins in high-protein diets affect kidney structure and function differentially in obese fa/fa Zucker rats.

PubMed

Devassy, Jessay G; Wojcik, Jennifer L; Ibrahim, Naser H M; Zahradka, Peter; Taylor, Carla G; Aukema, Harold M

2017-02-01

Questions remain regarding the potential negative effects of dietary high protein (HP) on kidney health, particularly in the context of obesity in which the risk for renal disease is already increased. To examine whether some of the variability in HP effects on kidney health may be due to source of protein, obese fa/fa Zucker rats were given HP (35% of energy from protein) diets containing either casein, soy protein, or a mixed source of animal and plant proteins for 12 weeks. Control lean and obese rats were given diets containing casein at normal protein (15% of energy from protein) levels. Body weight and blood pressure were measured, and markers of renal structural changes, damage, and function were assessed. Obesity alone resulted in mild renal changes, as evidenced by higher kidney weights, proteinuria, and glomerular volumes. In obese rats, increasing the protein level using the single, but not mixed, protein sources resulted in higher renal fibrosis compared with the lean rats. The mixed-protein HP group also had lower levels of serum monocyte chemoattractant protein-1, even though this diet further increased kidney and glomerular size. Soy and mixed-protein HP diets also resulted in a small number of damaged glomeruli, while soy compared with mixed-protein HP diet delayed the increase in blood pressure over time. Since obesity itself confers added risk of renal disease, an HP diet from mixed-protein sources that enables weight loss but has fewer risks to renal health may be advantageous.

ZO proteins redundantly regulate the transcription factor DbpA/ZONAB.

PubMed

Spadaro, Domenica; Tapia, Rocio; Jond, Lionel; Sudol, Marius; Fanning, Alan S; Citi, Sandra

2014-08-08

The localization and activities of DbpA/ZONAB and YAP transcription factors are in part regulated by the density-dependent assembly of epithelial junctions. DbpA activity and cell proliferation are inhibited by exogenous overexpression of the tight junction (TJ) protein ZO-1, leading to a model whereby ZO-1 acts by sequestering DbpA at the TJ. However, mammary epithelial cells and mouse tissues knock-out for ZO-1 do not show increased proliferation, as predicted by this model. To address this discrepancy, we examined the localization and activity of DbpA and YAP in Madin-Darby canine kidney cells depleted either of ZO-1, or one of the related proteins ZO-2 and ZO-3 (ZO proteins), or all three together. Depletion of only one ZO protein had no effect on DbpA localization and activity, whereas depletion of ZO-1 and ZO-2, which is associated with reduced ZO-3 expression, resulted in increased DbpA localization in the cytoplasm. Only depletion of ZO-2 reduced the nuclear import of YAP. Mammary epithelial (Eph4) cells KO for ZO-1 showed junctional DbpA, demonstrating that ZO-1 is not required to sequester DbpA at junctions. However, further depletion of ZO-2 in Eph4 ZO-1KO cells, which do not express ZO-3, caused decreased junctional localization and expression of DbpA, which were rescued by the proteasome inhibitor MG132. In vitro binding assays showed that full-length ZO-1 does not interact with DbpA. These results show that ZO-2 is implicated in regulating the nuclear shuttling of YAP, whereas ZO proteins redundantly control the junctional retention and stability of DbpA, without affecting its shuttling to the nucleus. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Roles of ZO-1 and ZO-2 in establishment of the belt-like adherens and tight junctions with paracellular permselective barrier function.

PubMed

Tsukita, Sachiko; Katsuno, Tatsuya; Yamazaki, Yuji; Umeda, Kazuaki; Tamura, Atsushi; Tsukita, Shoichiro

2009-05-01

Tight junctions (TJs) create the primary permselective barrier to diffusion of solutes and ions through the paracellular pathway. The molecular architecture of TJs has gradually been unraveled in recent years, providing the basis for "barriology" (defined by Shoichiro Tsukita as the science of the barrier in multicellular organisms). Claudins are now considered to be the essential basic components of TJ strands, with which other integral membrane proteins, such as occludin, tricellulin, JAMs, and CAR, are associated. Peripherally associated scaffolding proteins are required for the organization of the integral membrane proteins. Among these, ZO-1, -2, and -3 have attracted a great deal of attention as TJ organizers, since ZO-1 (and in some cases, also ZO-2/3) was reported to be directly associated with claudins, occludin, and JAMs, as well as with AF-6/afadin and alpha-catenin. Here we summarize recent studies on ZO-1/2/3-deficiency in mice and cells, which have provided clear and important information regarding the functions of ZO-1/2/3 in vivo. In addition to the respective suppression of ZO-1/2/3 expression, simultaneous suppression of all three proteins has revealed the essential and nonessential in vivo roles of ZO-1/2 and ZO-3, respectively. ZO-3 shows an epithelial-specific TJ localization in a ZO-1/2-dependent fashion. ZO-1 and ZO-2 play pivotal roles in the final establishment of the belt-like adherens junctions (zonula adherens), followed by the formation of the belt-like TJs (zonula occludens) with paracellular barrier function, thereby providing the general basis for selective paracellular permeability in epithelial and endothelial cells.

Effects of obesity on IL-33/ST2 system in heart, adipose tissue and liver: study in the experimental model of Zucker rats.

PubMed

Ragusa, Rosetta; Cabiati, Manuela; Guzzardi, Maria Angela; D'Amico, Andrea; Giannessi, Daniela; Del Ry, Silvia; Caselli, Chiara

2017-04-01

Suppression of tumorigenicity 2 (ST2) mediates the effect of Interleukin-33 (IL-33). Few data are reported on the relationship between IL-33/ST2 and obesity. We aimed to investigate effects of obesity on IL-33/ST2 system in heart, adipose tissue and liver in a rodent model of obesity. The relationship of cardiac expression of IL-33/ST2 system with natriuretic peptides (NPs) system and inflammatory mediators was also studied. mRNA expression of IL-33/ST2 system was evaluated in cardiac, adipose and hepatic biopsies from obese Zucker rats (O) and controls (CO). Expression levels of sST2 was significantly lower in O rats compared with CO (p<0.05) in all tissues. Besides, the mRNA levels of IL-33 decreased significant in fat of O respect to CO, while, expression levels of ST2L was significantly higher in liver of CO than in O. A strong relationship of IL-33/ST2 with NPs and classical inflammatory mediators was observed in cardiac tissue. Expression of sST2 in cardiac, adipose and liver tissue decreased in O compared with controls, suggesting an involvement for IL-33/ST2 system in molecular mechanisms of obesity. The strong relationships with NP systems and inflammatory mediators could suggest an involvement for IL-33/ST2 in molecular pathways leading to cardiac dysfunction and inflammation associated with obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile

PubMed Central

Ruiz-Hurtado, Gema; García-Prieto, Concha F.; Pulido-Olmo, Helena; Velasco-Martín, Juan P.; Villa-Valverde, Palmira; Fernández-Valle, María E.; Boscá, Lisardo; Fernández-Velasco, María; Regadera, Javier; Somoza, Beatriz; Fernández-Alfonso, María S.

2017-01-01

Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30–65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile. PMID:28203206

Gene expression and adiposity are modified by soy protein in male Zucker diabetic fatty rats.

PubMed

Banz, William J; Davis, Jeremy; Peterson, Richard; Iqbal, Muhammad J

2004-12-01

It has earlier been demonstrated that soy protein diets ameliorate the diabetic phenotype in obese Zucker rats. In this study, we further investigated physiological changes related to adiposity in male Zucker diabetic fatty rats consuming soy-based diets and compared these diets with the insulin-sensitizing drug, rosiglitazone. Transcript abundance of known genes was assessed in the livers to identify potential molecular connections between soy diets and adiposity. Male Zucker diabetic fatty rats were assigned to casein (C) protein, low-isoflavone soy (LIS) protein, high-isoflavone soy (HIS) protein, or C + rosiglitazone (CR) diets. Compared with the C diet, the LIS diet decreased plasma lipids and increased body weight, but did not change liver weight or carcass adiposity. HIS decreased plasma lipids, liver weight, and body weight. CR decreased plasma lipids and increased carcass adiposity and body weight with no effect on liver weight. In LIS livers, 15 genes involved in signaling and lipid metabolism were up-regulated 2-fold or higher. In HIS livers, seven genes had a 2-fold or higher change in abundance. However, in CR livers, none of the genes was significantly changed compared with the C diet. There appears to be a distinct change in gene expression associated with soy diets as compared with C-based diets and rosiglitazone treatment.

Relationship between lipogenesis, ketogenesis, and malonyl-CoA content in isolated hepatocytes from the obese Zucker rat adapted to a high-fat diet.

PubMed

Malewiak, M I; Griglio, S; Le Liepvre, X

1985-07-01

The relationship between lipogenesis and ketogenesis and the concentration of malonyl coenzyme A (CoA) was investigated in hepatocytes from adult obese Zucker rats and their lean littermates fed either a control low-fat diet or a high-fat diet (30% lard in weight). With the control diet, lipogenesis--although strongly inhibited in the presence of either 1 mmol/L oleate, 10(-6) mol/L glucagon or 0.1 mmol/L TOFA (a hypolipidemic drug)--remained about fifteen-fold higher in the obese rats than in the lean rats. In contrast, ketogenesis under some conditions (oleate + TOFA) was not significantly lower (30%) as compared with the lean rats. After adaptation to the high-fat diet, lipogenesis was depressed fourfold in the lean rats and ninefold in the obese ones; however its magnitude remained significantly higher in the latter, namely at a value close to that measured in control-fed lean rats. Ketogenesis was comparable in lean and obese rats and much higher in the presence of 1 mmol/L oleate than of 0.3 mmol/L oleate, whereas lipogenesis did not vary with increasing oleate concentration in the medium. Acetyl-CoA carboxylase activity measured in liver homogenates was higher in the obese group, but was stepwise inhibited by increasing concentrations of oleyl-CoA regardless of the diet for both lean and obese rats, thus showing no abnormality of in vitro responsiveness to this inhibitor. With the control diet, hepatocyte malonyl-CoA levels were significantly higher in the obese rats, both in the basal state and after inhibition of lipogenesis by oleate and TOFA.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered Expression of ZO-1 and ZO-2 in Sertoli Cells and Loss of Blood-Testis Barrier Integrity in Testicular Carcinoma In Situ1

PubMed Central

Fink, Cornelia; Weigel, Roswitha; Hembes, Tanja; Lauke-Wettwer, Heidrun; Kliesch, Sabine; Bergmann, Martin; Brehm, Ralph H

2006-01-01

Abstract Carcinoma in situ (CIS) is the noninvasive precursor of most human testicular germ cell tumors. In normal seminiferous epithelium, specialized tight junctions between Sertoli cells constitute the major component of the blood-testis barrier. Sertoli cells associated with CIS exhibit impaired maturation status, but their functional significance remains unknown. The aim was to determine whether the blood-testis barrier is morphologically and/or functionally altered. We investigated the expression and distribution pattern of the tight junction proteins zonula occludens (ZO) 1 and 2 in normal seminiferous tubules compared to tubules showing CIS. In normal tubules, ZO-1 and ZO-2 immunostaining was observed at the blood-testis barrier region of adjacent Sertoli cells. Within CIS tubules, ZO-1 and ZO-2 immunoreactivity was reduced at the blood-testis barrier region, but spread to stain the Sertoli cell cytoplasm. Western blot analysis confirmed ZO-1 and ZO-2, and their respective mRNA were shown by RT-PCR. Additionally, we assessed the functional integrity of the blood-testis barrier by lanthanum tracer study. Lanthanum permeated tight junctions in CIS tubules, indicating disruption of the blood-testis barrier. In conclusion, Sertoli cells associated with CIS show an altered distribution of ZO-1 and ZO-2 and lose their blood-testis barrier function. PMID:17217619

Vitamin A status affects obesity development and hepatic expression of key genes for fuel metabolism in Zucker fatty rats.

PubMed

Zhang, Yan; Li, Rui; Li, Yang; Chen, Wei; Zhao, Shi; Chen, Guoxun

2012-08-01

We hypothesized that vitamin A (VA) status may affect obesity development. Male Zucker lean (ZL) and fatty (ZF) rats after weaning were fed a synthetic VA deficient (VAD) or VA sufficient (VAS) diet for 8 weeks before their plasma parameters and hepatic genes' expression were analyzed. The body mass (BM) of ZL or ZF rats fed the VAD diet was lower than that of their corresponding controls fed the VAS diet at 5 or 2 weeks, respectively. The VAD ZL and ZF rats had less food intake than the VAS rats after 5 weeks. The VAD ZL and ZF rats had lower plasma glucose, triglyceride, insulin, and leptin levels, as well as lower liver glycogen content, net mass of epididymal fat, and liver/BM and epididymal fat/BM ratios (ZL only) than their respective VAS controls. VAD rats had lower hepatic Cyp26a1, Srebp-1c, Fas, Scd1, Me1, Gck, and Pklr (ZL and ZF); and higher Igfbp1 (ZL and ZF), Pck1(ZF only), and G6pc (ZF only) mRNA levels than their respective VAS controls. We conclude that ZL and ZF rats responded differently to dietary VA deficiency. VA status affected obesity development and altered the expression of hepatic genes for fuel metabolism in ZF rats. The mechanisms will help us to combat metabolic diseases.

Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats.

PubMed

Luck, Christian; DeMarco, Vincent G; Mahmood, Abuzar; Gavini, Madhavi P; Pulakat, Lakshmi

2017-01-01

Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750  μ g/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters ( E / E ', E '/ A ', E / Vp ) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFN γ , and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.

Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

PubMed Central

Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

2017-01-01

Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes. PMID:28408970

Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

PubMed

Kapravelou, Garyfallia; Martínez, Rosario; Andrade, Ana M; Nebot, Elena; Camiletti-Moirón, Daniel; Aparicio, Virginia A; Lopez-Jurado, Maria; Aranda, Pilar; Arrebola, Francisco; Fernandez-Segura, Eduardo; Bermano, Giovanna; Goua, Marie; Galisteo, Milagros; Porres, Jesus M

2015-12-01

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P < 0.0001) and suffered significant alterations in plasma lipid profile, area under the curve after oral glucose overload (P < 0.0001), liver histology and functionality, and antioxidant status. The AIT protocol reduced the severity of alterations related to glucose and lipid metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

Immune function, mitogenicity, and angiogenic growth factor concentrations in lean and obese rodent sera: implications in obesity-related prostate tumor biology.

PubMed

Mydlo, J H; Gerstein, M I; Harris, C F; Braverman, A S

2003-01-01

Some studies suggest that several tumors have a greater incidence in those patients with a high fat diet, such as colon, breast, and prostate. However, we wanted to determine the effects of obesity alone, independent of diet, on the progression of prostate tumor growth. Using a genetic model of obese and lean Zucker rats, we wanted to demonstrate any sera differences in the concentration of basic fibroblast growth factor (FGF-2) and vascular endothelial cell growth factor (VEGF), two important factors involved in the growth and progression of prostate cancer. We also wanted to investigate if there were any differences in immune function between the two sera, which could also account for uninhibited tumor growth, as well as differences in mitogenic stimulation. Female Zucker rat obese and lean sera were analyzed using ELISA assays for FGF-2, VEGF, and macrophage inflammatory protein-1 alpha (MIP-1a), as a measure of macrophage function. In addition, the sera of lean and obese sera were plated on wells growing LNCaP prostate cancer cells to determine differences in mitogenicity. We found a greater concentration of FGF-2 in the sera from obese Zucker rats compared to lean Zucker rats: 6.32+/-0.56 vs 3.48+/-0.34 pg/ml, respectively, P<0.05). We also demonstrated a greater concentration of VEGF in obese rat sera compared to lean sera: 54.4+/-4.1 vs 38.0+/-2.9 pg/mL, respectively, P<0.05). We detected a trend in mitogenic stimulation among LNCaP cells along the higher concentrations of the dose-response curve (0.72+/-0.06 vs 0.51+/-0.5). However, this was not statistically significant. In addition, we did not find a significant difference in MIP-1a macrophage activity levels between sera. To conclude, we speculate that the greater concentrations of VEGF and FGF-2 in the sera of obese rodents vs lean rodents may account for some of the differences seen in obesity-related tumor growth seen in the human condition. However, the lack of any sera differences of immune function

Neuronal connexin36 association with zonula occludens-1 protein (ZO-1) in mouse brain and interaction with the first PDZ domain of ZO-1

PubMed Central

Li, Xinbo; Olson, Carl; Lu, Shijun; Kamasawa, Naomi; Yasumura, Thomas; Rash, John E.; Nagy, James I.

2007-01-01

Among the 20 members in the connexin family of gap junction proteins, only connexin36 (Cx36) is firmly established to be expressed in neurons and to form electrical synapses at widely distributed interneuronal gap junctions in mammalian brain. Several connexins have recently been reported to interact with the PDZ domain-containing protein zonula occludens-1 (ZO-1), which was originally considered to be associated only with tight junctions, but has recently been reported to associate with other structures including gap junctions in various cell types. Based on the presence of sequence corresponding to a putative PDZ binding motif in Cx36, we investigated anatomical relationships and molecular association of Cx36 with ZO-1. By immunofluorescence, punctate Cx36/ZO-1 colocalization was observed throughout the central nervous system of wild-type mice, whereas labelling for Cx36 was absent in Cx36 knockout mice, confirming the specificity of the anti-Cx36 antibodies employed. By freeze-fracture replica immunogold labelling, Cx36 and ZO-1 in brain were found colocalized within individual ultrastructurally identified gap junction plaques, although some plaques contained only Cx36 whereas others contained only ZO-1. Cx36 from mouse brain and Cx36-transfected HeLa cells was found to coimmunoprecipitate with ZO-1. Unlike other connexins that bind the second of the three PDZ domains in ZO-1, glutathione S-transferase-PDZ pull-down and mutational analyses indicated Cx36 interaction with the first PDZ domain of ZO-1, which required at most the presence of the four c-terminus amino acids of Cx36. These results demonstrating a Cx36/ZO-1 association suggest a regulatory and/or scaffolding role of ZO-1 at gap junctions that form electrical synapses between neurons in mammalian brain. PMID:15090040

Tissue-specific selection of stable reference genes for real-time PCR normalization in an obese rat model.

PubMed

Cabiati, Manuela; Raucci, Serena; Caselli, Chiara; Guzzardi, Maria Angela; D'Amico, Andrea; Prescimone, Tommaso; Giannessi, Daniela; Del Ry, Silvia

2012-06-01

Obesity is a complex pathology with interacting and confounding causes due to the environment, hormonal signaling patterns, and genetic predisposition. At present, the Zucker rat is an eligible genetic model for research on obesity and metabolic syndrome, allowing scrutiny of gene expression profiles. Real-time PCR is the benchmark method for measuring mRNA expressions, but the accuracy and reproducibility of its data greatly depend on appropriate normalization strategies. In the Zucker rat model, no specific reference genes have been identified in myocardium, kidney, and lung, the main organs involved in this syndrome. The aim of this study was to select among ten candidates (Actb, Gapdh, Polr2a, Ywhag, Rpl13a, Sdha, Ppia, Tbp, Hprt1 and Tfrc) a set of reference genes that can be used for the normalization of mRNA expression data obtained by real-time PCR in obese and lean Zucker rats both at fasting and during acute hyperglycemia. The most stable genes in the heart were Sdha, Tbp, and Hprt1; in kidney, Tbp, Actb, and Gapdh were chosen, while Actb, Ywhag, and Sdha were selected as the most stably expressed set for pulmonary tissue. The normalization strategy was used to analyze mRNA expression of tumor necrosis factor α, the main inflammatory mediator in obesity, whose variations were more significant when normalized with the appropriately selected reference genes. The findings obtained in this study underline the importance of having three stably expressed reference gene sets for use in the cardiac, renal, and pulmonary tissues of an experimental model of obese and hyperglycemic Zucker rats.

Genetic predisposition to obesity affects behavioural traits including food reward and anxiety-like behaviour in rats.

PubMed

Vogel, Heike; Kraemer, Maria; Rabasa, Cristina; Askevik, Kaisa; Adan, Roger A H; Dickson, Suzanne L

2017-06-15

Here we sought to define behavioural traits linked to anxiety, reward, and exploration in different strains of rats commonly used in obesity research. We hypothesized that genetic variance may contribute not only to their metabolic phenotype (that is well documented) but also to the expression of these behavioural traits. Rat strains that differ in their susceptibility to develop an obese phenotype (Sprague-Dawley, Obese Prone, Obese Resistant, and Zucker rats) were exposed to a number of behavioural tests starting at the age of 8 weeks. We found a similar phenotype in the obesity susceptible models, Obese Prone and Zucker rats, with a lower locomotor activity, exploratory activity, and higher level of anxiety-like behaviour in comparison to the leaner Obese Resistant strain. We did not find evidence that rat strains with a genetic predisposition to obesity differed in their ability to experience reward from chocolate (in a condition place preference task). However, Zucker rats show higher motivated behaviour for sucrose compared to Obese Resistant rats when the effort required to obtain palatable food is relatively low. Together our data demonstrate that rat strains that differ in their genetic predisposition to develop obesity also differ in their performance in behavioural tests linked to anxiety, exploration, and reward and that these differences are independent of body weight. We conclude that genetic variations which determine body weight and the aforementioned behaviours co-exist but that future studies are required to identify whether (and which) common genes are involved. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of xanthine oxidase inhibition with febuxostat on the development of nephropathy in experimental type 2 diabetes.

PubMed

Komers, Radko; Xu, Bei; Schneider, Jennifer; Oyama, Terry T

2016-09-01

Elevated serum uric acid (UA) is a risk factor for the development of kidney disease. Inhibitors of xanthine oxidase (XOi), an enzyme involved in UA synthesis, have protective effects at early stages of experimental diabetic nephropathy (DN). However, long-term effects of XOi in models of DN remain to be determined. The development of albuminuria, renal structure and molecular markers of DN were studied in type 2 diabetic Zucker obese (ZO) rats treated for 18 weeks with the XOi febuxostat and compared with vehicle-treated ZO rats, ZO rats treated with enalapril or a combination of both agents, and lean Zucker rats without metabolic defects. Febuxostat normalized serum UA and attenuated the development of albuminuria, renal structural changes, with no significant effects on BP, metabolic control or systemic markers of oxidative stress (OS). Most of these actions were comparable with those of enalapril. Combination treatment induced marked decreases in BP and was more effective in ameliorating structural changes, expression of profibrotic genes and systemic OS than either monotherapy. Febuxostat attenuated renal protein expression of TGF-ß, CTGF, collagen 4, mesenchymal markers (FSP1 and vimentin) and a tissue marker of OS nitrotyrosine. Moreover, febuxostat attenuated TGF-ß- and S100B-induced increased expression of fibrogenic molecules in renal tubular cells in vitro in UA-free media in an Akt kinase-dependent manner. Febuxostat is protective and enhances the actions of enalapril in experimental DN. Multiple mechanisms might be involved, such as a reduction of UA, renal OS and inhibition of profibrotic signalling. © 2016 The British Pharmacological Society.

Ciprofibrate, clofibric acid and respective glycinate derivatives. Effects of a four-week treatment on male lean and obese Zucker rats.

PubMed

Lupp, Amelie; Karge, Elke; Deufel, Thomas; Oelschlägers, Herbert; Fleck, Christian

2008-01-01

Fibrates are widely prescribed in hyperlpidemic patients to prevent atherosclerosis. Their therapeutic use, however, can be associated with adverse effects like gastrointestinal disorders, myalgia, myositis and hepatotoxicity. In rodents large doses can even cause hepatocellular carcinoma. Additionally, interactions with the biotransformation of other compounds at the cytochrome P450 (CYP) system have been observed. Thus, the discovery of new substances or derivatives with less side effects is of great interest. In the present study the influence of a four-week daily oral administration of 2 mg/kg body weight ciprofibrate (CAS 52214-84-3) or of 100 mg/kg body weight clofibric acid (CAS 882-09-7) was compared to that of the respective doses of their newly synthesized glycine conjugates in adult male lean and obese Zucker rats. Although obese rats displayed distinctly higher serum lipid concentrations, after fibrate treatment values were significantly lowered in lean animals only. Livers of obese rats were significantly enlarged, histologically showing a fine-droplet like fatty degeneration and an increase in glycogen content, but no signs of inflammation. After fibrate administration histologically a hypertrophy, an eosinophilia, a reduced glycogen content and also hepatocyteapoptosis were observed. Livers of obese rats displayed higher CYP1A1 andCYP2E1 expression, but lower immunostaining for CYP2B1 and CYP3A2. No differences between the two groups of rats were seen with respect to CYP4A1 expression. Due to fibrate treatment especially CYP2E1 and CYP4A1, but also CYP1A1, 2B1 and 3A2 were induced. Resulting CYP mediated monooxygenase activities were also elevated in most cases. In general, effects of clofibric acid and clofibric acid glycinate (CAS 4896-55-3) were less distinct than those of ciprofibrate and its glycinate (CAS 640772-36-7). With no parameterinvestigated major differences were seen between the parent fibrates and their glycine conjugates. Thus, the

Hydroxypropyl methylcellulose, a viscous soluble fiber, reduces insulin resistance and decreases fatty liver in Zucker Diabetic Fatty rats.

PubMed

Brockman, David A; Chen, Xiaoli; Gallaher, Daniel D

2012-11-12

Diets producing a high glycemic response result in exaggerated insulin secretion which induces hepatic lipogenesis, contributing to development of insulin resistance and fatty liver. Viscous dietary fibers blunt the postprandial rise in blood glucose, however their effect on type 2 diabetes and obesity are not entirely known. This study examined the effect of chronic consumption of the viscous, non-fermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), on glucose control, insulin resistance and liver lipids in an obese diabetic rat model. Three groups of Zucker Diabetic Fatty (ZDF) rats were fed diets containing either 5% non-viscous cellulose (control), low viscosity HPMC (LV-HPMC) or high viscosity HPMC (HV- HPMC) for six weeks. Zucker lean littermates consuming cellulose served as a negative control. Markers of glucose control, including oral glucose tolerance test, glycated hemoglobin and urinary glucose, were measured as well as adiposity and the accumulation of liver lipids. The HPMC diets increased the viscosity of the small intestinal contents and reduced the postprandial rise in blood glucose. The food efficiency ratio was greater with HPMC feeding compared to the obese control and urinary excretion of glucose and ketone bodies was reduced. The two HPMC groups had lower glycated hemoglobin and kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Epididymal fat pad weight as percent of body weight was reduced in the HV-HPMC group compared to the obese control group. The HV-HPMC group also had lower concentrations of liver lipid and cholesterol and reduced liver weight. However, HV-HPMC feeding did not affect hepatic gene expression of SREBP-1c or FAS. Muscle concentration of acylcarnitines, a lipid intermediate in fatty acid β-oxidation, was not different between the HPMC groups and obese control, suggesting no change in muscle fatty acid oxidation by HPMC. Consumption of the

Influence of exercise on NA- and Hsp72-induced release of IFNγ by the peritoneal suspension of macrophages and lymphocytes from genetically obese Zucker rats.

PubMed

Martín-Cordero, L; García, J J; Hinchado, M D; Bote, E; Ortega, E

2013-03-01

Regular physical exercise is recognized as a nonpharmacological therapeutic strategy in the treatment of metabolic syndrome, and has been proposed for improving obesity, diabetic status, insulin resistance, and immune response. The aim of the present study was to evaluate the effect of a regular exercise program (treadmill running, 5 days/week for 14 weeks at 35 cm/s for 35 min in the last month) on the release of the pro-inflammatory cytokine interferon gamma (IFNγ) by peritoneal cells (macrophages and lymphocytes) from obese Zucker rats (fa/fa) in response to noradrenaline (NA) and heat shock proteins of 72 kDa (Hsp72), and the possible adaptation due to training for a bout acute exercise (a single session of 25-35 min at 35 cm/s). In healthy (lean Fa/fa) and obese animals, peritoneal cells released greater concentrations of IFNγ in response to Hsp72 and lower concentrations in response to NA. The regular exercise training protocol, evaluated in the obese animals, produced a clear change in the regulation of the release of IFNγ. Peritoneal immune cells from trained animals released more IFNγ in response to NA, but there was a reduction in the release of IFNγ in response to Hsp72. In the obese animals, regular exercise caused a change in the inhibitory effect of NA (which now becomes stimulatory) and the stimulatory effect of Hsp72e (which now becomes inhibitory) in relation to the release of IFNγ. This reflects that Hsp72, induced by the prior release of NA following exercise-induced stress, plays a role in the homeostatic balance of release of IFNγ by peritoneal immune cells in obese animals during exercise.

Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling.

PubMed

Nolan, C J; Leahy, J L; Delghingaro-Augusto, V; Moibi, J; Soni, K; Peyot, M-L; Fortier, M; Guay, C; Lamontagne, J; Barbeau, A; Przybytkowski, E; Joly, E; Masiello, P; Wang, S; Mitchell, G A; Prentki, M

2006-09-01

The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes. NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats. Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l). Exogenous palmitate also synergised with glucagon-like peptide-1 and the cyclic AMP-raising agent forskolin to enhance GSIS in ZF islets only. In assessing islet fatty acid metabolism, we found increased glucose-responsive palmitate esterification and lipolysis processes in ZF islets, suggestive of enhanced triglyceride-fatty acid cycling. Interruption of glucose-stimulated lipolysis by the lipase inhibitor Orlistat (tetrahydrolipstatin) blunted palmitate-augmented GSIS in ZF islets. Fatty acid oxidation was also higher at intermediate glucose levels in ZF islets and steatotic triglyceride accumulation was absent. The results highlight the potential importance of NEFA and glucoincretin enhancement of insulin secretion in beta cell compensation for insulin resistance. We propose that coordinated glucose-responsive fatty acid esterification and lipolysis processes, suggestive of triglyceride-fatty acid cycling, play a role in the coupling mechanisms of glucose-induced insulin secretion as well as in beta cell compensation and the hypersecretion of insulin in obesity.

Pancreatic Fat Accumulation, Fibrosis, and Acinar Cell Injury in the Zucker Diabetic Fatty Rat Fed a Chronic High-Fat Diet

PubMed Central

Matsuda, Akiko; Makino, Naohiko; Tozawa, Tomohiro; Shirahata, Nakao; Honda, Teiichiro; Ikeda, Yushi; Sato, Hideyuki; Ito, Miho; Kakizaki, Yasuharu; Akamatsu, Manabu; Ueno, Yoshiyuki; Kawata, Sumio

2014-01-01

Objective The histological alteration of the exocrine pancreas in obesity has not been clarified. In the present study, we investigated biochemical and histological changes in the exocrine pancreas of obese model rats. Methods Zucker lean rats were fed a standard diet, and Zucker diabetic fatty (ZDF) rats were divided into 2 groups fed a standard diet and a high-fat diet, respectively. These experimental groups were fed each of the diets from 6 weeks until 12, 18, 24 weeks of age. We performed blood biochemical assays and histological analysis of the pancreas. Results In the ZDF rats fed a high-fat diet, the ratio of accumulated pancreatic fat area relative to exocrine gland area was increased significantly at 18 weeks of age in comparison with the other 2 groups (P < 0.05), and lipid droplets were observed in acinar cells. Subsequently, at 24 weeks of age in this group, pancreatic fibrosis and the serum exocrine pancreatic enzyme levels were increased significantly relative to the other 2 groups (P < 0.01). Conclusions In ZDF rats fed a chronic high-fat diet, fat accumulates in pancreatic acinar cells, and this fatty change seems to be related to subsequent pancreatic fibrosis and acinar cell injury. PMID:24717823

Energy utilization of a low carbohydrate diet fed genetically obese rats and mice.

PubMed

Thenen, S W; Mayer, J

1977-02-01

Genetically obese Zucker rats, ob/ob mice and non-obese littermates were fed low carbohydrate (2%, 48%, and 50% of energy as carbohydrate, protein, and fat, respectively) and control (60%, 19%, and 21%, as carobhydrate, protein, and fat) diets. The oxidation of the energy components of these diets was measured by adding D-[U-14C]glucose, L-[U-14C]glutamic acid, and glyceryl tri-[1-14C]oleate to test meals given intragastrically and collecting respiratory CO2 for 4 hours. The animals responded to the low carbohydrate diet by oxidizing less glucose and more glutamic acid, but these amounts were proportional to dietary carbohydrate and protein composition, In contrast, the animals oxidized both higher amounts and percentages of glyceryl trioleate when fed the low carbohydrate diet. Obese Zucker rats oxidized less fat than non-obese rats when fed both diets, while obese mice oxidized fat to the same extent as non-obese mice. Feeding the low carbohydrate diet significantly increased body weight in the obese mice, but not in obese rats and non-obese mice and rats. The effect of obesity and the low carbohydrate diet on food intake, serum glucose and lipid values and CO2 production are also reported.

Alpha-Lipoic Acid Reduces LDL-Particle Number and PCSK9 Concentrations in High-Fat Fed Obese Zucker Rats

PubMed Central

Carrier, Bradley; Wen, Shin; Zigouras, Sophia; Browne, Richard W.; Li, Zhuyun; Patel, Mulchand S.; Williamson, David L.; Rideout, Todd C.

2014-01-01

We characterized the hypolipidemic effects of alpha-lipoic acid (LA, R-form) and examined the associated molecular mechanisms in a high fat fed Zucker rat model. Rats (n = 8) were assigned to a high fat (HF) diet or the HF diet with 0.25% LA (HF-LA) for 30 days and pair fed to remove confounding effects associated with the anorectic properties of LA. Compared with the HF controls, the HF-LA group was protected against diet-induced obesity (102.5±3.1 vs. 121.5±3.6,% change BW) and hypercholesterolemia with a reduction in total-C (−21%), non-HDL-C (−25%), LDL-C (−16%), and total LDL particle number (−46%) and an increase in total HDL particles (∼22%). This cholesterol-lowering response was associated with a reduction in plasma PCSK9 concentration (−70%) and an increase in hepatic LDLr receptor protein abundance (2 fold of HF). Compared with the HF-fed animals, livers of LA-supplemented animals were protected against TG accumulation (−46%), likely through multiple mechanisms including: a suppressed lipogenic response (down-regulation of hepatic acetyl-CoA carboxylase and fatty acid synthase expression); enhanced hepatic fat oxidation (increased carnitine palmitoyltransferase Iα expression); and enhanced VLDL export (increased hepatic diacylglycerol acyltransferase and microsomal triglyceride transfer protein expression and elevated plasma VLDL particle number). Study results also support an enhanced fatty acid uptake (2.8 fold increase in total lipase activity) and oxidation (increased CPT1β protein abundance) in muscle tissue in LA-supplemented animals compared with the HF group. In summary, in the absence of a change in caloric intake, LA was effective in protecting against hypercholesterolemia and hepatic fat accumulation under conditions of strong genetic and dietary predisposition toward obesity and dyslipidemia. PMID:24595397

Leucine and protein metabolism in obese zucker rats

USDA-ARS?s Scientific Manuscript database

Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however they increase in obesity and appear to prognosticate diabetes onset. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1...

Effects of xanthine oxidase inhibition with febuxostat on the development of nephropathy in experimental type 2 diabetes

PubMed Central

Xu, Bei; Schneider, Jennifer; Oyama, Terry T

2016-01-01

Background and Purpose Elevated serum uric acid (UA) is a risk factor for the development of kidney disease. Inhibitors of xanthine oxidase (XOi), an enzyme involved in UA synthesis, have protective effects at early stages of experimental diabetic nephropathy (DN). However, long‐term effects of XOi in models of DN remain to be determined. Experimental Approach The development of albuminuria, renal structure and molecular markers of DN were studied in type 2 diabetic Zucker obese (ZO) rats treated for 18 weeks with the XOi febuxostat and compared with vehicle‐treated ZO rats, ZO rats treated with enalapril or a combination of both agents, and lean Zucker rats without metabolic defects. Results Febuxostat normalized serum UA and attenuated the development of albuminuria, renal structural changes, with no significant effects on BP, metabolic control or systemic markers of oxidative stress (OS). Most of these actions were comparable with those of enalapril. Combination treatment induced marked decreases in BP and was more effective in ameliorating structural changes, expression of profibrotic genes and systemic OS than either monotherapy. Febuxostat attenuated renal protein expression of TGF‐ß, CTGF, collagen 4, mesenchymal markers (FSP1 and vimentin) and a tissue marker of OS nitrotyrosine. Moreover, febuxostat attenuated TGF‐ß‐ and S100B‐induced increased expression of fibrogenic molecules in renal tubular cells in vitro in UA‐free media in an Akt kinase‐dependent manner. Conclusions and Implications Febuxostat is protective and enhances the actions of enalapril in experimental DN. Multiple mechanisms might be involved, such as a reduction of UA, renal OS and inhibition of profibrotic signalling. PMID:27238746

Genetic profiling of two phenotypically distinct outbred rats derived from a colony of the Zucker fatty rats maintained at Tokyo Medical University

PubMed Central

Nakanishi, Satoshi; Kuramoto, Takashi; Kashiwazaki, Naomi; Yokoi, Norihide

2016-01-01

The Zucker fatty (ZF) rat is an outbred rat and a well-known model of obesity without diabetes, harboring a missense mutation (fatty, abbreviated as fa) in the leptin receptor gene (Lepr). Slc:Zucker (Slc:ZF) outbred rats exhibit obesity while Hos:ZFDM-Leprfa (Hos:ZFDM) outbred rats exhibit obesity and type 2 diabetes. Both outbred rats have been derived from an outbred ZF rat colony maintained at Tokyo Medical University. So far, genetic profiles of these outbred rats remain unknown. Here, we applied a simple genotyping method using Ampdirect reagents and FTA cards (Amp-FTA) in combination with simple sequence length polymorphisms (SSLP) markers to determine genetic profiles of Slc:ZF and Hos:ZFDM rats. Among 27 SSLP marker loci, 24 loci (89%) were fixed for specific allele at each locus in Slc:ZF rats and 26 loci (96%) were fixed in Hos:ZFDM rats, respectively. This indicates the low genetic heterogeneity in both colonies of outbred rats. Nine loci (33%) showed different alleles between the two outbred rats, suggesting considerably different genetic profiles between the two outbred rats in spite of the same origin. Additional analysis using 72 SSLP markers further supported these results and clarified the profiles in detail. This study revealed that genetic profiles of the Slc:ZF and Hos:ZFDM outbred rats are different for about 30% of the SSLP marker loci, which is the underlying basis for the phenotypic difference between the two outbred rats. PMID:27795491

Evaluation of Visceral Adipose Tissue Oxygenation by Blood Oxygen Level-Dependent MRI in Zucker Diabetic Fatty Rats.

PubMed

Shi, Hong-Jian; Li, Yan-Feng; Ji, Wen-Jie; Lin, Zhi-Chun; Cai, Wei; Chen, Tao; Yuan, Bin; Niu, Xiu-Long; Li, Han-Ying; Shu, Wen; Li, Yu-Ming; Yuan, Fei; Zhou, Xin; Zhang, Zhuoli

2018-06-01

This study aimed to investigate the feasibility of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate visceral adipose tissue (VAT) oxygenation in Zucker diabetic fatty (ZDF) rats and its associations with systemic metaflammation. Five-week-old ZDF rats and Zucker lean (ZL) rats were fed a high-fat diet (HFD) for 18 weeks. A baseline BOLD-MRI scan of perirenal adipose tissue was performed after 8 weeks of HFD feeding, and then the rats were randomized to receive pioglitazone or a vehicle for the following 10 weeks. At sacrifice, BOLD-MRI scan, Hypoxyprobe-1 injection, and circulating T helper 17 (Th17), regulatory T (Treg) cells, and monocyte subtype flow cytometry analysis were performed. HFD feeding led to a significant increase in VAT BOLD-MRI R2* signals (20.14 ± 0.23 per second vs. 21.53 ± 0.20 per second; P = 0.012), an indicator for decreased oxygenation. R2* signal was significantly correlated with VAT pimonidazole adduct-positive area, insulin resistance, Th17 and Treg cells, CD43 + and CD43+ + monocyte subtypes, and VAT macrophage infiltration. Pioglitazone treatment improved the insulin resistance and was associated with a delayed progression of VAT oxygenation. This work demonstrated the feasibility of BOLD-MRI for detecting the VAT oxygenation status in ZDF rats, and the BOLD-MRI signals were associated with insulin resistance and systemic metaflammation in ZDF rats during the development of obesity. © 2018 The Obesity Society.

Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats

PubMed Central

Acevedo, Luz M.; Raya, Ana I.; Martínez-Moreno, Julio M.

2017-01-01

Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats. PMID:28253314

Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats.

PubMed

Acevedo, Luz M; Raya, Ana I; Martínez-Moreno, Julio M; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

2017-01-01

Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats.

Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

NASA Astrophysics Data System (ADS)

Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

2010-04-01

This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p <0.05. Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p <0.05. We conclude that dietary intervention differentially affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

Zonula occludens-1 (ZO-1) is involved in morula to blastocyst transformation in the mouse

PubMed Central

Wang, Hehai; Ding, Tianbing; Brown, Naoko; Yamamoto, Yasutoshi; Prince, Lawrence S.; Reese, Jeff; Paria, B. C.

2008-01-01

It is unknown whether or not tight junction formation plays any role in morula to blastocyst transformation that is associated with development of polarized trophoblast cells and fluid accumulation. Tight junctions are a hallmark of polarized epithelial cells and zonula occludens-1 (ZO-1) is a known key regulator of tight junction formation. Here we show that ZO-1 protein is first expressed during compaction of 8-cell embryos. This stage-specific appearance of ZO-1 suggests its participation in morula to blastocyst transition. Consistent with this idea, we demonstrate that ZO-1 siRNA delivery inside the blastomeres of zona-weakened embryos using electroporation not only knocks down ZO-1 gene and protein expressions, but also inhibits morula to blastocyst transformation in a concentration dependent manner. In addition, ZO-1 inactivation reduced the expression of Cdx2 and Oct-4, but not ZO-2 and F-actin. These results provide the first evidence that ZO-1 is involved in blastocyst formation from the morula by regulating accumulation of fluid and differentiation of nonpolar blastomeres to polar trophoblast cells. PMID:18423437

Effects of antiglucocorticoid RU 486 on development of obesity in obese fa/fa Zucker rats.

PubMed

Langley, S C; York, D A

1990-09-01

The effects of RU 486 (mitepristone), an antagonist of type II glucocorticoid receptors (GR), on the development of obesity in young 5-wk-old obese fa/fa rats has been investigated. After 15 days of treatment, body composition of obese RU 486-treated rats was similar to that of lean-vehicle rats. Analysis of body composition changes showed that RU 486 effectively reversed the obesity. It stopped fat deposition in obese rats but increased protein deposition to the level of lean-vehicle rats. RU 486 prevented the development of hyperphagia and reduced gross energetic efficiency in the obese rats but had little effect on lean rats. Brown adipose tissue mitochondrial GDP binding was increased in obese rats but was reduced in lean rats by RU 486 treatment. RU 486 also reduced the elevated activity of hippocampal glycerophosphate dehydrogenase, a glucocorticoid-responsive enzyme, of obese rats to the level of lean rats. The evidence suggests that abnormal activity of glucocorticoid GR receptors or abnormal cellular responsiveness to corticosterone receptor complexes may be important in the development of obesity in the fa/fa rat.

The tight junction protein ZO-2 and Janus kinase 1 mediate intercellular communications in vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tkachuk, Natalia; Tkachuk, Sergey; Patecki, Margret

2011-07-08

Highlights: {yields} The tight junction protein ZO-2 associates with Jak1 in vascular smooth muscle cells via ZO-2 N-terminal fragment. {yields} Jak1 mediates ZO-2 tyrosine phosphorylation and ZO-2 localization to the sites of homotypic intercellular contacts. {yields} The urokinase receptor uPAR regulates ZO-2/Jak1 functional association. {yields} The ZO-2/Jak1/uPAR signaling complex is required for vascular smooth muscle cells functional network formation. -- Abstract: Recent evidence points to a multifunctional role of ZO-2, the tight junction protein of the MAGUK (membrane-associated guanylate kinase-like) family. Though ZO-2 has been found in cell types lacking tight junction structures, such as vascular smooth muscle cells (VSMC),more » little is known about ZO-2 function in these cells. We provide evidence that ZO-2 mediates specific homotypic cell-to-cell contacts between VSMC. Using mass spectrometry we found that ZO-2 is associated with the non-receptor tyrosine kinase Jak1. By generating specific ZO-2 constructs we further found that the N-terminal fragment of ZO-2 molecule is responsible for this interaction. Adenovirus-based expression of Jak1 inactive mutant demonstrated that Jak1 mediates ZO-2 tyrosine phosphorylation. By means of RNA silencing, expression of Jak1 mutant form and fluorescently labeled ZO-2 fusion protein we further specified that active Jak1, but not Jak1 inactive mutant, mediates ZO-2 localization to the sites of intercellular contacts. We identified the urokinase receptor uPAR as a pre-requisite for these cellular events. Functional requirement of the revealed signaling complex for VSMC network formation was confirmed in experiments using Matrigel and in contraction assay. Our findings imply involvement of the ZO-2 tight junction independent signaling complex containing Jak1 and uPAR in VSMC intercellular communications. This mechanism may contribute to vascular remodeling in occlusive cardiovascular diseases and in

Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and leptin in serum and adipose tissue.

PubMed

Peplow, Philip V

2015-04-01

Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose tissue were collected. Analysis of variance and Duncan's tests showed that the mean leptin in serum was significantly lower and the adiponectin:leptin ratio was significantly higher in Group 2 than in Group 1 (p < 0.05); for Group 4, the serum leptin was significantly higher than it was for Groups 1-3 (p < 0.05), and the adiponectin:leptin ratio was significantly lower than it was for Group 2 (p < 0.05). Similar changes occurred for the leptin levels in the pelvic adipose tissue. In addition, for Group 2, the mean serum insulin: glucose ratio was significantly higher than it was for Group 1 (p < 0.05); for Group 4 the mean serum insulin and insulin: glucose ratio were significantly higher than they were for Groups 1 and 3 (p < 0.05), but not Group 2 (p > 0.05). No significant differences in the serum or the adipose-tissue measurements between Groups 1 and 3 were observed (p > 0.05). Copyright © 2015. Published by Elsevier B.V.

Mixed Effects Modeling Using Stochastic Differential Equations: Illustrated by Pharmacokinetic Data of Nicotinic Acid in Obese Zucker Rats.

PubMed

Leander, Jacob; Almquist, Joachim; Ahlström, Christine; Gabrielsson, Johan; Jirstrand, Mats

2015-05-01

Inclusion of stochastic differential equations in mixed effects models provides means to quantify and distinguish three sources of variability in data. In addition to the two commonly encountered sources, measurement error and interindividual variability, we also consider uncertainty in the dynamical model itself. To this end, we extend the ordinary differential equation setting used in nonlinear mixed effects models to include stochastic differential equations. The approximate population likelihood is derived using the first-order conditional estimation with interaction method and extended Kalman filtering. To illustrate the application of the stochastic differential mixed effects model, two pharmacokinetic models are considered. First, we use a stochastic one-compartmental model with first-order input and nonlinear elimination to generate synthetic data in a simulated study. We show that by using the proposed method, the three sources of variability can be successfully separated. If the stochastic part is neglected, the parameter estimates become biased, and the measurement error variance is significantly overestimated. Second, we consider an extension to a stochastic pharmacokinetic model in a preclinical study of nicotinic acid kinetics in obese Zucker rats. The parameter estimates are compared between a deterministic and a stochastic NiAc disposition model, respectively. Discrepancies between model predictions and observations, previously described as measurement noise only, are now separated into a comparatively lower level of measurement noise and a significant uncertainty in model dynamics. These examples demonstrate that stochastic differential mixed effects models are useful tools for identifying incomplete or inaccurate model dynamics and for reducing potential bias in parameter estimates due to such model deficiencies.

Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues.

PubMed

Zhou, Zejun; Zhang, Lumin; Ding, Miao; Luo, Zhenwu; Yuan, Shao; Bansal, Meena B; Gilkeson, Gary; Lang, Ren; Jiang, Wei

2017-10-01

Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. Copyright © 2017 Elsevier Inc. All rights reserved.

Contrasting apoptotic responses of conjugated linoleic acid in the liver of obese Zucker rats fed palm oil or ovine fat.

PubMed

Lopes, Paula A; Martins, Susana V; Viana, Ricardo S J; Ramalho, Rita M; Alfaia, Cristina M; Pinho, Mário S; Jerónimo, Eliana; Bessa, Rui J B; Castro, Matilde F; Rodrigues, Cecília M P; Prates, José A M

2011-08-01

We hypothesized that reducing weight properties of conjugated linoleic acid (CLA) are due to adipocyte apoptosis and that CLA differentially modulates the apoptotic responses in hepatic lipotoxicity from rats fed saturated fat diets. Obese Zucker rats were fed atherogenic diets (2%w/w of cholesterol) formulated with high (15%w/w) saturated fat, from vegetable or animal origin, supplemented or not with 1% of a mixture (1:1) of cis-9, trans-11 and trans-10, cis-12 CLA isomers for 14 weeks. CLA induced no changes on retroperitoneal fat depot weight, which was in line with similar levels of apoptosis. Interestingly, CLA had a contrasting effect on cell death in the liver according to the dietary fat. CLA increased hepatocyte apoptosis, associated with upregulation of Fas protein in rats fed palm oil, compared to rats receiving palm oil alone. However, rats fed ovine fat alone displayed the highest levels of hepatic cell death, which were decreased in rats fed ovine fat plus CLA. This reducing effect of CLA was related to positively restoring endoplasmic reticulum (ER) ATF-6α, BiP and CHOP protein levels and increasing phosphorylated c-Jun NH(2)-terminal kinase (JNK) and c-Jun, thus suggesting an adaptive response of cell survival. These findings reinforce the role of CLA as regulator of apoptosis in the liver. Moreover, the dietary fat composition is a key factor in activation of apoptosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rimonabant's reductive effects on high densities of food reinforcement, but not palatability, in lean and obese Zucker rats.

PubMed

Buckley, Jessica L; Rasmussen, Erin B

2014-05-01

Cannabinoid antagonists purportedly have greater effects in reducing the intake of highly palatable food compared to less palatable food. However, this assertion is based on free-feeding studies in which the amount of palatable food eaten under baseline conditions is often confounded with other variables, such as unequal access to both food options and differences in qualitative features of the foods. We attempted to reduce these confounds by using a model of choice that programmed the delivery rates of sucrose and carrot-flavored pellets. Lever pressing of ten lean (Fa/Fa or Fa/fa) and ten obese (fa/fa) Zucker rats was placed under three conditions in which programmed ratios for food pellets on two levers were 5:1, 1:1, and 1:5. In phase 1, responses on the two levers produced one type of pellet (sucrose or carrot); in phase 2, responses on one lever produced sucrose pellets and on the other lever produced carrot pellets. After responses stabilized under each food ratio, acute doses of rimonabant (0, 3, and 10 mg/kg) were administered before experimental sessions. The number of reinforcers and responses earned per session under each ratio and from each lever was compared. Rimonabant reduced reinforcers in 1:5 and 5:1 food ratios in phase 1, and across all ratios in phase 2. Rimonabant reduced sucrose and carrot-flavored pellet consumption similarly; rimonabant did not affect bias toward sucrose, but increased sensitivity to amount differences in lean rats. This suggests that relative amount of food, not palatability, may be an important behavioral mechanism in the effects of rimonabant.

Hepatic immunohistochemical localization of the tight junction protein ZO-1 in rat models of cholestasis.

PubMed Central

Anderson, J. M.; Glade, J. L.; Stevenson, B. R.; Boyer, J. L.; Mooseker, M. S.

1989-01-01

Structural alterations in hepatocyte tight junctions accompanying cholestasis were investigated using immunolocalization of ZO-1, the first known protein component of the tight junction. Disruption in the paracellular barrier function of the tight junction has been proposed to allow reflux of bile into the blood. Cholestasis was induced in 210 to 235 g male Sprague-Dawley rats either by five consecutive daily subcutaneous injections of 17-alpha-ethinyl estradiol (0.5 mg/kg/d in propylene glycol) or ligation of the common bile duct for 72 hours. The structural organization of the tight junction was assessed in each model by indirect immunofluorescent and immunoperoxidase staining for ZO-1 on frozen sections of liver and compared with controls. In control, sham-operated, and estradiol-injected animals, ZO-1 localizes in a uniform continuous manner along the margins of the canaliculi. In contrast, bile duct ligation results in the appearance of numerous discontinuities in ZO-1 staining accompanied by dilation or collapse of the lumenal space. Tissue content of the ZO-1 protein, as determined by quantitative immunoblotting, was unaffected in either cholestatic model compared with controls. These findings indicate that the molecular organization of the tight junction can be assessed from immunostaining patterns of ZO-1 in frozen sections of cholestatic livers. Under these experimental conditions, the organization of the tight junction at the level of the ZO-1 protein is altered by bile duct obstruction but not by ethinyl estradiol. Images Figure 1 Figure 2 PMID:2719075

Plasma endocannabinoid levels in lean, overweight and obese humans: relationships with intestinal permeability markers, inflammation and incretin secretion.

PubMed

Little, Tanya J; Cvijanovic, Nada; DiPatrizio, Nicholas V; Argueta, Donovan A; Rayner, Christopher K; Feinle-Bisset, Christine; Young, Richard L

2018-02-13

Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion. 20 lean, 18 overweight and 19 obese participants underwent intraduodenal Intralipid® infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumour necrosis factor-α (TNF-α), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and toll-like receptor-4 (TLR4) (RT-PCR), were assessed. Fasting plasma AEA was increased in obese, compared with lean and overweight (P<0.05), with no effect of BMI group or ID lipid infusion on plasma 2-AG or OEA. Duodenal expression of IAP and ZO-1 was reduced in obese, compared with lean (P<0.05), and these levels related negatively to plasma AEA (P<0.05). The iAUC for AEA was positively related to iAUC GIP (r=0.384, P=0.005). Obese individuals have increased plasma AEA and decreased duodenal expression of ZO-1 and IAP, in comparison to lean and overweight. The relationships between plasma AEA with duodenal ZO-1 and IAP, and GIP, suggest that altered endocannabinoid signalling may contribute to changes in intestinal permeability, inflammation and incretin release in human obesity.

Rimonabant’s Reductive Effects on High Densities of Food Reinforcement, but not Palatability, in Lean and Obese Zucker Rats

PubMed Central

Buckley, Jessica Lynn; Rasmussen, Erin B.

2014-01-01

Rationale Cannabinoid antagonists purportedly have greater effects in reducing the intake of highly palatable food compared to less palatable food. However, this assertion is based on free-feeding studies in which the amount of palatable food eaten under baseline conditions is often confounded with other variables, such as unequal access to both food options and differences in qualitative features of the foods. Objective We attempted to reduce these confounds by using a model of choice that programmed the delivery rates of sucrose and carrot-flavored pellets. Methods Lever-pressing of ten lean (Fa/Fa or Fa/fa) and ten obese (fa/fa) Zucker rats was placed under three conditions in which programmed ratios for food pellets on two levers were 5:1, 1:1, and 1:5. In Phase 1, responses on the two levers produced one type of pellet (sucrose or carrot); in Phase 2, responses on one lever produced sucrose pellets and on the other lever produced carrot pellets. After responses stabilized under each food ratio, acute doses of rimonabant (0, 3, and 10 mg/kg) were administered before experimental sessions. The number of reinforcers and responses earned per session under each ratio and from each lever was compared. Results and Conclusions Rimonabant reduced reinforcers in 1:5 and 5:1 food ratios in Phase 1, and across all ratios in Phase 2. Rimonabant reduced sucrose and carrot-flavored pellet consumption similarly; rimonabant did not affect bias toward sucrose, but increased sensitivity to amount differences in lean rats. This suggests that relative amount of food, not palatability, may be an important behavioral mechanism in the effects of rimonabant. PMID:24398820

Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats.

PubMed

Kubota, Masatoshi; Watanabe, Reiko; Yamaguchi, Miki; Hosojima, Michihiro; Saito, Akihiko; Fujii, Mikio; Fujimura, Shinobu; Kadowaki, Motoni

2016-10-01

We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (P<0·05). Compared with C in the liver, REP prevented lipid accumulation (total lipid, TAG and total cholesterol, P<0·01). Liver metabolome analysis indicated that levels of metabolites associated with glycolysis, the pentose phosphate pathway and carnitine metabolism were significantly greater in the REP group than in the C group (P<0·05), suggesting activation of both glucose catabolism and fatty acid oxidation. The metabolite increases promoted by REP may contribute to suppression of liver lipid accumulation. Urinary excretion of albumin and N-acetyl-β-d-glucosaminidase was significantly reduced in rats fed REP for 8 weeks (P<0·01). In addition, there was a distinct suppression of mesangial matrix expansion and glomerular hypertrophy in response to REP (P<0·01). Thus, REP had preventive effects on obese diabetes, fatty liver and diabetic nephropathy.

Changes in alanine turnover rate due to nutritional and genetic obesity in the rat.

PubMed

Yebras, M; Salvadó, J; Arola, L; Remesar, X; Segués, T

1994-08-01

The changes in alanine turnover were determined in Zucker rats, which were either genetically obese (fa/fa) or rendered obese by dietary treatment (cafeteria fed). The whole body rate of alanine turnover was higher in genetically obese rats than in rats in which obesity was induced by diet (cafeteria). This is possibly due to variations in the rate of the amino acid incorporation into proteins, since the rate of whole body alanine degradation is the same for both groups. Thus, the different pattern followed by alanine turnover rate in these types of obese animals reflects the differences in the nitrogen economy of these animals, pointing to a higher alanine utilization in the genetically obese animals and a conservative management of alanine in the cafeteria-fed animals.

A cafeteria diet triggers intestinal inflammation and oxidative stress in obese rats.

PubMed

Gil-Cardoso, K; Ginés, I; Pinent, M; Ardévol, A; Terra, X; Blay, M

2017-01-01

The gastrointestinal alterations associated with the consumption of an obesogenic diet, such as inflammation, permeability impairment and oxidative stress, have been poorly explored in both diet-induced obesity (DIO) and genetic obesity. The aim of the present study was to examine the impact of an obesogenic diet on the gut health status of DIO rats in comparison with the Zucker (fa/fa) rat leptin receptor-deficient model of genetic obesity over time. For this purpose, female Wistar rats (n 48) were administered a standard or a cafeteria diet (CAF diet) for 12, 14·5 or 17 weeks and were compared with fa/fa Zucker rats fed a standard diet for 10 weeks. Morphometric variables, plasma biochemical parameters, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) levels in the ileum were assessed, as well as the expressions of proinflammatory genes (TNF-α and inducible nitric oxide synthase (iNOS)) and intestinal permeability genes (zonula occludens-1, claudin-1 and occludin). Both the nutritional model and the genetic obesity model showed increased body weight and metabolic alterations at the final time point. An increase in intestinal ROS production and MPO activity was observed in the gastrointestinal tracts of rats fed a CAF diet but not in the genetic obesity model. TNF-α was overexpressed in the ileum of both CAF diet and fa/fa groups, and ileal inflammation was associated with the degree of obesity and metabolic alterations. Interestingly, the 17-week CAF group and the fa/fa rats exhibited alterations in the expressions of permeability genes. Relevantly, in the hyperlipidic refined sugar diet model of obesity, the responses to chronic energy overload led to time-dependent increases in gut inflammation and oxidative stress.

Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats.

PubMed

Tan, Yi; Kim, Jane; Cheng, Jing; Ong, Madeleine; Lao, Wei-Guo; Jin, Xing-Liang; Lin, Yi-Guang; Xiao, Linda; Zhu, Xue-Qiong; Qu, Xian-Qin

2017-06-07

To investigate protective effects and molecular mechanisms of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats. Male ZF rats were fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1c (SREBP1c). Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain (10.1%, P = 0.052) and significantly lowered visceral fat (31.0%, P < 0.01). Compared with ZF-controls, GTP treatment significantly reduced fasting serum insulin, glucose and lipids levels. Reduction in serum ALT and AST levels (both P < 0.01) were observed in GTP-treated ZF rats. GTP treatment also attenuated the elevated TNFα and IL-6 in the circulation. The increased hepatic TG accumulation and cytoplasmic lipid droplet were attenuated by GTP treatment, associated with significantly increased expression of AMPK-Thr172 ( P < 0.05) and phosphorylated ACC and SREBP1c (both P < 0.05), indicating diminished hepatic lipogenesis and triglycerides out flux from liver in GTP treated rats. The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.

The ZO-1–associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density

PubMed Central

Balda, Maria S.; Garrett, Michelle D.; Matter, Karl

2003-01-01

Epithelial tight junctions regulate paracellular permeability, restrict apical/basolateral intramembrane diffusion of lipids, and have been proposed to participate in the control of epithelial cell proliferation and differentiation. Previously, we have identified ZO-1–associated nucleic acid binding proteins (ZONAB), a Y-box transcription factor whose nuclear localization and transcriptional activity is regulated by the tight junction–associated candidate tumor suppressor ZO-1. Now, we found that reduction of ZONAB expression using an antisense approach or by RNA interference strongly reduced proliferation of MDCK cells. Transfection of wild-type or ZONAB-binding fragments of ZO-1 reduced proliferation as well as nuclear ZONAB pools, indicating that promotion of proliferation by ZONAB requires its nuclear accumulation. Overexpression of ZONAB resulted in increased cell density in mature monolayers, and depletion of ZONAB or overexpression of ZO-1 reduced cell density. ZONAB was found to associate with cell division kinase (CDK) 4, and reduction of nuclear ZONAB levels resulted in reduced nuclear CDK4. Thus, our data indicate that tight junctions can regulate epithelial cell proliferation and cell density via a ZONAB/ZO-1–based pathway. Although this regulatory process may also involve regulation of transcription by ZONAB, our data suggest that one mechanism by which ZONAB and ZO-1 influence proliferation is by regulating the nuclear accumulation of CDK4. PMID:12566432

Voluntary running exercise prevents β-cell failure in susceptible islets of the Zucker diabetic fatty rat.

PubMed

Delghingaro-Augusto, Viviane; Décary, Simon; Peyot, Marie-Line; Latour, Martin G; Lamontagne, Julien; Paradis-Isler, Nicolas; Lacharité-Lemieux, Marianne; Akakpo, Huguette; Birot, Olivier; Nolan, Christopher J; Prentki, Marc; Bergeron, Raynald

2012-01-15

Physical activity improves glycemic control in type 2 diabetes (T2D), but its contribution to preserving β-cell function is uncertain. We evaluated the role of physical activity on β-cell secretory function and glycerolipid/fatty acid (GL/FA) cycling in male Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats engaged in voluntary running for 6 wk (ZDF-A). Inactive Zucker lean and ZDF (ZDF-I) rats served as controls. ZDF-I rats displayed progressive hyperglycemia with β-cell failure evidenced by falling insulinemia and reduced insulin secretion to oral glucose. Isolated ZDF-I rat islets showed reduced glucose-stimulated insulin secretion expressed per islet and per islet protein. They were also characterized by loss of the glucose regulation of fatty acid oxidation and GL/FA cycling, reduced mRNA expression of key β-cell genes, and severe reduction of insulin stores. Physical activity prevented diabetes in ZDF rats through sustaining β-cell compensation to insulin resistance shown in vivo and in vitro. Surprisingly, ZDF-A islets had persistent defects in fatty acid oxidation, GL/FA cycling, and β-cell gene expression. ZDF-A islets, however, had preserved islet insulin mRNA and insulin stores compared with ZDF-I rats. Physical activity did not prevent hyperphagia, dyslipidemia, or obesity in ZDF rats. In conclusion, islets of ZDF rats have a susceptibility to failure that is possibly due to altered β-cell fatty acid metabolism. Depletion of pancreatic islet insulin stores is a major contributor to islet failure in this T2D model, preventable by physical activity.

Methodological evaluation of indirect calorimetry data in lean and obese rats.

PubMed

Rafecas, I; Esteve, M; Fernández-López, J A; Remesar, X; Alemany, M

1993-11-01

1. The applicability of current indirect calorimetry formulae to the study of energy and substrate balances on obese rats has been evaluated. The energy consumption of series of 60-day rats of Wistar, lean and obese Zucker stock were studied by means of direct and indirect calorimetry, and by establishing their energy balance through measurement of food intake and retention. Calorimetric studies encompassed a 24 h period, with gas and heat output measurements every 2 or 5 min, respectively, for direct and indirect calorimetry. 2. The analysis of fat composition (diet, whole rat, and synthesized and oxidized fat) showed only small variations that had only a limited effect on the overall energy equation parameters. 3. A gap in the nitrogen balance, which represents a urinary N excretion lower than the actual protein oxidized, resulted in significant deviations in the estimation of carbohydrate and lipid oxidized when using the equations currently available for indirect calorimetry. 4. Analysis of the amino acid composition of diet and rat protein as well as of the portion actually oxidized, and correcting for the nitrogen gap allowed the establishment of a set of equations that gave better coincidence of the calculated data with the measured substrate balance. 5. The measured heat output of all rats was lower than the estimated values calculated by means of either indirect calorimetry of direct energy balance measurement; the difference corresponded to the energy lost in water evaporation, and was in the range of one-fifth of total energy produced in the three rat stocks. 6. Wistar rats showed a biphasic circadian rhythm of substrate utilization, with alternate lipid synthesis/degradation that reversed that of carbohydrate, concordant with nocturnal feeding habits. Zucker rats did not show this rhythm; obese rats synthesized large amounts of fat during most of the light period, consuming fat at the end of the dark period, which suggests more diurnal feeding habits

ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells.

PubMed

Zhang, Hu; Zhang, Shuhong; Zhang, Jilin; Liu, Dongxin; Wei, Jiayi; Fang, Wengang; Zhao, Weidong; Chen, Yuhua; Shang, Deshu

2018-05-01

The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear. Herein, we found that the erythroblast transformation-specific (ETS) transcription factor ERG cooperated with the proto-oncogene protein c-MYC in regulation of ZO-1 transcription in brain microvascular endothelial cells (BMECs). The ERG expression was suppressed by miR-96 which was increased by GM-CSF through the phosphoinositide-3 kinase (PI3K)/Akt pathway. Inhibition of miR-96 prevented ZO-1 down-regulation induced by GM-CSF both in vitro and in vivo. Our results revealed the mechanism of ZO-1 expression reduced by GM-CSF, and provided a potential target, miR-96, which could block ZO-1 down-regulation caused by GM-CSF in BMECs.

IVGTT-based simple assessment of glucose tolerance in the Zucker fatty rat: Validation against minimal models.

PubMed

Morettini, Micaela; Faelli, Emanuela; Perasso, Luisa; Fioretti, Sandro; Burattini, Laura; Ruggeri, Piero; Di Nardo, Francesco

2017-01-01

For the assessment of glucose tolerance from IVGTT data in Zucker rat, minimal model methodology is reliable but time- and money-consuming. This study aimed to validate for the first time in Zucker rat, simple surrogate indexes of insulin sensitivity and secretion against the glucose-minimal-model insulin sensitivity index (SI) and against first- (Φ1) and second-phase (Φ2) β-cell responsiveness indexes provided by C-peptide minimal model. Validation of the surrogate insulin sensitivity index (ISI) and of two sets of coupled insulin-based indexes for insulin secretion, differing from the cut-off point between phases (FPIR3-SPIR3, t = 3 min and FPIR5-SPIR5, t = 5 min), was carried out in a population of ten Zucker fatty rats (ZFR) and ten Zucker lean rats (ZLR). Considering the whole rat population (ZLR+ZFR), ISI showed a significant strong correlation with SI (Spearman's correlation coefficient, r = 0.88; P<0.001). Both FPIR3 and FPIR5 showed a significant (P<0.001) strong correlation with Φ1 (r = 0.76 and r = 0.75, respectively). Both SPIR3 and SPIR5 showed a significant (P<0.001) strong correlation with Φ2 (r = 0.85 and r = 0.83, respectively). ISI is able to detect (P<0.001) the well-recognized reduction in insulin sensitivity in ZFRs, compared to ZLRs. The insulin-based indexes of insulin secretion are able to detect in ZFRs (P<0.001) the compensatory increase of first- and second-phase secretion, associated to the insulin-resistant state. The ability of the surrogate indexes in describing glucose tolerance in the ZFRs was confirmed by the Disposition Index analysis. The model-based validation performed in the present study supports the utilization of low-cost, insulin-based indexes for the assessment of glucose tolerance in Zucker rat, reliable animal model of human metabolic syndrome.

The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression

PubMed Central

Balda, Maria S.; Matter, Karl

2000-01-01

Epithelial tight junctions regulate paracellular diffusion and restrict the intermixing of apical and basolateral plasma membrane components. We now identify a Y-box transcription factor, ZONAB (ZO-1-associated nucleic acid-binding protein), that binds to the SH3 domain of ZO-1, a submembrane protein of tight junctions. ZONAB localizes to the nucleus and at tight junctions, and binds to sequences of specific promoters containing an inverted CCAAT box. In reporter assays, ZONAB and ZO-1 functionally interact in the regulation of the ErbB-2 promoter in a cell density-dependent manner. In stably transfected overexpressing cells, ZO-1 and ZONAB control expression of endogenous ErbB-2 and function in the regulation of paracellular permeability. These data indicate that tight junctions directly participate in the control of gene expression and suggest that they function in the regulation of epithelial cell differentiation. PMID:10790369

Involvement of the interaction of afadin with ZO-1 in the formation of tight junctions in Madin-Darby canine kidney cells.

PubMed

Ooshio, Takako; Kobayashi, Reiko; Ikeda, Wataru; Miyata, Muneaki; Fukumoto, Yuri; Matsuzawa, Naomi; Ogita, Hisakazu; Takai, Yoshimi

2010-02-12

Tight junctions (TJs) and adherens junctions (AJs) are major junctional apparatuses in epithelial cells. Claudins and junctional adhesion molecules (JAMs) are major cell adhesion molecules (CAMs) at TJs, whereas cadherins and nectins are major CAMs at AJs. Claudins and JAMs are associated with ZO proteins, whereas cadherins are associated with beta- and alpha-catenins, and nectins are associated with afadin. We previously showed that nectins first form cell-cell adhesions where the cadherin-catenin complex is recruited to form AJs, followed by the recruitment of the JAM-ZO and claudin-ZO complexes to the apical side of AJs to form TJs. It is not fully understood how TJ components are recruited to the apical side of AJs. We studied the roles of afadin and ZO-1 in the formation of TJs in Madin-Darby canine kidney (MDCK) cells. Before the formation of TJs, ZO-1 interacted with afadin through the two proline-rich regions of afadin and the SH3 domain of ZO-1. During and after the formation of TJs, ZO-1 dissociated from afadin and associated with JAM-A. Knockdown of afadin impaired the formation of both AJs and TJs in MDCK cells, whereas knockdown of ZO-1 impaired the formation of TJs, but not AJs. Re-expression of full-length afadin restored the formation of both AJs and TJs in afadin-knockdown MDCK cells, whereas re-expression of afadin-DeltaPR1-2, which is incapable of binding to ZO-1, restored the formation of AJs, but not TJs. These results indicate that the transient interaction of afadin with ZO-1 is necessary for the formation of TJs in MDCK cells.

Involvement of the Interaction of Afadin with ZO-1 in the Formation of Tight Junctions in Madin-Darby Canine Kidney Cells*

PubMed Central

Ooshio, Takako; Kobayashi, Reiko; Ikeda, Wataru; Miyata, Muneaki; Fukumoto, Yuri; Matsuzawa, Naomi; Ogita, Hisakazu; Takai, Yoshimi

2010-01-01

Tight junctions (TJs) and adherens junctions (AJs) are major junctional apparatuses in epithelial cells. Claudins and junctional adhesion molecules (JAMs) are major cell adhesion molecules (CAMs) at TJs, whereas cadherins and nectins are major CAMs at AJs. Claudins and JAMs are associated with ZO proteins, whereas cadherins are associated with β- and α-catenins, and nectins are associated with afadin. We previously showed that nectins first form cell-cell adhesions where the cadherin-catenin complex is recruited to form AJs, followed by the recruitment of the JAM-ZO and claudin-ZO complexes to the apical side of AJs to form TJs. It is not fully understood how TJ components are recruited to the apical side of AJs. We studied the roles of afadin and ZO-1 in the formation of TJs in Madin-Darby canine kidney (MDCK) cells. Before the formation of TJs, ZO-1 interacted with afadin through the two proline-rich regions of afadin and the SH3 domain of ZO-1. During and after the formation of TJs, ZO-1 dissociated from afadin and associated with JAM-A. Knockdown of afadin impaired the formation of both AJs and TJs in MDCK cells, whereas knockdown of ZO-1 impaired the formation of TJs, but not AJs. Re-expression of full-length afadin restored the formation of both AJs and TJs in afadin-knockdown MDCK cells, whereas re-expression of afadin-ΔPR1–2, which is incapable of binding to ZO-1, restored the formation of AJs, but not TJs. These results indicate that the transient interaction of afadin with ZO-1 is necessary for the formation of TJs in MDCK cells. PMID:20008323

The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB.

PubMed

Tsapara, Anna; Matter, Karl; Balda, Maria S

2006-03-01

The tight junction adaptor protein ZO-1 regulates intracellular signaling and cell proliferation. Its Src homology 3 (SH3) domain is required for the regulation of proliferation and binds to the Y-box transcription factor ZO-1-associated nucleic acid binding protein (ZONAB). Binding of ZO-1 to ZONAB results in cytoplasmic sequestration and hence inhibition of ZONAB's transcriptional activity. Here, we identify a new binding partner of the SH3 domain that modulates ZO-1-ZONAB signaling. Expression screening of a cDNA library with a fusion protein containing the SH3 domain yielded a cDNA coding for Apg-2, a member of the heat-shock protein 110 (Hsp 110) subfamily of Hsp70 heat-shock proteins, which is overexpressed in carcinomas. Regulated depletion of Apg-2 in Madin-Darby canine kidney cells inhibits G(1)/S phase progression. Apg-2 coimmunoprecipitates with ZO-1 and partially localizes to intercellular junctions. Junctional recruitment and coimmunoprecipitation with ZO-1 are stimulated by heat shock. Apg-2 competes with ZONAB for binding to the SH3 domain in vitro and regulates ZONAB's transcriptional activity in reporter gene assays. Our data hence support a model in which Apg-2 regulates ZONAB function by competing for binding to the SH3 domain of ZO-1 and suggest that Apg-2 functions as a regulator of ZO-1-ZONAB signaling in epithelial cells in response to cellular stress.

The Heat-Shock Protein Apg-2 Binds to the Tight Junction Protein ZO-1 and Regulates Transcriptional Activity of ZONAB

PubMed Central

Tsapara, Anna; Matter, Karl; Balda, Maria S.

2006-01-01

The tight junction adaptor protein ZO-1 regulates intracellular signaling and cell proliferation. Its Src homology 3 (SH3) domain is required for the regulation of proliferation and binds to the Y-box transcription factor ZO-1-associated nucleic acid binding protein (ZONAB). Binding of ZO-1 to ZONAB results in cytoplasmic sequestration and hence inhibition of ZONAB's transcriptional activity. Here, we identify a new binding partner of the SH3 domain that modulates ZO-1–ZONAB signaling. Expression screening of a cDNA library with a fusion protein containing the SH3 domain yielded a cDNA coding for Apg-2, a member of the heat-shock protein 110 (Hsp 110) subfamily of Hsp70 heat-shock proteins, which is overexpressed in carcinomas. Regulated depletion of Apg-2 in Madin-Darby canine kidney cells inhibits G1/S phase progression. Apg-2 coimmunoprecipitates with ZO-1 and partially localizes to intercellular junctions. Junctional recruitment and coimmunoprecipitation with ZO-1 are stimulated by heat shock. Apg-2 competes with ZONAB for binding to the SH3 domain in vitro and regulates ZONAB's transcriptional activity in reporter gene assays. Our data hence support a model in which Apg-2 regulates ZONAB function by competing for binding to the SH3 domain of ZO-1 and suggest that Apg-2 functions as a regulator of ZO-1–ZONAB signaling in epithelial cells in response to cellular stress. PMID:16407410

Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

PubMed

Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

2017-12-01

Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

Transgenic animal model for studying the mechanism of obesity-associated stress urinary incontinence.

PubMed

Wang, Lin; Lin, Guiting; Lee, Yung-Chin; Reed-Maldonado, Amanda B; Sanford, Melissa T; Wang, Guifang; Li, Huixi; Banie, Lia; Xin, Zhengcheng; Lue, Tom F

2017-02-01

To study and compare the function and structure of the urethral sphincter in female Zucker lean (ZL) and Zucker fatty (ZF) rats and to assess the viability of ZF fats as a model for female obesity-associated stress urinary incontinence (SUI). Two study arms were created: a ZL arm including 16-week-old female ZL rats (ZUC-Lepr fa 186; n = 12) and a ZF arm including 16-week-old female ZF rats (ZUC-Lepr fa 185; n = 12). I.p. insulin tolerance testing was carried out before functional study. Metabolic cages, conscious cystometry and leak point pressure (LPP) assessments were conducted. Urethral tissues were harvested for immunofluorescence staining to check intramyocellular lipid (IMCL) and sphincter muscle (smooth muscle and striated muscle) composition. The ZF rats had insulin resistance, a greater voiding frequency and lower LPP compared with ZL rats (P < 0.05), with more IMCL deposition localized in the urethral striated muscle fibres of the ZF rats (P < 0.05). The thickness of the striated muscle layer and the ratio of striated muscle to smooth muscle were lower in ZF than in ZL rats. Obesity impairs urethral sphincter function via IMCL deposition and leads to atrophy and distortion of urethral striated muscle. The ZF rats could be a consistent and reliable animal model in which to study obesity-associated SUI. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Effects of interval aerobic training combined with strength exercise on body composition, glycaemic and lipid profile and aerobic capacity of obese rats.

PubMed

Coll-Risco, Irene; Aparicio, Virginia A; Nebot, Elena; Camiletti-Moirón, Daniel; Martínez, Rosario; Kapravelou, Garyfallia; López-Jurado, María; Porres, Jesús M; Aranda, Pilar

2016-08-01

The purpose of this study was to investigate the effects of interval aerobic training combined with strength exercise in the same training session on body composition, and glycaemic and lipid profile in obese rats. Sixteen lean Zucker rats and sixteen obese Zucker rats were randomly divided into exercise and sedentary subgroups (4 groups, n = 8). Exercise consisted of interval aerobic training combined with strength exercise in the same training session. The animals trained 60 min/day, 5 days/week for 8 weeks. Body composition, lipid and glycaemic profiles and inflammatory markers were assessed. Results showed that fat mass was reduced in both lean and obese rats following the exercise training (effect size (95% confidence interval (CI)) = 1.8 (0.5-3.0)). Plasma low-density lipoprotein-cholesterol and fasting glucose were lower in the exercise compared to the sedentary groups (d = 2.0 (0.7-3.2) and 1.8 (0.5-3.0), respectively). Plasma insulin was reduced in exercise compared to sedentary groups (d = 2.1 (0.8-3.4)). Some exercise × phenotype interactions showed that the highest decreases in insulin, homeostatic model assessment-insulin resistance, fasting and postprandial glucose were observed in the obese + exercise group (all, P < 0.01). The findings of this study suggest that interval aerobic training combined with strength exercise would improve body composition, and lipid and glycaemic profiles, especially in obese rats.

Effect of obesity and exercise on the expression of the novel myokines, Myonectin and Fibronectin type III domain containing 5

PubMed Central

Mart, Ryan; Bond, Cherie E.

2014-01-01

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, Myonectin and Fibronectin type III domain containing 5 (FNDC5), the precursor for Irisin. Methods. We performed immunoblot analysis and quantitative real-time PCR analysis of Myonectin and FNDC5 in the diaphragm muscles of obese Zucker rat (OZR) and lean Zucker rat (LZR) with 9 weeks of aerobic training on a motorized treadmill. Results. We show that myonectin gene expression is increased in the OZR model of obesity and decreases with exercise in both lean and obese Zucker rats. Conversely, myonectin protein concentration was elevated with exercise. Similarly, FNDC5 mRNA levels are significantly higher in the OZR, however exercise training had no effect on the expression level of FNDC5 in either the LZR or OZR. We did not observe any difference in muscle protein content of Irisin with obesity or exercise. Conclusion. Our data shows that exercise training does not increase either FNDC5 or myonectin gene expression, indicating that increased transcriptional regulation of these myokines is not induced by exercise. However, our data also indicates a yet to be explored disconnect between myonectin gene expression and protein content. Further, this report highlights the importance of verifying reference genes when completing gene expression analysis. We found that many commonly used reference genes varied significantly by obesity and

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol.

PubMed

Toyoda, Takeshi; Cho, Young-Man; Akagi, Jun-Ichi; Mizuta, Yasuko; Matsushita, Kohei; Nishikawa, Akiyoshi; Imaida, Katsumi; Ogawa, Kumiko

2017-01-01

3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in high-risk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1.

PubMed

Hou, Qiuke; Huang, Yongquan; Zhu, Shuilian; Li, Peiwu; Chen, Xinlin; Hou, Zhengkun; Liu, Fengbin

2017-01-01

Irritable bowel syndrome with diarrhoea (IBS-D) is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs) are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i) identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii) verify in vitro whether occludin (OCLN) and zonula occludens 1 (ZO1/TJP1) were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii) determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs) and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further studies confirmed that OCLN and ZO1 were direct

Obesity-related pulmonary arterial hypertension in rats correlates with increased circulating inflammatory cytokines and lipids and with oxidant damage in the arterial wall but not with hypoxia

PubMed Central

Irwin, David C.; Garat, Chrystelle V.; Crossno, Joseph T.; MacLean, Paul S.; Sullivan, Timothy M.; Erickson, Paul F.; Jackman, Matthew R.; Harral, Julie W.; Reusch, Jane E. B.

2014-01-01

Abstract Obesity is causally linked to a number of comorbidities, including cardiovascular disease, diabetes, renal dysfunction, and cancer. Obesity has also been linked to pulmonary disorders, including pulmonary arterial hypertension (PAH). It was long believed that obesity-related PAH was the result of hypoventilation and hypoxia due to the increased mechanical load of excess body fat. However, in recent years it has been proposed that the metabolic and inflammatory disturbances of obesity may also play a role in the development of PAH. To determine whether PAH develops in obese rats in the absence of hypoxia, we assessed pulmonary hemodynamics and pulmonary artery (PA) structure in the diet-resistant/diet-induced obesity (DR/DIO) and Zucker lean/fatty rat models. We found that high-fat feeding (DR/DIO) or overfeeding (Zucker) elicited PA remodeling, neomuscularization of distal arterioles, and elevated PA pressure, accompanied by right ventricular (RV) hypertrophy. PA thickening and distal neomuscularization were also observed in DIO rats on a low-fat diet. No evidence of hypoventilation or chronic hypoxia was detected in either model, nor was there a correlation between blood glucose or insulin levels and PAH. However, circulating inflammatory cytokine levels were increased with high-fat feeding or calorie overload, and hyperlipidemia and oxidant damage in the PA wall correlated with PAH in the DR/DIO model. We conclude that hyperlipidemia and peripheral inflammation correlate with the development of PAH in obese subjects. Obesity-related inflammation may predispose to PAH even in the absence of hypoxia. PMID:25610600

Defective calcium inactivation causes long QT in obese insulin-resistant rat.

PubMed

Lin, Yen-Chang; Huang, Jianying; Kan, Hong; Castranova, Vincent; Frisbee, Jefferson C; Yu, Han-Gang

2012-02-15

The majority of diabetic patients who are overweight or obese die of heart disease. We suspect that the obesity-induced insulin resistance may lead to abnormal cardiac electrophysiology. We tested this hypothesis by studying an obese insulin-resistant rat model, the obese Zucker rat (OZR). Compared with the age-matched control, lean Zucker rat (LZR), OZR of 16-17 wk old exhibited an increase in QTc interval, action potential duration, and cell capacitance. Furthermore, the L-type calcium current (I(CaL)) in OZR exhibited defective inactivation and lost the complete inactivation back to the closed state, leading to increased Ca(2+) influx. The current density of I(CaL) was reduced in OZR, whereas the threshold activation and the current-voltage relationship of I(CaL) were not significantly altered. L-type Ba(2+) current (I(BaL)) in OZR also exhibited defective inactivation, and steady-state inactivation was not significantly altered. However, the current-voltage relationship and activation threshold of I(BaL) in OZR exhibited a depolarized shift compared with LZR. The total and membrane protein expression levels of Cav1.2 [pore-forming subunit of L-type calcium channels (LTCC)], but not the insulin receptors, were decreased in OZR. The insulin receptor was found to be associated with the Cav1.2, which was weakened in OZR. The total protein expression of calmodulin was reduced, but that of Cavβ2 subunit was not altered in OZR. Together, these results suggested that the 16- to 17-wk-old OZR has 1) developed cardiac hypertrophy, 2) exhibited altered electrophysiology manifested by the prolonged QTc interval, 3) increased duration of action potential in isolated ventricular myocytes, 4) defective inactivation of I(CaL) and I(BaL), 5) weakened the association of LTCC with the insulin receptor, and 6) decreased protein expression of Cav1.2 and calmodulin. These results also provided mechanistic insights into a remodeled cardiac electrophysiology under the condition of

Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export.

PubMed

White, Phillip J; Lapworth, Amanda L; An, Jie; Wang, Liping; McGarrah, Robert W; Stevens, Robert D; Ilkayeva, Olga; George, Tabitha; Muehlbauer, Michael J; Bain, James R; Trimmer, Jeff K; Brosnan, M Julia; Rolph, Timothy P; Newgard, Christopher B

2016-07-01

A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. Zucker-lean rats (ZLR) and Zucker-fatty rats (ZFR) were fed either a custom control, low fat (LF) diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val) were reduced by 45% (LF-RES). We performed comprehensive metabolic and physiologic profiling to characterize the effects of BCAA restriction on energy balance, insulin sensitivity, and glucose, lipid and amino acid metabolism. LF-fed ZFR had higher levels of circulating BCAA and lower levels of glycine compared to LF-fed ZLR. Feeding ZFR with the LF-RES diet lowered circulating BCAA to levels found in LF-fed ZLR. Activity of the rate limiting enzyme in the BCAA catabolic pathway, branched chain keto acid dehydrogenase (BCKDH), was lower in liver but higher in skeletal muscle of ZFR compared to ZLR and was not responsive to diet in either tissue. BCAA restriction had very little impact on metabolites studied in liver of ZFR where BCAA content was low, and BCKDH activity was suppressed. However, in skeletal muscle of LF-fed ZFR compared to LF-fed ZLR, where BCAA content and BCKDH activity were increased, accumulation of fatty acyl CoAs was completely normalized by dietary BCAA restriction. BCAA restriction also normalized skeletal muscle glycine content and increased urinary acetyl glycine excretion in ZFR. These effects were accompanied by lower RER and improved skeletal muscle insulin sensitivity in LF-RES fed ZFR as measured by hyperinsulinemic-isoglycemic clamp. Our data are consistent with a model wherein elevated circulating BCAA contribute to development of

Impaired Ca2+ handling in penile arteries from prediabetic Zucker rats: involvement of Rho kinase.

PubMed

Villalba, Nuria; Contreras, Cristina; Hernández, Medardo; García-Sacristán, Albino; Prieto, Dolores

2011-06-01

Diabetes is associated with an increased vascular tone usually involved in the pathogenesis of diabetic cardiovascular complications such as hypertension, stroke, coronary artery disease, or erectile dysfunction (ED). Enhanced contractility of penile erectile tissue has been associated with augmented activity of the RhoA/Rho kinase (RhoK) pathway in models of diabetes-associated ED. The present study assessed whether abnormal vasoconstriction in penile arteries from prediabetic obese Zucker rats (OZRs) is due to changes in the intracellular Ca(2+) concentration ([Ca(2+)](i)) and/or in myofilament Ca(2+) sensitivity. Penile arteries from OZRs and lean Zucker rats (LZRs) were mounted on microvascular myographs for simultaneous measurements of [Ca(2+)](i) and tension. The relationships between [Ca(2+)](i) and contraction for the α(1)-adrenergic vasoconstrictor phenylephrine (PE) were left shifted and steeper in OZRs compared with LZRs, although the magnitude of the contraction was similar in both groups. In contrast, the vasoconstriction induced by the thromboxane A(2) receptor agonist U-46619 was augmented in arteries from OZRs, and this increase was associated with an increase in both the sensitivity and maximum responses to Ca(2+). The RhoK inhibitor Y-27632 (10 μM) reduced the vasoconstriction induced by PE to a greater extent in OZRs than in LZRs, without altering Ca(2+). Y-27632 inhibited with a greater potency the contraction elicited by high KCl in arteries from OZRs compared with LZRs without changing [Ca(2+)](i). RhoK-II expression was augmented in arteries from OZRs. These results suggest receptor-specific changes in the Ca(2+) handling of penile arteries under conditions of metabolic syndrome. Whereas augmented vasoconstriction upon activation of the thromboxane A(2) receptor is coupled to enhanced Ca(2+) entry, a RhoK-mediated enhancement of myofilament Ca(2+) sensitivity is coupled with the α(1)-adrenergic vasoconstriction in penile arteries from OZRs.

Impaired Laparotomy Wound Healing in Obese Rats

PubMed Central

Xing, Liyu; Culbertson, Eric J.; Wen, Yuan; Robson, Martin C.

2015-01-01

Background Obesity increases the risk of laparotomy dehiscence and incisional hernia. The aim of this study was to measure the biological effect of obesity on laparotomy wound healing and the formation of incisional hernias. Methods Normal-weight Sprague–Dawley (SD) and obese Zucker rats were used in an established laparotomy wound healing and incisional ventral hernia model. Mechanical testing was performed on abdominal wall strips collected from laparotomy wounds. Hernia size was measured by digital imaging. Picrosirius staining for collagen isoforms was observed with polarized microscopy. Abdominal wall fibroblasts were cultured to measure collagen matrix remodeling and proliferation. Results Laparotomy wound healing was significantly impaired in obese rats. Mechanical strength was lower than in normal-weight rats. Yield load was reduced in the obese group at all time points. Picrosirius red staining showed increased immature type III collagen content and disorganized type I collagen fibers within laparotomy wounds of obese rats. Wound size was significantly larger in the obese group. Collagen matrix remodeling was impaired with fibroblasts from obese rats, but there was no difference in fibroblast proliferation between the obese and normal-weight groups. Conclusions We observed for the first time that laparotomy wound healing is impaired in obese rats. The recovery of laparotomy wound strength is delayed due to abnormal collagen maturation and remodeling, possibly due to a defect in fibroblast function. Strategies to improve outcomes for laparotomy wound healing in obese patients should include correcting the wound healing defect, possibly with growth factor or cell therapy. PMID:21347822

Mechanisms of lower maintenance dose of tacrolimus in obese patients.

PubMed

Sawamoto, Kazuki; Huong, Tran T; Sugimoto, Natsumi; Mizutani, Yuka; Sai, Yoshimichi; Miyamoto, Ken-ichi

2014-01-01

A retrospective analysis suggested that blood tacrolimus concentrations were consistent among patients with a body mass index (BMI) that was lean (<18.5), normal (≥ 18.5 and <25) or overweight/obese (≥ 25). The average maintenance dose of tacrolimus in patients with BMI ≥ 25 was significantly lower compared with that in patients with a BMI of less than 25. Lean and obese Zucker rats fed a normal diet were given tacrolimus intravenously or orally. The blood concentrations of tacrolimus in obese rats were significantly higher than those in lean rats after administration via both routes. The moment analysis has suggested that CLtot and Vdss of tacrolimus were not significantly different between lean and obese rats. The bioavailability was higher in obese rats, compared with that in lean rats. The protein expression of Cyp3a2 in the liver was significantly decreased in obese rats, compared with lean rats, while P-gp in the small intestine was also significantly decreased in obese rats. These results suggested that the steady-state trough concentration of tacrolimus in obese patients was well maintained by a relatively low dose compared with that in normal and lean patients, presumably due to increased bioavailability.

The effects of repetitive vibration on sensorineural function: biomarkers of sensorineural injury in an animal model of metabolic syndrome

PubMed Central

Kiedrowski, Megan; Waugh, Stacey; Miller, Roger; Johnson, Claud; Krajnak, Kristine

2016-01-01

Exposure to hand-transmitted vibration in the work-place can result in the loss of sensation and pain in workers. These effects may be exacerbated by pre-existing conditions such as diabetes or the presence of primary Raynaud's phenomena. The goal of these studies was to use an established model of vibration-induced injury in Zucker rats. Lean Zucker rats have a normal metabolic profile, while obese Zucker rats display symptoms of metabolic disorder or Type II diabetes. This study examined the effects of vibration in obese and lean rats. Zucker rats were exposed to 4 h of vibration for 10 consecutive days at a frequency of 125 Hz and acceleration of 49 m/s2 for 10 consecutive days. Sensory function was checked using transcutaneous electrical stimulation on days 1, 5 and 9 of the exposure. Once the study was complete the ventral tail nerves, dorsal root ganglia and spinal cord were dissected, and levels of various transcripts involved in sensorineural dysfunction were measured. Sensorineural dysfunction was assessed using transcutaneous electrical stimulation. Obese Zucker rats displayed very few changes in sensorineural function. However they did display significant changes in transcript levels for factors involved in synapse formation, peripheral nerve remodeling, and inflammation. The changes in transcript levels suggested that obese Zucker rats had some level of sensory nerve injury prior to exposure, and that exposure to vibration activated pathways involved in injury and re-innervation. PMID:26433044

Astrocytes increase barrier properties and ZO-1 expression in retinal vascular endothelial cells.

PubMed

Gardner, T W; Lieth, E; Khin, S A; Barber, A J; Bonsall, D J; Lesher, T; Rice, K; Brennan, W A

1997-10-01

Diabetic retinopathy and other diseases associated with retinal edema are characterized by increased microvascular leakage. Astrocytes have been proposed to maintain endothelial function in the brain, suggesting that glial impairment may underlie the development of retinal edema. The purpose of this study was to test the effects of astrocytes on barrier properties in retinal microvascular endothelial cells. Bovine retinal microvascular endothelial cells were exposed to conditioned media from rat brain astrocytes. Transendothelial electrical resistance (TER) was determined on 24-mm Transwell (Cambridge, MA) polycarbonate filters with the End-Ohm device (World Precision Instruments, Sarasota, FL). ZO-1 protein content was quantified by microtiter enzyme-linked immunosorbent assay. Astrocyte-conditioned medium (ACM) significantly increased TER (P < 0.0001) and ZO-1 content (P < 0.01). Both serum-containing and serum-free N1B defined ACM increased ZO-1 expression, but heating abolished the effect. Serum-free ACM decreased cell proliferation by 16%. Astrocytes release soluble, heat-labile factors that increase barrier properties and tight junction protein content. These results suggest that astrocytes enhance blood-retinal barrier properties, at least in part by increasing tight junction protein expression. Our findings suggest that glial malfunction plays an important role in the pathogenesis of vasogenic retinal edema.

PARP-1 may be involved in hydroquinone-induced apoptosis by poly ADP-ribosylation of ZO-2

PubMed Central

Liu, Jiaxian; Yuan, Qian; Ling, Xiaoxuan; Tan, Qiang; Liang, Hairong; Chen, Jialong; Lin, Lianzai; Xiao, Yongmei; Chen, Wen; Liu, Linhua; Tang, Huanwen

2017-01-01

Hydroquinone (HQ), a major reactive metabolite of benzene, contributes to benzene-induced leukemia. The molecular mechanisms that underlie this activity remain to be elucidated. Poly ADP-ribosylation (PARylation) is a type of reversible posttranslational modification that is performed by enzymes in the PAR polymerase (PARP) family and mediates different biological processes, including apoptosis. Zona occludens 2 (ZO-2) is a tight junction scaffold protein, which is involved in cell proliferation and apoptosis. The present study investigated the activity and mechanisms regulated by PARP-1 during HQ-induced apoptosis using TK6 lymphoblastoid cells and PARP-1-silenced TK6 cells. The results revealed that exposure to 10 µM HQ for 72 h induced apoptosis in TK6 cells and that apoptosis was attenuated in PARP-1-silenced TK6 cells. In cells treated with HQ, inhibition of PARP-1 increased the expression of B cell leukemia/lymphoma 2 (Bcl-2), increased ATP production and reduced reactive oxygen species (ROS) production relative to the levels observed in cells treated with HQ alone. Co-localization of ZO-2 and PAR (or PARP-1 protein) was determined using immunofluorescence confocal microscopy. The findings of the present study revealed that ZO-2 was PARylated via an interaction with PARP-1, which was consistent with an analysis of protein expression that was performed using western blot analysis, which determined that ZO-2 protein expression was upregulated in HQ-treated control cells and downregulated in HQ-treated PARP-1-silenced TK6 cells. These findings indicated that prolonged exposure to a low dose of HQ induced TK6 cells to undergo apoptosis, whereas inhibiting PARP-1 attenuates cellular apoptosis by activating Bcl-2 and energy-saving processes and reducing ROS. The present study determined that PARP-1 was involved in HQ-induced apoptosis by PARylation of ZO-2. PMID:28983606

Oral Administration of Interferon Tau Enhances Oxidation of Energy Substrates and Reduces Adiposity in Zucker Diabetic Fatty Rats

PubMed Central

Tekwe, Carmen D.; Lei, Jian; Yao, Kang; Rezaei, Reza; Li, Xilong; Dahanayaka, Sudath; Carroll, Raymond J.; Meininger, Cynthia J.; Bazer, Fuller W.; Wu, Guoyao

2013-01-01

Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4 or 8 μg IFNT/kg body weight (BW) per day (n=6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary glucose and ketone bodies were tested daily. Rates of glucose and oleate oxidation in liver, brown adipose tissue, and abdominal adipose tissue, leucine catabolism in skeletal muscle, and lipolysis in white and brown adipose tissues were greater for rats treated with 8 μg IFNT/kg BW/day in comparison with control rats. Treatment with 8 μg IFNT/kg BW/day increased heat production, reduced BW gain and adiposity, ameliorated fatty liver syndrome, delayed the onset of diabetes, and decreased concentrations of glucose, free fatty acids, triacylglycerol, cholesterol, and branched-chain amino acids in plasma, compared to control rats. Oral administration of 8 μg IFNT/kg BW/day ameliorated oxidative stress in skeletal muscle, liver and adipose tissue, as indicated by decreased ratios of oxidized glutathione to reduced glutathione and increased concentrations of the antioxidant tetrahydrobiopterin. These results indicate that IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats and may have broad important implications for preventing and treating obesity-related diseases in mammals. PMID:23804503

Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis in Zucker diabetic fatty rats: Activation of PPAR-{alpha}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsun-Wei Huang, Tom; Peng Gang; Qian Li, George

Salacia oblonga (SO) root is an Ayurvedic medicine with anti-diabetic and anti-obese properties. Peroxisome proliferator-activated receptor (PPAR)-{alpha}, a nuclear receptor, plays an important role in maintaining the homeostasis of lipid metabolism. Here, we demonstrate that chronic oral administration of the water extract from the root of SO to Zucker diabetic fatty (ZDF) rats, a genetic model of type 2 diabetes and obesity, lowered plasma triglyceride and total cholesterol (TC) levels, increased plasma high-density lipoprotein levels and reduced the liver contents of triglyceride, non-esterified fatty acids (NEFA) and the ratio of fatty droplets to total tissue. By contrast, the extract hadmore » no effect on plasma triglyceride and TC levels in fasted ZDF rats. After olive oil administration to ZDF the extract also inhibited the increase in plasma triglyceride levels. These results suggest that SO extract improves postprandial hyperlipidemia and hepatic steatosis in ZDF rats. Additionally, SO treatment enhanced hepatic expression of PPAR-{alpha} mRNA and protein, and carnitine palmitoyltransferase-1 and acyl-CoA oxidase mRNAs in ZDF rats. In vitro, SO extract and its main component mangiferin activated PPAR-{alpha} luciferase activity in human embryonic kidney 293 cells and lipoprotein lipase mRNA expression and enzyme activity in THP-1 differentiated macrophages; these effects were completely suppressed by a selective PPAR-{alpha} antagonist MK-886. The findings from both in vivo and in vitro suggest that SO extract functions as a PPAR-{alpha} activator, providing a potential mechanism for improvement of postprandial hyperlipidemia and hepatic steatosis in diabetes and obesity.« less

Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats.

PubMed

Qiu, Lian-Bo; Zhou, Yan; Wang, Qi; Yang, Long-Long; Liu, Hai-Qiang; Xu, Sheng-Long; Qi, Yu-Hong; Ding, Gui-Rong; Guo, Guo-Zhen

2011-07-11

Previously we found that exposure to electromagnetic pulse (EMP) induced an increase in blood-brain-barrier (BBB) permeability and the degradation of tight junction protein ZO-1 in rats. Matrix metalloproteinases (MMPs), in particular gelatinases (MMP-2 and MMP-9), play a key role in degradation of tight junction proteins, are known mediators of BBB compromise. We hypothesized that the degradation of ZO-1 by gelatinases contributed to EMP-induced BBB opening. To test this hypothesis, the mRNA level of ZO-1, protein levels of MMP-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) were detected in rat cerebral cortex after exposing rats to EMP at 200 kV/m for 200 pulses. It was found that the mRNA level of ZO-1 was unaltered at different time points after EMP exposure. The protein levels of MMP-2 and MMP-9 significantly increased at 3 h and 0.5 h, respectively. However, TIMP-1 (inhibitor of MMP-9) and TIMP-2 (inhibitor of MMP-2) only moderately increased after EMP exposure. In addition, in situ zymography results showed that the gelatinase activity increased in cerebral microvessels at 3 h after EMP exposure. When rats were treated with gelatinases inhibitor (SB-3CT) before EMP exposure, the EMP-induced BBB opening was attenuated and the ZO-1 degradation was reversed. Our results suggested that EMP-induced BBB opening was related to gelatinase mediated ZO-1 degradation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Combined Intervention with Germinated Vigna radiata and Aerobic Interval Training Protocol Is an Effective Strategy for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) and Other Alterations Related to the Metabolic Syndrome in Zucker Rats.

PubMed

Kapravelou, Garyfallia; Martínez, Rosario; Nebot, Elena; López-Jurado, María; Aranda, Pilar; Arrebola, Francisco; Cantarero, Samuel; Galisteo, Milagros; Porres, Jesus M

2017-07-19

Metabolic syndrome (MetS) is a group of related metabolic alterations that increase the risk of developing non-alcoholic fatty liver disease (NAFLD). Several lifestyle interventions based on dietary treatment with functional ingredients and physical activity are being studied as alternative or reinforcement treatments to the pharmacological ones actually in use. In the present experiment, the combined treatment with mung bean ( Vigna radiata ), a widely used legume with promising nutritional and health benefits that was included in the experimental diet as raw or 4 day-germinated seed flour, and aerobic interval training protocol (65-85% VO₂ max) has been tested in lean and obese Zucker rats following a 2 × 2 × 2 (2 phenotypes, 2 dietary interventions, 2 lifestyles) factorial ANOVA (Analysis of Variance) statistical analysis. Germination of V. radiata over a period of four days originated a significant protein hydrolysis leading to the appearance of low molecular weight peptides. The combination of 4 day-germinated V. radiata and aerobic interval training was more efficient compared to raw V. radiata at improving the aerobic capacity and physical performance, hepatic histology and functionality, and plasma lipid parameters as well as reverting the insulin resistance characteristic of the obese Zucker rat model. In conclusion, the joint intervention with legume sprouts and aerobic interval training protocol is an efficient treatment to improve the alterations of glucose and lipid metabolism as well as hepatic histology and functionality related to the development of NAFLD and the MetS.

Recombinant Human Sonic Hedgehog Protein Regulates the Expression of ZO-1 and Occludin by Activating Angiopoietin-1 in Stroke Damage

PubMed Central

Chen, Sheng-cai; Huang, Ming; Wang, Yong; Gao, Yuan; Huang, Yan; Wang, Meng-die; Mao, Ling; Hu, Bo

2013-01-01

This study examines the regulating effect of Sonic Hedgehog (Shh) on the permeability of the blood-brain barrier (BBB) in cerebral ischemia. By employing permanent middle cerebral artery occlusion (pMCAO) model, we find that Shh significantly decreases brain edema and preserves BBB permeability. Moreover, Shh increases zonula occludens-1 (ZO-1), occludin and angiopiotetin-1 (Ang-1) expression in the ischemic penumbra. Blockage of Shh with cyclopamine abolishes the effects of Shh on brain edema, BBB permeability and ZO-1, occludin, Ang-1 expression. Primary brain microvessel endothelial cells (BMECs) and astrocytes were pre-treated with Shh, cyclopamine, Ang-1-neutralizing antibody, and subjected to oxygen-glucose deprivation (OGD). Results show that the Ang-1 protein level in the culture medium of Shh-treated astrocytes is significantly higher. Shh also increased ZO-1, occludin and Ang-1 expression in BMECs, while cyclopamine and Ang-1-neutralizing antibody inhibited the effects of Shh on the ZO-1 and occludin expression, respectively. This study suggests that, under ischemic insults, Shh triggers Ang-1 production predominantly in astrocytes, and the secreted Ang-1 acts on BMECs, thereby upregulating ZO-1 and occludin to repair the tight junction and ameliorate the brain edema and BBB leakage. PMID:23894369

Effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise on markers of bone metabolism, microarchitecture and turnover in obese Zucker rats.

PubMed

Nebot, Elena; Aparicio, Virginia A; Coll-Risco, Irene; Camiletti-Moirón, Daniel; Schneider, Johannes; Kapravelou, Garyfallia; Heimel, Patrick; Martínez, Rosario; Andrade, Ana; Slezak, Paul; Redl, Heinz; Porres, Jesús M; López-Jurado, María; Pietschmann, Peter; Aranda, Pilar

2016-11-01

Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome, and the protein level of the diets seem to be crucial for the development and maintenance of bone. The nature of exercise and whether exercise in combination with moderately high-protein dietary interventions could protect against potential bone mass deficits remains unclear. To investigate the effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise (IASE) protocol on bone status, and to assess potential interaction effects (i.e. diet*IASE). Male Zucker fatty rats were randomized distributed into 4 groups (n=8): normoprotein+sedentary; normoprotein+exercise; moderately high-protein+sedentary, and moderately high-protein+exercise. Training groups conducted an IASE program, 5days/week for 2months. Markers of bone metabolism were measured in plasma. Parameters of bone mass and 3D outcomes for trabecular and cortical bone microarchitecture were assessed by micro-computed tomography. Femur length, plasma osteocalcin, sclerostin, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, insulin, leptin, PTH, uric acid and urinary phosphorus levels were lower in the moderately high-protein compared to the normoprotein groups (all, p<0.05), whereas plasma alkaline phosphatase, aspartate aminotransferase, alanine transaminase, and urinary uric acid concentrations, and cortical total volume (TV) and bone volume (BV) were higher in the moderately high-protein (all, p<0.01). Final body weight and alkaline phosphatase levels were lower in the exercise compared to the sedentary (both, p<0.05), whereas femur length and weight, aminoterminal propeptides of type I procollagen and C-terminal telopeptides of type I collagen concentrations, and cortical TV and BV were higher in the exercise compared to the sedentary groups (all, p<0.05). The combination of interventions may be effective to enhance trabecular bone

Remote ischemic preconditioning fails to reduce infarct size in the Zucker fatty rat model of type-2 diabetes: role of defective humoral communication.

PubMed

Wider, Joseph; Undyala, Vishnu V R; Whittaker, Peter; Woods, James; Chen, Xuequn; Przyklenk, Karin

2018-03-09

Remote ischemic preconditioning (RIPC), the phenomenon whereby brief ischemic episodes in distant tissues or organs render the heart resistant to infarction, has been exhaustively demonstrated in preclinical models. Moreover, emerging evidence suggests that exosomes play a requisite role in conveying the cardioprotective signal from remote tissue to the myocardium. However, in cohorts displaying clinically common comorbidities-in particular, type-2 diabetes-the infarct-sparing effect of RIPC may be confounded for as-yet unknown reasons. To investigate this issue, we used an integrated in vivo and in vitro approach to establish whether: (1) the efficacy of RIPC is maintained in the Zucker fatty rat model of type-2 diabetes, (2) the humoral transfer of cardioprotective triggers initiated by RIPC are transported via exosomes, and (3) diabetes is associated with alterations in exosome-mediated communication. We report that a standard RIPC stimulus (four 5-min episodes of hindlimb ischemia) reduced infarct size in normoglycemic Zucker lean rats, but failed to confer protection in diabetic Zucker fatty animals. Moreover, we provide novel evidence, via transfer of serum and serum fractions obtained following RIPC and applied to HL-1 cardiomyocytes subjected to hypoxia-reoxygenation, that diabetes was accompanied by impaired humoral communication of cardioprotective signals. Specifically, our data revealed that serum and exosome-rich serum fractions collected from normoglycemic rats attenuated hypoxia-reoxygenation-induced HL-1 cell death, while, in contrast, exosome-rich samples from Zucker fatty rats did not evoke protection in the HL-1 cell model. Finally, and unexpectedly, we found that exosome-depleted serum from Zucker fatty rats was cytotoxic and exacerbated hypoxia-reoxygenation-induced cardiomyocyte death.

Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium.

PubMed

Czompa, Attila; Gyongyosi, Alexandra; Szoke, Kitti; Bak, Istvan; Csepanyi, Evelin; Haines, David D; Tosaki, Arpad; Lekli, Istvan

2017-03-20

Objective : A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods : Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin-water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM). Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup. Results : Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in blood of ZO

NHS-A isoform of the NHS gene is a novel interactor of ZO-1.

PubMed

Sharma, Shiwani; Koh, Katrina S Y; Collin, Caitlin; Dave, Alpana; McMellon, Amy; Sugiyama, Yuki; McAvoy, John W; Voss, Anne K; Gécz, Jozef; Craig, Jamie E

2009-08-15

Mutations in the NHS (Nance-Horan Syndrome) gene lead to severe congenital cataracts, dental defects and sometimes mental retardation. NHS encodes two protein isoforms, NHS-A and -1A that display cell-type dependent differential expression and localization. Here we demonstrate that of these two isoforms, the NHS-A isoform associates with the cell membrane in the presence of intercellular contacts and it immunoprecipitates with the tight junction protein ZO-1 in MDCK (Madin Darby Canine Kidney) epithelial cells and in neonatal rat lens. The NHS-1A isoform however is a cytoplasmic protein. Both Nhs isoforms are expressed during mouse development. Immunolabelling of developing mouse with the anti-NHS antibody that detects both isoforms revealed the protein in the developing head including the eye and brain. It was primarily expressed in epithelium including neural epithelium and certain vascular endothelium but only weakly expressed in mesenchymal cells. In the epithelium and vascular endothelium the protein associated with the cell membrane and co-localized with ZO-1, which indirectly indicates expression of the Nhs-A isoform in these structures. Membrane localization of the protein in the lens vesicle similarly supports Nhs-A expression. In conclusion, the NHS-A isoform of NHS is a novel interactor of ZO-1 and may have a role at tight junctions. This isoform is important in mammalian development especially of the organs in the head.

The N and C Termini of ZO-1 Are Surrounded by Distinct Proteins and Functional Protein Networks*

PubMed Central

Van Itallie, Christina M.; Aponte, Angel; Tietgens, Amber Jean; Gucek, Marjan; Fredriksson, Karin; Anderson, James Melvin

2013-01-01

The proteins and functional protein networks of the tight junction remain incompletely defined. Among the currently known proteins are barrier-forming proteins like occludin and the claudin family; scaffolding proteins like ZO-1; and some cytoskeletal, signaling, and cell polarity proteins. To define a more complete list of proteins and infer their functional implications, we identified the proteins that are within molecular dimensions of ZO-1 by fusing biotin ligase to either its N or C terminus, expressing these fusion proteins in Madin-Darby canine kidney epithelial cells, and purifying and identifying the resulting biotinylated proteins by mass spectrometry. Of a predicted proteome of ∼9000, we identified more than 400 proteins tagged by biotin ligase fused to ZO-1, with both identical and distinct proteins near the N- and C-terminal ends. Those proximal to the N terminus were enriched in transmembrane tight junction proteins, and those proximal to the C terminus were enriched in cytoskeletal proteins. We also identified many unexpected but easily rationalized proteins and verified partial colocalization of three of these proteins with ZO-1 as examples. In addition, functional networks of interacting proteins were tagged, such as the basolateral but not apical polarity network. These results provide a rich inventory of proteins and potential novel insights into functions and protein networks that should catalyze further understanding of tight junction biology. Unexpectedly, the technique demonstrates high spatial resolution, which could be generally applied to defining other subcellular protein compartmentalization. PMID:23553632

Childhood-Adolescent Obesity in the Cardiorenal Syndrome: Lessons from Animal Models

PubMed Central

Hayden, Melvin R.; Sowers, James R.

2011-01-01

Background/Aims Childhood-adolescent overweight and obesity have grown to pandemic proportions during the past decade. The onset of obesity in younger adults will likely be manifested as earlier onset of myocardial and renal end-organ disease in younger adults. For the first time, it is estimated that the current generation may not live to be as old as their parents. Thus, it is important to develop animal models of childhood obesity to understand fundamental pathological organ changes. Methods In this regard, we utilize transmission electron microscopy evaluation to evaluate early remodeling changes of two adolescent rodent obesity models: the Zucker obese (fa/fa) rat and the db/db mouse models of obesity. We have concentrated on the initial ultrastructural remodeling (obese adipose tissue, skeletal muscle, and islet remodeling) and the associated changes in target end organs (including the myocardium and kidney) in young rodent models of obesity and insulin resistance, collectively manifesting as the cardiorenal metabolic syndrome (CRS). Results Briefly, tissues revealed the following ultrastructural remodeling abnormalities: inflammation, hypertrophy, and early fibrosis in adipose tissue; loss of mitochondria in skeletal muscles, hyperplasia, fibrosis, and depletion of insulin-secretory granules in pancreatic islets; increased intramyocardial lipid accumulation, fibrosis, and mitochondrial deposition in the myocardium, and obesity-related glomerulopathy and tubulopathy in the kidney. Conclusion Based on the current knowledge and ultrastructural observations of organ pathology, we propose mechanisms whereby obesity appears to be the driving force behind the development of the CRS. PMID:22294984

Baicalin Protects against TNF-α-Induced Injury by Down-Regulating miR-191a That Targets the Tight Junction Protein ZO-1 in IEC-6 Cells.

PubMed

Wang, Li; Zhang, Ren; Chen, Jian; Wu, Qihui; Kuang, Zaoyuan

2017-04-01

Tumor necrosis factor-alpha (TNF-α) plays an important role in the developing process of inflammatory bowel disease. Tight junction protein zonula occludens-1 (ZO-1), one of epithelial junctional proteins, maintains the permeability of intestinal barrier. The objective of this study was to investigate the mechanism of the protective effect of baicalin on TNF-α-induced injury and ZO-1 expression in intestinal epithelial cells (IECs). We found that baicalin pretreatment significantly improved cell viability and cell migration following TNF-α stimulation. miR-191a inhibitor increased the protective effect of baicalin on cell motility injured by TNF-α. In addition, miR-191a down-regulated the mRNA and protein level of its target gene ZO-1. TNF-α stimulation increased miR-191a expression, leading to the decline of ZO-1 mRNA and protein. Moreover, pretreatment with baicalin reversed TNF-α induced decrease of ZO-1 and increase of miR-191a, miR-191a inhibitor significantly enhanced ZO-1 protein expression restored by baicalin. These results indicate that baicalin exerts a protective effect on IEC-6 (rat small intestinal epithelial cells) cells against TNF-α-induced injury, which is at least partly via inhibiting the expression of miR-191a, thus increasing ZO-1 mRNA and protein levels.

Up-regulation of the tight-junction protein ZO-1 by substance P and IGF-1 in A431 cells.

PubMed

Ko, Ji-Ae; Murata, Shizuka; Nishida, Teruo

2009-08-01

The formation of a barrier by tight junctions is important in epithelia of various tissues. Substance P (SP) and insulin-like growth factor (IGF)-1 synergistically promote barrier function in the corneal epithelium. We have now examined the effects of SP and IGF-1 on expression of the tight-junction protein zonula occludens (ZO)-1 in A431 human epidermoid carcinoma cells. Reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analyses revealed that SP and IGF-1 increased the amounts of ZO-1 mRNA and protein in these cells in a concentration-dependent manner, with neither SP nor IGF-1 alone having such an effect. The SP- and IGF-1-induced up-regulation of ZO-1 was accompanied by phosphorylation of extracellular signal-regulated kinase (ERK), and both of these effects were blocked by PD98059, an inhibitor of ERK activation. SP and IGF-1 also increased the transepithelial electrical resistance (TER) (an indicator of barrier function) of an A431 cell monolayer in a manner sensitive to PD98059. Our results thus suggest that the synergistic induction of ZO-1 expression by SP and IGF-1 may promote barrier function in skin epithelial cells. (c) 2009 John Wiley & Sons, Ltd.

[Effects of N-butylphthalide on the expressions of ZO-1 and claudin-5 in blood-brain barrier of rats with acute carbon monoxide poisoning].

PubMed

Wang, Li; Ding, Xiaoyu; Bi, Mingjun; Wang, Jinglin; Zou, Yong; Tang, Jiyou; Li, Qin

2018-05-01

To explore the effects of N-butylphthalide on the expressions of ZO-1 and claudin-5 in blood-brain barrier (BBB) in rats with acute carbon monoxide (CO) poisoning. A total of 144 adult healthy male Sprague-Dawley (SD) rats were randomly divided into normal control group, CO poisoning group, and NBP treatment group, with 48 rats in each group. The acute CO poisoning model was reproduced in hyperbaric oxygen chamber, and all model rats were given hyperbaric oxygen therapy once daily. The rats in the normal control group were free to breathe fresh air. The rats in NBP treatment group were administered orally NBP 60 mg/kg twice a day at 2 hours after poisoning until death. The rats in normal control group and CO poisoning group were treated with equal amount of pure olive oil. Four rats were sacrificed from each group at 1, 3, 7, 14 days after model reproducing, respectively. The changes in ultrastructure of BBB were observed under transmission electron microscope. The expressions of ZO-1 and claudin-5 proteins were determined by immunofluorescence staining and Western Blot. The localization of the two target proteins was observed by immunofluorescence double staining. The correlation between the two proteins was analyzed by linear regression. The ultrastructure of BBB was normal in normal control group, some ZO-1 and a large number of claudin-5 positive cells were observed. The ultrastructure of BBB was seriously injured, ZO-1 and claudin-5 positive cells in brain tissue were significantly decreased, and the expressions of ZO-1 and claudin-5 proteins in brain tissue at 1 day after poisoning in CO poisoning group were significantly lower than those of normal control group (ZO-1 protein: 3.38±0.30 vs. 24.50±5.62, claudin-5 protein: 11.38±0.93 vs. 46.35±6.88, both P < 0.05), and although gradually restored, they were maintained at relatively lower levels until 14 days as compared with those in normal control group (ZO-1 protein: 10.35±0.80 vs. 24.63±3.57, claudin-5

Resistance training inhibits the elevation of skeletal muscle derived-BDNF level concomitant with improvement of muscle strength in zucker diabetic rat

PubMed Central

Kim, Hee-Jae; So, Byunghun; Son, Jun Seok; Song, Han Sol; Oh, Seung Lyul; Seong, Je Kyung; Lee, Hoyoung; Song, Wook

2015-01-01

[Purpose] In the present study, we investigated the effects of 8 weeks of progressive resistance training on the level of skeletal muscle derived BDNF as well as glucose intolerance in Zucker diabetic rats. [Methods] Six week-old male Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were randomly divided into 3 groups: sedentary ZLC (ZLC-Con), sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). Progressive resistance training using a ladder and tail weights was performed for 8 weeks (3 days/week). [Results] After 8 weeks of resistance training, substantial reduction in body weight was observed in ZDF-Ex compared to ZDF-Con. Though the skeletal muscle volume did not change, grip strength grip strength was significantly higher in ZDF-Ex compared to ZDF-Con. In the soleus, the level of BDNF was increased in ZDF-Con, but was significantly decreased (p<0.05) in ZDF-Ex, showing a training effect. Moreover, we found that there was a negative correlation (r=-0.657; p=0.004) between grip strength and BDNF level whereas there was a positive correlation (r=0.612; p=0.008) between plasma glucose level and BDNF level in skeletal muscle. [Conclusion] Based upon our results, we demonstrated that resistance training inhibited the elevation of skeletal muscle derived-BDNF expression concomitant with the improvement of muscle strength in zucker diabetic rats. In addition, muscle-derived BDNF might be a potential mediator for the preventive effect of resistance training on the progress of type 2 diabetes. PMID:27274460

Alterations in Glutathione Redox Metabolism, Oxidative Stress, and Mitochondrial Function in the Left Ventricle of Elderly Zucker Diabetic Fatty Rat Heart

PubMed Central

Raza, Haider; John, Annie; Howarth, Frank C.

2012-01-01

The Zucker diabetic fatty (ZDF) rat is a genetic model in which the homozygous (FA/FA) male animals develop obesity and type 2 diabetes. Morbidity and mortality from cardiovascular complications, due to increased oxidative stress and inflammatory signals, are the hallmarks of type 2 diabetes. The precise molecular mechanism of contractile dysfunction and disease progression remains to be clarified. Therefore, we have investigated molecular and metabolic targets in male ZDF (30–34 weeks old) rat heart compared to age matched Zucker lean (ZL) controls. Hyperglycemia was confirmed by a 4-fold elevation in non-fasting blood glucose (478.43 ± 29.22 mg/dL in ZDF vs. 108.22 ± 2.52 mg/dL in ZL rats). An increase in reactive oxygen species production, lipid peroxidation and oxidative protein carbonylation was observed in ZDF rats. A significant increase in CYP4502E1 activity accompanied by increased protein expression was also observed in diabetic rat heart. Increased expression of other oxidative stress marker proteins, HO-1 and iNOS was also observed. GSH concentration and activities of GSH-dependent enzymes, glutathione S-transferase and GSH reductase, were, however, significantly increased in ZDF heart tissue suggesting a compensatory defense mechanism. The activities of mitochondrial respiratory enzymes, Complex I and Complex IV were significantly reduced in the heart ventricle of ZDF rats in comparison to ZL rats. Western blot analysis has also suggested a decreased expression of IκB-α and phosphorylated-JNK in diabetic heart tissue. Our results have suggested that mitochondrial dysfunction and increased oxidative stress in ZDF rats might be associated, at least in part, with altered NF-κB/JNK dependent redox cell signaling. These results might have implications in the elucidation of the mechanism of disease progression and designing strategies for diabetes prevention. PMID:23203193

Endothelin antagonism improves hepatic insulin sensitivity associated with insulin signaling in Zucker fatty rats.

PubMed

Berthiaume, Nathalie; Carlson, Christian J; Rondinone, Cristina M; Zinker, Bradley A

2005-11-01

In the present study, we investigated the effects of long-term treatment with the endothelin (ET) antagonist atrasentan, an ET(A)-selective antagonist, on whole body glucose metabolism and insulin signaling in a commonly used model of insulin resistance, the Zucker fatty rat. Zucker lean and fatty rats were maintained for 6 weeks on either control or atrasentan-treated water. Euglycemic-hyperinsulinemic clamps (4 mU/kg per minute) were performed at the end of the 6-week treatment on a subset of rats (n=10/treatment). In another subset (n=5/treatment), an insulin tolerance test was performed; liver and muscle tissues were harvested 10 minutes following the challenge for further analysis. Results of the clamps demonstrated that long-term atrasentan treatment significantly increased whole body glucose metabolism in fatty rats compared with vehicle control subjects. Insulin-induced insulin receptor substrate 1 tyrosine and protein kinase B serine phosphorylation were significantly reduced in the liver and muscle of fatty animals compared with their lean littermates. This reduction was overcome with atrasentan treatment in the liver but not in the muscle. There was no difference between lean and fatty animals, however, in insulin receptor substrate 1 and protein kinase B protein expression in the liver and muscle and no effect by atrasentan. In contrast, expression of the regulatory subunit of PI-3 kinase (p85alpha) was significantly increased in the liver but not in the muscle of fatty animals compared with their lean littermates and this was normalized to levels of lean animals with atrasentan treatment. These findings indicate that long-standing ET antagonism improves whole body glucose metabolism in Zucker fatty rats through improvements in insulin signaling in the liver. These results indicate that therapeutic ET antagonism may assist in correcting the insulin-resistant state.

Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity.

PubMed

Heinrich, Garrett; Muturi, Harrison T; Rezaei, Khadijeh; Al-Share, Qusai Y; DeAngelis, Anthony M; Bowman, Thomas A; Ghadieh, Hilda E; Ghanem, Simona S; Zhang, Deqiang; Garofalo, Robert S; Yin, Lei; Najjar, Sonia M

2017-01-01

Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker ( fa/fa , ZDF) and Koletsky ( f/f ) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species.

Angelica archengelica extract induced perturbation of rat skin and tight junctional protein (ZO-1) of HaCaT cells

PubMed Central

Kaushal, N.; Naz, S.; Tiwary, AK.

2011-01-01

Background and purpose of the study Herbal enhancers compared to the synthetic ones have shown less toxis effects. Coumarins have been shown at concentrations inhibiting phospoliphase C-Y (Phc-Y) are able to enhance tight junction (TJ) permeability due to hyperpoalation of Zonolous Occludense-1 (ZO-1) proteins. The purpose of this study was to evaluate the influence of ethanolic extract of Angelica archengelica (AA-E) which contain coumarin on permeation of repaglinide across rat epidermis and on the tight junction plaque protein ZO-1 in HaCaT cells. Methods Transepidermal water loss (TEWL) from the rat skin treated with different concentrations of AA-E was assessed by Tewameter. Scanning and Transmission Electron Microscopy (TEM) on were performed on AA-E treated rat skin portions. The possibility of AA-E influence on the architecture of tight junctions by adverse effect on the cytoplasmic ZO-1 in HaCaT cells was investigated. Finally, the systemic delivery of repaglinide from the optimized transdermal formulation was investigated in rats. Results The permeation of repaglinide across excised rat epidermis was 7-fold higher in the presence of AA-E (5% w/v) as compared to propylene glycol:ethanol (7:3) mixture. The extract was found to perturb the lipid microconstituents in both excised and viable rat skin, although, the effect was less intense in the later. The enhanced permeation of repaglinide across rat epidermis excised after treatment with AA-E (5% w/v) for different periods was in concordance with the high TEWL values of similarly treated viable rat skin. Further, the observed increase in intercellular space, disordering of lipid structure and corneocyte detachment indicated considerable effect on the ultrastructure of rat epidermis. Treatment of HaCaT cell line with AA-E (0.16% w/v) for 6 hrs influenced ZO-1 as evidenced by reduced immunofluorescence of anti-TJP1 (ZO-1) antibody in Confocal Laser Scanning Microscopy studies (CLSM) studies. The plasma

Insulin-sensitizing effect of rosiglitazone (BRL-49653) by regulation of glucose transporters in muscle and fat of Zucker rats.

PubMed

Kramer, D; Shapiro, R; Adler, A; Bush, E; Rondinone, C M

2001-11-01

Thiazolidinediones (TZDs), a class of antidiabetic agents, are specific agonists of peroxisome proliferator activator receptor (PPARgamma). However, their mechanisms of action, and the in vivo target tissues that mediate insulin sensitization are not well understood. The aim of this study was to investigate the role of glucose transporters (GLUT-1 and GLUT-4) in the TZD insulin-sensitizer action. The effects of rosiglitazone treatment were studied using Zucker (fa/fa) rats after 7 days of oral dosing (3.6 mg/kg/d). Rosiglitazone lowered (approximate 80%) basal plasma insulin levels in obese rats and substantially corrected (approximately 50%) insulin resistance based upon results from hyperinsulinemic euglycemic clamp studies. GLUT-4 protein levels were reduced (approximately 75%) in adipose tissue of obese rats and treatment with rosiglitazone normalized them. Interestingly, GLUT-1 protein content was increased in adipose tissue ( thick approximate 150%) and skeletal muscle (approximately 50%) of obese rats and treatment with rosiglitazone increased it even more by 5.5-fold in fat and by 2.5-fold in muscle. Consistent with these results, basal (GLUT-1-mediated) transport rate of 3-O-methyl-D-glucose into isolated epitrochlearis muscle was elevated in response to rosiglitazone. Incubation of fully differentiated 3T3-L1 adipocytes with the drug for 7 days increased the levels of GLUT-1 protein, but did not affect GLUT-4 levels. In conclusion, rosiglitazone may improve insulin resistance in vivo by normalizing GLUT-4 protein content in adipose tissue and increasing GLUT-1 in skeletal muscle and fat. While the drug has a direct effect on GLUT-1 protein expression in vitro without a direct effect on GLUT-4 suggests that direct and indirect effects of rosiglitazone on glucose transporters may have an important role in improving insulin resistance in vivo. Copyright 2001 by W.B. Saunders Company

High temperature-ultra performance liquid chromatography-mass spectrometry for the metabonomic analysis of Zucker rat urine.

PubMed

Gika, Helen G; Theodoridis, Georgios; Extance, Jon; Edge, Anthony M; Wilson, Ian D

2008-08-15

The applicability and potential of using elevated temperatures and sub 2-microm porous particles in chromatography for metabonomics/metabolomics was investigated using, for the first time, solvent temperatures higher than the boiling point of water (up to 180 degrees C) and thermal gradients to reduce the use of organic solvents. Ultra performance liquid chromatography, combined with mass spectrometry, was investigated for the global metabolite profiling of the plasma and urine of normal and Zucker (fa/fa) obese rats (a well established disease animal model). "Isobaric" high temperature chromatography, where the temperature and flow rate follow a gradient program, was developed and evaluated against a conventional organic solvent gradient. LC-MS data were first examined by established chromatographic criteria in order to evaluate the chromatographic performance and next were treated by special peak picking algorithms to allow the application of multivariate statistics. These studies showed that, for urine (but not plasma), chromatography at elevated temperatures provided better results than conventional reversed-phase LC with higher peak capacity and better peak asymmetry. From a systems biology point of view, better group clustering and separation was obtained with a larger number of variables of high importance when using high temperature-ultra performance liquid chromatography (HT-UPLC) compared to conventional solvent gradients.

Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats

PubMed Central

Rideout, Todd C.; Carrier, Bradley; Wen, Shin; Raslawsky, Amy; Browne, Richard W.; Harding, Scott V.

2015-01-01

To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (−55%) than either the PS (−24%) or the αLA (−25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (−47%) or in combination with PS (−54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21–22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone. PMID:25664679

Trouble and Triumph: German Life-Turkish Tradition in Renan Demirkan's "Schwarzer Tee mit drei Stuck Zucker"

ERIC Educational Resources Information Center

Ebert, Reika

2004-01-01

This paper explores Demirkan's narrative strategies in "Schwarzer Tee mit drei Stuck Zucker" to negotiate issues of a life between two cultures and traditions. Based on Bhabha's insights that mainstream culture needs intellectual and artistic infusion from the margins of a society in order to remain vital; and that cultural production…

Inhibition of Gastric Lipase as a Mechanism for Body Weight and Plasma Lipids Reduction in Zucker Rats Fed a Rosemary Extract Rich in Carnosic Acid

PubMed Central

Romo Vaquero, María; Yáñez-Gascón, María-Josefa; García Villalba, Rocío; Larrosa, Mar; Fromentin, Emilie; Ibarra, Alvin; Roller, Marc; Tomás-Barberán, Francisco; Espín de Gea, Juan Carlos; García-Conesa, María-Teresa

2012-01-01

Background Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. Methods and Principal Findings RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. Conclusions Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption. PMID:22745826

Metabolic profiling of muscle contraction in lean compared with obese rodents.

PubMed

Thyfault, John P; Cree, Melanie G; Tapscott, Edward B; Bell, Jill A; Koves, Timothy R; Ilkayeva, Olga; Wolfe, Robert R; Dohm, G Lynis; Muoio, Deborah M

2010-09-01

Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose tolerance. Here, we used a hindlimb perfusion model to examine the impact of obesity and elevated IMTG levels on contraction-induced changes in skeletal muscle fuel metabolism. Comprehensive lipid profiling was performed on gastrocnemius muscles harvested from lean and obese Zucker rats immediately and 25 min after 15 min of one-legged electrically stimulated contraction compared with the contralateral control (rested) limbs. Predictably, IMTG content was grossly elevated in control muscles from obese rats compared with their lean counterparts. In muscles of obese (but not lean) rats, contraction resulted in marked hydrolysis of IMTG, which was then restored to near resting levels during 25 min of recovery. Despite dramatic phenotypical differences in contraction-induced IMTG turnover, muscle levels of diacylglycerol (DAG) and long-chain acyl-CoAs (LCACoA) were surprisingly similar between groups. Tissue profiles of acylcarnitine metabolites suggested that the surfeit of IMTG in obese rats fueled higher rates of fat oxidation relative to the lean group. Muscles of the obese rats had reduced lactate levels immediately following contraction and higher glycogen resynthesis during recovery, consistent with a lipid-associated glucose-sparing effect. Together, these findings suggest that contraction-induced mobilization of local lipid reserves in obese muscles promotes beta-oxidation, while discouraging glucose utilization. Further studies are necessary to determine whether persistent oxidation of IMTG-derived fatty acids contributes to systemic glucose intolerance in other physiological settings.

Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton.

PubMed

Liu, Li-Bo; Xue, Yi-Xue; Liu, Yun-Hui; Wang, Yi-Bao

2008-04-01

Bradykinin (BK) has been shown to open blood-tumor barrier (BTB) selectively and to increase permeability of the BTB transiently, but the mechanism is unclear. This study was performed to determine whether BK opens the BTB by affecting the tight junction (TJ)-associated proteins zonula occluden-1 (ZO-1), occludin, and caludin-5 and cytoskeleton protein filamentous actin (F-actin). In rat brain glioma model and BTB model in vitro, we find that the protein expression levels of ZO-1, occludin, and claudin-5 are attenuated by BK induction. Immunohistochemistry and immunofluorescence assays show that the attenuated expression of ZO-1, occludin, and claudin-5 and F-actin is most obvious in the smaller tumor capillaries (<20 microm) after BK infusion, and there is no change in the larger tumor capillaries (>20 microm). The redistribution of ZO-1, occludin, and claudin-5 and rearrangement of F-actin in brain microvascular endothelial cells are observed at the same time. Meanwhile, Evans blue assay shows that the permeability of BTB increases after BK infusion. Transmission electron microscopy indicates that TJ is opened and that pinocytotic vesicular density is increased. Transendothelial electrical resistance (TEER) and horseradish peroxidase flux assays also reveal that TJ is opened by BK induction. In addition, radioimmunity and Western blot assay reveal a significant decrease in expression levels of cAMP and catalytic subunit of protien kinase A (PKAcs) of tumor tissue. This study demonstrates that the increase of BK-mediated BTB permeability is associated with the down-regulation of ZO-1, occludin, and claudin-5 and the rearrangement of F-actin and that cAMP/PKA signal transduction system might be involved in the modulating process.

Study of the regulation by nutrients of the expression of genes involved in lipogenesis and obesity in humans and animals.

PubMed

Delzenne, N; Ferré, P; Beylot, M; Daubioul, C; Declercq, B; Diraison, F; Dugail, I; Foufelle, F; Foretz, M; Mace, K; Reimer, R; Palmer, G; Rutter, G; Tavare, J; Van Loo, J; Vidal, H

2001-08-01

Dietary digestible carbohydrates are able to modulate lipogenesis, by modifying the expression of genes coding for key lipogenic enzymes, like fatty acid synthase. The overall objective of the Nutrigene project (FAIR-CT97-3011) was to study the efficiency of various carbohydrates to modulate the lipogenic capacity and relevant gene expression in rat and human species (control and obese subjects) and to understand the underlying molecular mechanisms involved in the regulation of lipogenic genes by carbohydrates. Key cellular mediators (namely SREBP-1c and 2, AMP activated protein kinase, cholesterol content) of the regulation of lipogenic gene expression by glucose and/or insulin were identified and constitute new putative targets in the development of plurimetabolic syndrome associated with obesity. In humans, hepatic lipogenesis and triglyceride synthesis, assessed in vivo by the use of stable isotopes, was promoted by a high-carbohydrate diet in non obese subjects, and in non alcoholic steatotic patients, but was not modified in the adipose tissue of obese subjects. Non digestible/fermentable carbohydrates, such as fructans, were shown to decrease hepatic lipogenesis in non obese rats, and to lessen hepatic steatosis and body weight in obese Zucker rats. If confirmed in obese humans, this would allow the development of functional food able to counteract the metabolic disturbances linked to obesity.

Effects of a-high- and low-diadzein diet on liver steatosis and serum adipokines in female obese Zucker rats

USDA-ARS?s Scientific Manuscript database

Rates of obesity worldwide are increasing. Obesity is associated with adipokine dysregulation and insulin resistance, which are factors that increase the risk of developing chronic diseases. As such, the risk for non-alcoholic fatty liver disease (NAFLD) markedly increases in the presence of obesity...

Obesity-induced hepatic hypoperfusion primes for hepatic dysfunction after resuscitated hemorrhagic shock.

PubMed

Matheson, Paul J; Hurt, Ryan T; Franklin, Glen A; McClain, Craig J; Garrison, R Neal

2009-10-01

Obese patients (BMI>35) after blunt trauma are at increased risk compared to non-obese for organ dysfunction, prolonged hospital stay, infection, prolonged mechanical ventilation, and mortality. Obesity and non-alcoholic fatty liver disease (NAFLD) produce a low grade systemic inflammatory response syndrome (SIRS) with compromised hepatic blood flow, which increases with body mass index. We hypothesized that obesity further aggravates liver dysfunction by reduced hepatic perfusion following resuscitated hemorrhagic shock (HEM). Age-matched Zucker rats (Obese, 314-519 g & Lean, 211-280 g) were randomly assigned to 4 groups (n = 10-12/group): (1) Lean-Sham; (2) Lean, HEM, and resuscitation (HEM/RES); (3) Obese-Sham; and (4) Obese-HEM/RES. HEM was 40% of mean arterial pressure (MAP) for 60 min; RES was return of shed blood/5 min and 2 volumes of saline/25 min. Hepatic blood flow (HBF) using galactose clearance, liver enzymes and complete metabolic panel were measured over 4 h after completion of RES. Obese rats had increased MAP, heart rate, and fasting blood glucose and BUN concentrations compared to lean controls, required less blood withdrawal (mL/g) to maintain 40% MAP, and RES did not restore BL MAP. Obese rats had decreased HBF at BL and during HEM/RES, which persisted 4 h post RES. ALT and BUN were increased compared to Lean-HEM/RES at 4 h post-RES. These data suggest that obesity significantly contributes to trauma outcomes through compromised vascular control or through fat-induced sinusoidal compression to impair hepatic blood flow after HEM/RES resulting in a greater hepatic injury. The pro-inflammatory state of NAFLD seen in obesity appears to prime the liver for hepatic ischemia after resuscitated hemorrhagic shock, perhaps intensified by insidious and ongoing hepatic hypoperfusion established prior to the traumatic injury or shock.

40 CFR 721.1750 - 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium salts. 721.1750 Section 721.1750... 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium...-tyl-oxy)-, sodium salt (PMN P-92-35), and 1H-benzotriazole, 5-(pentyloxy)- , potassium salt (PMN P-92...

40 CFR 721.1750 - 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium salts. 721.1750 Section 721.1750... 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium...-tyl-oxy)-, sodium salt (PMN P-92-35), and 1H-benzotriazole, 5-(pentyloxy)- , potassium salt (PMN P-92...

40 CFR 721.1750 - 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium salts. 721.1750 Section 721.1750... 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium...-tyl-oxy)-, sodium salt (PMN P-92-35), and 1H-benzotriazole, 5-(pentyloxy)- , potassium salt (PMN P-92...

40 CFR 721.1750 - 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium salts. 721.1750 Section 721.1750... 1H-Benzotriazole, 5-(pen-tyl-oxy)- and 1H-ben-zo-tri-a-zole, 5-(pen-tyl-oxy)-, sodium and potassium...-tyl-oxy)-, sodium salt (PMN P-92-35), and 1H-benzotriazole, 5-(pentyloxy)- , potassium salt (PMN P-92...

Restoration of euglycemia after duodenal bypass surgery is reliant on central and peripheral inputs in Zucker fa/fa rats.

PubMed

Jiao, Jian; Bae, Eun Ju; Bandyopadhyay, Gautam; Oliver, Jason; Marathe, Chaitra; Chen, Michael; Hsu, Jer-Yuan; Chen, Yu; Tian, Hui; Olefsky, Jerrold M; Saberi, Maziyar

2013-04-01

Gastrointestinal bypass surgeries that result in rerouting and subsequent exclusion of nutrients from the duodenum appear to rapidly alleviate hyperglycemia and hyperinsulinemia independent of weight loss. While the mechanism(s) responsible for normalization of glucose homeostasis remains to be fully elucidated, this rapid normalization coupled with the well-known effects of vagal inputs into glucose homeostasis suggests a neurohormonally mediated mechanism. Our results show that duodenal bypass surgery on obese, insulin-resistant Zucker fa/fa rats restored insulin sensitivity in both liver and peripheral tissues independent of body weight. Restoration of normoglycemia was attributable to an enhancement in key insulin-signaling molecules, including insulin receptor substrate-2, and substrate metabolism through a multifaceted mechanism involving activation of AMP-activated protein kinase and downregulation of key regulatory genes involved in both lipid and glucose metabolism. Importantly, while central nervous system-derived vagal nerves were not essential for restoration of insulin sensitivity, rapid normalization in hepatic gluconeogenic capacity and basal hepatic glucose production required intact vagal innervation. Lastly, duodenal bypass surgery selectively altered the tissue concentration of intestinally derived glucoregulatory hormone peptides in a segment-specific manner. The present data highlight and support the significance of vagal inputs and intestinal hormone peptides toward normalization of glucose and lipid homeostasis after duodenal bypass surgery.

Dipeptidylpeptidase-IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats

PubMed Central

Tarantola, E.; Bertone, V.; Milanesi, G.; Capelli, E.; Ferrigno, A.; Neri, D.; Vairetti, M.; Barni, S.; Freitas, I.

2012-01-01

Given the scarcity of donors, moderately fatty livers (FLs) are currently being considered as possible grafts for orthotopic liver transplantation (OLT), notwithstanding their poor tolerance to conventional cold preservation. The behaviour of parenchymal and sinusoidal liver cells during transplantation is being studied worldwide. Much less attention has been paid to the biliary tree, although this is considered the Achille's heel even of normal liver transplantation. To evaluate the response of the biliary compartment of FLs to the various phases of OLT reliable markers are necessary. Previously we demonstrated that Alkaline Phosphatase was scarcely active in bile canaliculi of FLs and thus ruled it out as a marker. As an alternative, dipeptidylpeptidase-IV (DPP-IV), was investigated. This ecto-peptidase plays an important role in glucose metabolism, rapidly inactivating insulin secreting hormones (incretins) that are important regulators of glucose metabolism. DPP-IV inhibitors are indeed used to treat Type II diabetes. Neuropeptides regulating bile transport and composition are further important substrates of DPP-IV in the enterohepatic axis. DPP-IV activity was investigated with an azo-coupling method in the liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. Protein expression was studied by immunofluorescence with the monoclonal antibody (clone 5E8). In Wistar rat liver, DPP-IV activity and expression were high in the whole biliary tree, and moderate in sinusoid endothelial cells, in agreement with the literature. Main substrates of DPP-IV in hepatocytes and cholangiocytes could be incretins GLP-1 and GIP, and neuropeptides such as vasoactive intestinal peptide (VIP) and substance P, suggesting that these substances are inactivated or modified through the biliary route. In lean Zucker rat liver the enzyme reaction and protein expression patterns were similar to those of Wistar rat. In obese rat liver the patterns

Dipeptidylpeptidase--IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats.

PubMed

Tarantola, E; Bertone, V; Milanesi, G; Capelli, E; Ferrigno, A; Neri, D; Vairetti, M; Barni, S; Freitas, I

2012-10-08

Given the scarcity of donors, moderately fatty livers (FLs) are currently being considered as possible grafts for orthotopic liver transplantation (OLT), notwithstanding their poor tolerance to conventional cold preservation. The behaviour of parenchymal and sinusoidal liver cells during transplantation is being studied worldwide. Much less attention has been paid to the biliary tree, although this is considered the Achille's heel even of normal liver transplantation. To evaluate the response of the biliary compartment of FLs to the various phases of OLT reliable markers are necessary. Previously we demonstrated that Alkaline Phosphatase was scarcely active in bile canaliculi of FLs and thus ruled it out as a marker. As an alternative, dipeptidylpeptidase-IV (DPP-IV), was investigated. This ecto-peptidase plays an important role in glucose metabolism, rapidly inactivating insulin secreting hormones (incretins) that are important regulators of glucose metabolism. DPP-IV inhibitors are indeed used to treat Type II diabetes. Neuropeptides regulating bile transport and composition are further important substrates of DPP-IV in the enterohepatic axis. DPP-IV activity was investigated with an azo-coupling method in the liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. Protein expression was studied by immunofluorescence with the monoclonal antibody (clone 5E8). In Wistar rat liver, DPP-IV activity and expression were high in the whole biliary tree, and moderate in sinusoid endothelial cells, in agreement with the literature. Main substrates of DPP-IV in hepatocytes and cholangiocytes could be incretins GLP-1 and GIP, and neuropeptides such as vasoactive intestinal peptide (VIP) and substance P, suggesting that these substances are inactivated or modified through the biliary route. In lean Zucker rat liver the enzyme reaction and protein expression patterns were similar to those of Wistar rat. In obese rat liver the patterns

ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway

PubMed Central

Domínguez-Calderón, Alaide; Ávila-Flores, Antonia; Ponce, Arturo; López-Bayghen, Esther; Calderón-Salinas, José-Víctor; Luis Reyes, José; Chávez-Munguía, Bibiana; Segovia, José; Angulo, Carla; Ramírez, Leticia; Gallego-Gutiérrez, Helios; Alarcón, Lourdes; Martín-Tapia, Dolores; Bautista-García, Pablo; González-Mariscal, Lorenza

2016-01-01

Renal compensatory hypertrophy (RCH) restores normal kidney function after disease or loss of kidney tissue and is characterized by an increase in organ size due to cell enlargement and not to cell proliferation. In MDCK renal epithelial cells, silencing of the tight junction protein zona occludens 2 (ZO-2 KD) induces cell hypertrophy by two mechanisms: prolonging the time that cells spend at the G1 phase of the cell cycle due to an increase in cyclin D1 level, and augmenting the rate of protein synthesis. The latter is triggered by the nuclear accumulation and increased transcriptional activity of Yes-associated protein (YAP), the main target of the Hippo pathway, which results in decreased expression of phosphatase and tensin homologue. This in turn increased the level of phosphatidylinositol (3,4,5)-triphosphate, which transactivates the Akt/mammalian target of rapamycin pathway, leading to activation of the kinase S6K1 and increased synthesis of proteins and cell size. In agreement, in a rat model of uninephrectomy, RCH is accompanied by decreased expression of ZO-2 and nuclear expression of YAP. Our results reveal a novel role of ZO-2 as a modulator of cell size. PMID:27009203

Azilsartan improves glycemic status and reduces kidney damage in zucker diabetic fatty rats.

PubMed

Hye Khan, Md Abdul; Neckář, Jan; Haines, Jasmine; Imig, John D

2014-08-01

Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats. ZDF rats were treated with vehicle or AZL-M for 8 weeks. Zucker diabetic lean (ZDL) rats were used as controls. Urine and plasma samples were collected for biochemical analysis, and kidney tissues were used for histopathological and immunohistopathological examination at the end of the 8-week protocol. ZDF rats were diabetic with hyperglycemia and impaired glucose tolerance, and AZL-M ameliorated the diabetic phenotype. ZDF rats were hypertensive compared with ZDL rats (181±6 vs. 129±7mm Hg), and AZL-M decreased blood pressure in ZDF rats (116±7mm Hg). In ZDF rats, there was marked renal damage with elevated proteinuria, albuminuria, nephrinuria, 2-4-fold higher tubular cast formation, and glomerular injury compared with ZDL rats. AZL-M treatment reduced renal damage in ZDF rats. ZDF rats demonstrated renal inflammation and oxidative stress with elevated urinary monocyte chemoattractant protein 1 excretion, renal infiltration of macrophages, and elevated kidney malondialdehyde levels. AZL-M reduced oxidative stress and inflammation in ZDF rats. Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Behavioural, morphological and electrophysiological assessment of the effects of type 2 diabetes mellitus on large and small nerve fibres in Zucker diabetic fatty, Zucker lean and Wistar rats.

PubMed

Garcia-Perez, E; Schönberger, T; Sumalla, M; Stierstorfer, B; Solà, R; Doods, H; Serra, J; Gorodetskaya, N

2018-04-20

Peripheral neuropathy is a common complication in type 2 diabetes mellitus (T2DM). The most common presentation is in the form of a distal axonal sensory-motor polyneuropathy that involves large and small nerve fibres in variable proportion. Zucker Diabetic Fatty (ZDF), Zucker Lean (ZL) and Wistar Han (WH) rats were used to assess the behavioural, morphological and electrophysiological effects that T2DM have on peripheral large and small nerve fibres of 6- to 40-week-old rats. ZDF rats presented mechanical hypersensitivity that initially worsened in parallel to the progression of diabetes and eventually reverted at later stages of the disease. The reversal from hypersensitivity to hyposensitivity paralleled a reduction in the number of intraepithelial skin nerve terminals and in the nerve fibre lengths. However, no increased levels of degeneration of dorsal root ganglion neurons were observed. Nerve conduction studies showed a reduction in sensory and motor nerve conduction velocity (CV) in hyperglycaemic ZDF rats. Microneurography showed significant alterations in several parameters of activity-dependent slowing (ADS) of mechano-insensitive C-nociceptors in ZDF rats. Surprisingly, some of these changes were also observed in ZL rats. Moreover, we found spontaneous activity in all three strains implying that C-nociceptors become hyperexcitable and spontaneously active not only in ageing hyperglycaemic ZDF rats but also in age-matched and apparently normoglycaemic ZL and WH rats fed with the same diet. ZDF rats presented a diabetic neuropathy involving large and small nerve fibres; additionally, ZL and WH rats also showed early small abnormalities in C-fibres, clearly detected by microneurography SIGNIFICANCE: This study provides a functional description of large and small nerve fibre function in a diabetic model that recapitulates many of the findings observed in patients suffering from type 2 diabetes mellitus. © 2018 European Pain Federation - EFIC®.

Emergence of an Out-of-Plane Optical Phonon (ZO) Kohn Anomaly in Quasifreestanding Epitaxial Graphene.

PubMed

Politano, Antonio; de Juan, Fernando; Chiarello, Gennaro; Fertig, Herbert A

2015-08-14

In neutral graphene, two prominent cusps known as Kohn anomalies are found in the phonon dispersion of the highest optical phonon at q=Γ (LO branch) and q=K (TO branch), reflecting a significant electron-phonon coupling (EPC) to undoped Dirac electrons. In this work, high-resolution electron energy loss spectroscopy is used to measure the phonon dispersion around the Γ point in quasifreestanding graphene epitaxially grown on Pt(111). The Kohn anomaly for the LO phonon is observed at finite momentum q~2k_{F} from Γ, with a shape in excellent agreement with the theory and consistent with known values of the EPC and the Fermi level. More strikingly, we also observe a Kohn anomaly at the same momentum for the out-of-plane optical phonon (ZO) branch. This observation is the first direct evidence of the coupling of the ZO mode with Dirac electrons, which is forbidden for freestanding graphene but becomes allowed in the presence of a substrate. Moreover, we estimate the EPC to be even greater than that of the LO mode, making graphene on Pt(111) an optimal system to explore the effects of this new coupling in the electronic properties.

Protein source in a high-protein diet modulates reductions in insulin resistance and hepatic steatosis in fa/fa Zucker rats.

PubMed

Wojcik, Jennifer L; Devassy, Jessay G; Wu, Yinghong; Zahradka, Peter; Taylor, Carla G; Aukema, Harold M

2016-01-01

High-protein diets are being promoted to reduce insulin resistance and hepatic steatosis in metabolic syndrome. Therefore, the effect of protein source in high-protein diets on reducing insulin resistance and hepatic steatosis was examined. Fa/fa Zucker rats were provided normal-protein (15% of energy) casein, high-protein (35% of energy) casein, high-protein soy, or high-protein mixed diets with animal and plant proteins. The high-protein mixed diet reduced area under the curve for insulin during glucose tolerance testing, fasting serum insulin and free fatty acid concentrations, homeostatic model assessment index, insulin to glucose ratio, and pancreatic islet cell area. The high-protein mixed and the high-protein soy diets reduced hepatic lipid concentrations, liver to body weight ratio, and hepatic steatosis rating. These improvements were observed despite no differences in body weight, feed intake, or adiposity among high-protein diet groups. The high-protein casein diet had minimal benefits. A high-protein mixed diet was the most effective for modulating reductions in insulin resistance and hepatic steatosis independent of weight loss, indicating that the source of protein within a high-protein diet is critical for the management of these metabolic syndrome parameters. © 2015 The Obesity Society.

40 CFR 721.1735 - Alkylbisoxyalkyl (sub-sti-tut-ed-1,1-dimethylethylphenyl) ben-zo-tria-zole (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1735 Alkylbisoxyalkyl (sub-sti-tut-ed-1,1-dimethylethylphenyl) ben-zo-tria-zole (generic name). (a) Chemical substance and significant new...

Dysregulation of glucocorticoid metabolism in murine obesity: comparable effects of leptin resistance and deficiency.

PubMed

Livingstone, Dawn E W; Grassick, Sarah L; Currie, Gillian L; Walker, Brian R; Andrew, Ruth

2009-05-01

In obese humans, metabolism of glucocorticoids by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) and A-ring reduction (by 5 alpha- and 5 beta-reductases) is dysregulated in a tissue specific manner. These changes have been recapitulated in leptin resistant obese Zucker rats but were not observed in high-fat fed Wistar rats. Recent data from mouse models suggest that such discrepancies may reflect differences in leptin signalling. We therefore compared glucocorticoid metabolism in murine models of leptin deficiency and resistance. Male ob/ob and db/db mice and their respective littermate controls (n=10-12/group) were studied at the age of 12 weeks. Enzyme activities and mRNA expression were quantified in snap-frozen tissues. The patterns of altered pathways of steroid metabolism in obesity were similar in ob/ob and db/db mice. In liver, 5 beta-reductase activity and mRNA were increased and 11 beta-HSD1 decreased in obese mice, whereas 5 alpha-reductase 1 (5 alpha R1) mRNA was not altered. In visceral adipose depots, 5 beta-reductase was not expressed, 11 beta-HSD1 activity was increased and 5 alpha R1 mRNA was not altered in obesity. By contrast, in subcutaneous adipose tissue 11 beta-HSD1 and 5 alpha R1 mRNA were decreased. Systematic differences were not found between ob/ob and db/db murine models of obesity, suggesting that variations in leptin signalling through the short splice variant of the Ob receptor do not contribute to dysregulation of glucocorticoid metabolism.

MiR-18a increased the permeability of BTB via RUNX1 mediated down-regulation of ZO-1, occludin and claudin-5.

PubMed

Miao, Yin-Sha; Zhao, Ying-Yu; Zhao, Li-Ni; Wang, Ping; Liu, Yun-Hui; Ma, Jun; Xue, Yi-Xue

2015-01-01

The purposes of this study were to investigate the possible molecular mechanisms of miR-18a regulating the permeability of blood-tumor barrier (BTB) via down-regulated expression and distribution of runt-related transcription factor 1 (RUNX1). An in vitro BTB model was established with hCMEC/D3 cells and U87MG cells to obtain glioma vascular endothelial cells (GECs). The endogenous expressions of miR-18a and RUNX1 were converse in GECs. The overexpression of miR-18a significantly impaired the integrity and increased the permeability of BTB, which respectively were detected by TEER and HRP flux assays, accompanied by down-regulated mRNA and protein expressions and distributions of ZO-1, occludin and claudin-5 in GECs. Dual-luciferase reporter assay was carried out and revealed RUNX1 is a target gene of miR-18a. Meanwhile, mRNA and protein expressions and distribution of RUNX1 were downregulated by miR-18a. Most important, miR-18a and RUNX1 could reversely regulate the permeability of BTB as well as the expressions and distributions of ZO-1, occludin and claudin-5. Finally, chromatin immunoprecipitation verified that RUNX1 interacted with "TGGGGT" DNA sequence in promoter region of ZO-1, occludin and claudin-5 respectively. Taken together, our present study indicated that miR-18a increased the permeability of BTB via RUNX1 mediated down-regulation of tight junction related proteins ZO-1, occludin and claudin-5, which would attract more attention to miR-18a and RUNX1 as potential targets of drug delivery across BTB and provide novel strategies for glioma treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity.

PubMed

Zvejniece, Liga; Svalbe, Baiba; Vavers, Edijs; Makrecka-Kuka, Marina; Makarova, Elina; Liepins, Vilnis; Kalvinsh, Ivars; Liepinsh, Edgars; Dambrova, Maija

2017-09-01

S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents. Copyright © 2017. Published by Elsevier Inc.

Body weight-dependent troponin T alternative splicing is evolutionarily conserved from insects to mammals and is partially impaired in skeletal muscle of obese rats.

PubMed

Schilder, Rudolf J; Kimball, Scot R; Marden, James H; Jefferson, Leonard S

2011-05-01

Do animals know at a physiological level how much they weigh, and, if so, do they make homeostatic adjustments in response to changes in body weight? Skeletal muscle is a likely tissue for such plasticity, as weight-bearing muscles receive mechanical feedback regarding body weight and consume ATP in order to generate forces sufficient to counteract gravity. Using rats, we examined how variation in body weight affected alternative splicing of fast skeletal muscle troponin T (Tnnt3), a component of the thin filament that regulates the actin-myosin interaction during contraction and modulates force output. In response to normal growth and experimental body weight increases, alternative splicing of Tnnt3 in rat gastrocnemius muscle was adjusted in a quantitative fashion. The response depended on weight per se, as externally attached loads had the same effect as an equal change in actual body weight. Examining the association between Tnnt3 alternative splicing and ATP consumption rate, we found that the Tnnt3 splice form profile had a significant association with nocturnal energy expenditure, independently of effects of weight. For a subset of the Tnnt3 splice forms, obese Zucker rats failed to make the same adjustments; that is, they did not show the same relationship between body weight and the relative abundance of five Tnnt3 β splice forms (i.e. Tnnt3 β2-β5 and β8), four of which showed significant effects on nocturnal energy expenditure in Sprague-Dawley rats. Heavier obese Zucker rats displayed certain splice form relative abundances (e.g. Tnnt3 β3) characteristic of much lighter, lean animals, resulting in a mismatch between body weight and muscle molecular composition. Consequently, we suggest that body weight-inappropriate skeletal muscle Tnnt3 expression in obesity is a candidate mechanism for muscle weakness and reduced mobility. Weight-dependent quantitative variation in Tnnt3 alternative splicing appears to be an evolutionarily conserved feature of

A diet containing a high- versus low-daidzein level does not protect against liver steatosis in the obese Zucker rat model

USDA-ARS?s Scientific Manuscript database

The prevalence of obesity is increasing worldwide. Obesity increases the risk for non-alcoholic fatty liver disease through adipokine dysregulation and inflammation. Previously, we reported a high-isoflavone soy protein isolate (HISPI) diet was associated with significantly heavier body weights and ...

Circulating adiponectin concentrations are increased by dietary resistant starch and correlate with serum 25-hydroxycholecalciferol concentrations and kidney function in Zucker diabetic fatty rats.

PubMed

Koh, Gar Yee; Derscheid, Rachel; Fuller, Kelly N Z; Valentine, Rudy J; Leow, Shu En; Reed, Leah; Wisecup, Emily; Schalinske, Kevin L; Rowling, Matthew J

2016-04-01

We previously reported that dietary resistant starch (RS) type 2 prevented proteinuria and promoted vitamin D balance in type 2 diabetic (T2D) rats. Here, our primary objective was to identify potential mechanisms that could explain our earlier observations. We hypothesized that RS could promote adiponectin secretion and regulate the renin-angiotensin system activity in the kidney. Lean Zucker rats (n = 5) were fed control diet; Zucker diabetic fatty rats (n = 5/group) were fed either an AIN-93G control diet (DC) or AIN-93G diet containing either 10% RS or 20% RS (HRS) for 6 weeks. Resistant starch had no impact on blood glucose concentrations and hemoglobin A1c percentage, yet circulating adiponectin was 77% higher in HRS-fed rats, compared to DC rats. Adiponectin concentrations strongly correlated with serum 25-hydroxycholecalciferol (r = 0.815; P < .001) and urinary creatinine concentrations (r = 0.818; P < .001) and inversely correlated with proteinuria (r = -0.583; P = .02). Serum angiotensin II concentrations were 44% lower, and expression of the angiotensin II receptor, type 1, was attenuated in RS-fed rats. Moreover, we observed a 14-fold increase in messenger RNA expression of nephrin, which is required for functioning of the renal filtration barrier, in HRS rats. The HRS, but not 10% RS diet, increased circulating 25-hydroxycholecalciferol concentrations and attenuated urinary loss of vitamin D metabolites in Zucker diabetic fatty rats. Taken together, we provide evidence that vitamin D balance in the presence of hyperglycemia is strongly associated with serum adiponectin levels and reduced renal renin-angiotensin system signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression of ZO-1 and claudin-1 in a 3D epidermal equivalent using canine progenitor epidermal keratinocytes.

PubMed

Teramoto, Keiji; Asahina, Ryota; Nishida, Hidetaka; Kamishina, Hiroaki; Maeda, Sadatoshi

2018-05-21

Previous studies indicate that tight junctions are involved in the pathogenesis of canine atopic dermatitis (cAD). An in vitro skin model is needed to elucidate the specific role of tight junctions in cAD. A 3D epidermal equivalent model using canine progenitor epidermal keratinocytes (CPEK) has been established; the expression of tight junctions within this model is uncharacterized. To investigate the expression of tight junctions in the 3D epidermal equivalent. Two normal laboratory beagle dogs served as donors of full-thickness skin biopsy samples for comparison to the in vitro model. Immunohistochemical techniques were employed to investigate the expression of tight junctions including zonula occludens (ZO)-1 and claudin-1 in normal canine skin, and in the CPEK 3D epidermal equivalent. Results demonstrated the expression of ZO-1 and claudin-1 in the CPEK 3D epidermal equivalent, with staining patterns that were similar to those in normal canine skin. The CPEK 3D epidermal equivalent has the potential to be a suitable in vitro research tool for clarifying the specific role of tight junctions in cAD. © 2018 ESVD and ACVD.

Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

PubMed

Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

2014-12-02

Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Plekhs1 and Prdx3 are candidate genes responsible for mild hyperglycemia associated with obesity in a new animal model of F344-fa-nidd6 rat.

PubMed

Kotoh, Jun; Sasaki, Daiki; Matsumoto, Kozo; Maeda, Akihiko

2016-12-01

Type 2 diabetes is a polygenic disease and characterized by hyperglycemia and insulin resistance, and it is strongly associated with obesity. However, the mechanism by which obesity contributes to onset of type 2 diabetes is not well understood. We generated rat strains with a hyperglycemic quantitative trait locus (QTL) derived from the Otsuka Long-Evans Tokushima Fatty rat and a fa/fa (Lepr -/- ) locus derived from the Zucker Fatty rat. Phenotypes for plasma glucose, and insulin levels were measured, and RNA and protein levels were determined using reverse transcription quantitative PCR and Western blot analyses, respectively. Compared with the obese control strain F344-fa (Lepr -/- ), plasma glucose levels of the obese F344-fa-nidd6 (Lepr -/- and Nidd6/of) significantly increased, and plasma insulin levels significantly decreased. These phenotypes were not observed in the lean strains, suggesting that the Nidd6/of locus harbors a diabetogenic gene associated with obesity. We measured the expression of 41 genes in the Nidd6/of QTL region of each strain and found that the mRNA expression levels of the two genes significantly differed between the obese strains. The two genes, pleckstrin homology domain-containing, family S member 1 (Plechs1) and peroxiredoxin III (Prdx3), were differentially expressed only in the obese rats, suggesting that these two genes are involved in the mild elevation of blood glucose levels and insulin resistance in obesity.

Proliferative endocrine effects of adipose tissue from obese animals on MCF7 cells are ameliorated by resveratrol supplementation.

PubMed

Theriau, Christopher F; Sauvé, O'Llenecia S; Beaudoin, Marie-Soleil; Wright, David C; Connor, Michael K

2017-01-01

Obesity is clearly associated with an increased risk of breast cancer in postmenopausal women. The purpose was to determine if obesity alters the adipocyte adipokine secretion profile, thereby altering the adipose-dependent paracrine/endocrine growth microenvironment surrounding breast cancer cells (MCF7). Additionally, we determined whether resveratrol (RSV) supplementation can counteract any obesity-dependent effects on breast cancer tumor growth microenvironment. Obese ZDF rats received standard chow diet or diet supplemented with 200 mg/kg body weight RSV. Chow-fed Zucker rats served as lean controls. After 6 weeks, conditioned media (CM) prepared from inguinal subcutaneous adipose tissue (scAT) was added to MCF7 cells for 24 hrs. Experiments were also conducted using purified isolated adipocytes to determine whether any endocrine effects could be attributed specifically to the adipocyte component of adipose tissue. scAT from ZDF rats promoted cell cycle entry in MCF7 cells which was counteracted by RSV supplementation. RSV-CM had a higher ratio of ADIPO:LEP compared to ZDF-CM. This altered composition of the CM led to increased levels of pAMPKT172, p27, p27T198 and AdipoR1 while decreasing pAktT308 in MCF7 cells grown in RSV-CM compared to ZDF-CM. RSV-CM increased number of cells in G0/G1 and decreased cells in S-phase compared to ZDF-CM. Co-culture experiments revealed that these obesity-dependent effects were driven by the adipocyte component of the adipose tissue. Obesity decreased the ratio of adiponectin:leptin secreted by adipocytes, altering the adipose-dependent growth microenvironment resulting in increased breast cancer cell proliferation. Supplementation with RSV reversed these adipose-dependent effects suggesting a potential for RSV as a nutritional supplementation to improve breast cancer treatment in obese patients.

Brown Norway and Zucker Lean Rats Demonstrate Circadian Variation in Ventilation and Sleep Apnea

PubMed Central

Fink, Anne M.; Topchiy, Irina; Ragozzino, Michael; Amodeo, Dionisio A.; Waxman, Jonathan A.; Radulovacki, Miodrag G.; Carley, David W.

2014-01-01

Study Objectives: Circadian rhythms influence many biological systems, but there is limited information about circadian and diurnal variation in sleep related breathing disorder. We examined circadian and diurnal patterns in sleep apnea and ventilatory patterns in two rat strains, one with high sleep apnea propensity (Brown Norway [BN]) and the other with low sleep apnea propensity (Zucker Lean [ZL]). Design/Setting: Chronically instrumented rats were randomized to breathe room air (control) or 100% oxygen (hyperoxia), and we performed 20-h polysomnography beginning at Zeitgeber time 4 (ZT 4; ZT 0 = lights on, ZT12 = lights off). We examined the effect of strain and inspired gas (twoway analysis of variance) and analyzed circadian and diurnal variability. Measurements and Results: Strain and inspired gas-dependent differences in apnea index (AI; apneas/h) were particularly prominent during the light phase. AI in BN rats (control, 16.9 ± 0.9; hyperoxia, 34.0 ± 5.8) was greater than in ZL rats (control, 8.5 ± 1.0; hyperoxia, 15.4 ± 1.1, [strain effect, P < 0.001; gas effect, P = 0.001]). Hyperoxia reduced respiratory frequency in both strains, and all respiratory pattern variables demonstrated circadian variability. BN rats exposed to hyperoxia demonstrated the largest circadian fluctuation in AI (amplitude = 17.9 ± 3.7 apneas/h [strain effect, P = 0.01; gas effect, P < 0.001; interaction, P = 0.02]; acrophase = 13.9 ± 0.7 h; r2 = 0.8 ± 1.4). Conclusions: Inherited, environmental, and circadian factors all are important elements of underlying sleep related breathing disorder. Our method to examine sleep related breathing disorder phenotypes in rats may have implications for understanding vulnerability for sleep related breathing disorder in humans. Citation: Fink AM; Topchiy I; Ragozzino M; Amodeo DA; Waxman JA; Radulovacki MG; Carley DW. Brown Norway and Zucker Lean rats demonstrate circadian variation in ventilation and sleep apnea. SLEEP 2014

Effects of a diabetes-specific enteral nutrition on nutritional and immune status of diabetic, obese, and endotoxemic rats: interest of a graded arginine supply.

PubMed

Breuillard, Charlotte; Darquy, Sylviane; Curis, Emmanuel; Neveux, Nathalie; Garnier, Jean-Pierre; Cynober, Luc; De Bandt, Jean-Pascal

2012-08-01

Obese and type 2 diabetic patients present metabolic disturbance-related alterations in nonspecific immunity, to which the decrease in their plasma arginine contributes. Although diabetes-specific formulas have been developed, they have never been tested in the context of an acute infectious situation as can be seen in intensive care unit patients. Our aim was to investigate the effects of a diabetes-specific diet enriched or not with arginine in a model of infectious stress in a diabetes and obesity situation. As a large intake of arginine may be deleterious, this amino acid was given in graded fashion. Randomized, controlled experimental study. University research laboratory. Zucker diabetic fatty rats. Gastrostomized Zucker diabetic fatty rats were submitted to intraperitoneal lipopolysaccharide administration and fed for 7 days with either a diabetes-specific enteral nutrition without (G group, n=7) or with graded arginine supply (1-5 g/kg/day) (GA group, n=7) or a standard enteral nutrition (HP group, n=10). Survival rate was better in G and GA groups than in the HP group. On day 7, plasma insulin to glucose ratio tended to be lower in the same G and GA groups. Macrophage tumor necrosis factor-α (G: 5.0±1.1 ng/2×10⁶ cells·hr⁻¹; GA: 3.7±0.8 ng/2×10⁶ cells·hr⁻¹; and HP: 1.7±0.6 ng/2×10⁶ cells·hr⁻¹; p<.05 G vs. HP) and nitric oxide (G: 4.5±1.1 ng/2×10⁶ cells·hr⁻¹; GA: 5.1±1.0 ng/2×10⁶ cells·hr⁻¹; and HP: 1.0±0.5 nmol/2×10⁶ cells·hr⁻¹; p<.05 G and GA vs. HP) productions were higher in the G and GA groups compared to the HP group. Macrophages from the G and GA groups exhibited increased arginine consumption. In diabetic obese and endotoxemic rats, a diabetes-specific formula leads to a lower mortality, a decreased insulin resistance, and an improvement in peritoneal macrophage function. Arginine supplementation has no additional effect. These data support the use of such disease-specific diets in critically ill

Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat.

PubMed

Neff, Karl J; Elliott, Jessie A; Corteville, Caroline; Abegg, Kathrin; Boza, Camilo; Lutz, Thomas A; Docherty, Neil G; le Roux, Carel W

2017-01-01

Reductions in urinary protein excretion after Roux-en-Y gastric bypass (RYGB) surgery in patients with diabetic kidney disease have been reported in multiple studies. To determine the weight loss dependence of the effect of RYGB on urinary protein excretion by comparing renal outcomes in Zucker diabetic fatty rats undergoing either gastric bypass surgery or a sham operation with or without weight matching. University laboratories. Zucker diabetic fatty rats underwent surgery at 18 weeks of age. A subgroup of sham operated rats were weight matched to RYGB operated rats by restricting food intake. Urinary protein excretion was assessed at baseline and at postoperative weeks 4 and 12. Renal histology and macrophage-associated inflammation were assessed at postoperative week 12. Progressive urinary protein excretion was attenuated by both RYGB and diet-induced weight loss, albeit to a lesser extent by the latter. Both weight loss interventions produced equivalent reductions in glomerulomegaly, glomerulosclerosis, and evidence of renal macrophage infiltration. Weight loss per se improves renal structure and attenuates renal inflammatory responses in an experimental animal model of diabetic kidney disease. Better glycemic control post-RYGB may in part explain the greater reductions in urinary protein excretion after gastric bypass surgery. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Development of insulin resistance and endothelin-1 levels in the Zucker fatty rat.

PubMed

Berthiaume, Nathalie; Mika, Amanda K; Zinker, Bradley A

2003-07-01

In order to determine the effects of increasing insulin resistance on endothelin-1 (ET-1) levels, Zucker lean and fatty rats were studied at basal and during a complete nutrient meal tolerance test (MTT) at 7, 12, and 15 weeks of age. The fatty rats were mildly hyperglycemic, severely hyperinsulinemic and glucose-intolerant at all ages versus lean animals and this progressed with age within groups, as previously published. Basal ET-1 levels, at 7 weeks, were significantly increased in fatty versus lean rats (3.2+/-0.5 v 2.0+/-0.3 pg/mL, respectively; P<.05); however, we did not observe any significant basal difference at 12 or 15 weeks. At 7 weeks, ET-1 levels between fatty and lean rats were not different during the MTT (15 minutes: 2.9+/-0.4 v 2.7+/-0.7; 120 minutes: 6.5+/-0.8 v 6.6+/-0.5 pg/mL, fatty v lean, respectively). At 12 weeks, though there was no difference in basal levels, fatty rats had higher ET-1 levels during the MTT compared to lean animals (15 minutes: 6.9+/-1.4 v 1.8+/-0.4; 120 minutes: 9.4+/-1.7 v 3.2+/-0.5 pg/mL, respectively; P<.01). At 15 weeks, ET-1 levels during the MTT receded to levels similar to those observed at 7 weeks, which were significantly higher in fatty versus lean rats 15 minutes following the challenge (3.4+/-0.4 v 2.4+/-0.2 pg/mL, respectively; P<.05). In conclusion, ET-1 levels in the Zucker fatty rat: (1) were increased in the early stages of the progression of insulin resistance at 7 weeks, but were unchanged under basal conditions with age thereafter, and (2) were increased under nutrient challenge conditions with advanced insulin resistance up to 12 weeks, and were still significantly but to a lesser degree increased at 15 weeks of age. The explanation for these results and their relationship to the observed insulin resistance is unclear and will require further investigation.

[Effect of eicosapentaenoic acid on mRNA expression of tight junction protein ZO-1 in intestinal epithelial cells after Escherichia coli LF82 infection].

PubMed

Hao, Li-Jun; Lin, Yan; Zhang, Wei; Tian, Jiao; Wang, Ya; Chen, Peng-De; Hu, Chong-Kang; Zeng, Ling-Chao; Yang, Jie; Wang, Bao-Xi; Jiang, Xun

2017-06-01

To investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection. The Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant. After EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant inhibitory effect on the proliferation of Caco-2 cells in a dose-dependent manner. The survival rates of the cells were significantly lower than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant increase in cell apoptosis rate compared with the control group (P<0.05). The 6- and 12-hour E.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group

Feeding butter with elevated content of trans-10, cis-12 conjugated linoleic acid to obese-prone rats impairs glucose and insulin tolerance.

PubMed

Hamilton, Melissa; Hopkins, Loren E; AlZahal, Ousama; MacDonald, Tara L; Cervone, Daniel T; Wright, David C; McBride, Brian W; Dyck, David J

2015-09-28

We recently demonstrated that feeding a natural CLAt10,c12-enriched butter to lean female rats resulted in small, but significant increases in fasting glucose and insulin concentrations, and impaired insulin tolerance. Our goal was to extend these findings by utilizing the diabetes-prone female fatty Zucker rat. Rats were fed custom diets containing 45 % kcal of fat derived from control and CLAt10,c12-enriched butter for 8 weeks. CLA t10,c12-enriched butter was prepared from milk collected from cows fed a high fermentable carbohydrate diet to create subacute rumen acidosis (SARA); control (non-SARA) butter was collected from cows fed a low grain diet. Female fatty Zucker rats (10 weeks old) were randomly assigned to one of four diet treatments: i) low fat (10 % kcal), ii) 45 % kcal lard, iii) 45 % kcal SARA butter, or iv) 45 % kcal non-SARA butter. A low fat fed lean Zucker group was used as a control group. After 8 weeks, i) glucose and insulin tolerance tests, ii) insulin signaling in muscle, adipose and liver, and iii) metabolic caging measurements were performed. Glucose and insulin tolerance were significantly impaired in all fatty Zucker groups, but to the greatest extent in the LARD and SARA conditions. Insulin signaling (AKT phosphorylation) was impaired in muscle, visceral (perigonadal) adipose tissue and liver in fatty Zucker rats, but was generally similar across dietary groups. Physical activity, oxygen consumption, food intake and weight gain were also similar amongst the various fatty Zucker groups. Increasing the consumption of a food naturally enriched with CLAt10,c12 significantly worsens glucose and insulin tolerance in a diabetes-prone rodent model. This outcome is not explained by changes in tissue insulin signaling, physical activity, energy expenditure, food intake or body mass.

Can the ZoMBieS method be used to characterise scintillator non-linearity?

PubMed

Bignell, L J

2014-05-01

Measurements of the detection efficiency as a function of deposited electron energy in a liquid scintillation cocktail between 4 keV and 49 keV are obtained using the ZoMBieS method. Comparison is made between the measured data and the Poisson-Birks detection efficiency model. Measurements of the Birks non-linearity parameter, kB, and the linearised scintillation response of each photomultiplier, ω(i), were made using these data. However, the value of kB that best linearises the scintillator response is found to vary depending upon which photomultiplier is used in its determination, and the measured kB and ω(i) vary depending on the external source geometry. The cause of this behaviour is unknown. The triple-coincident detection efficiency appears to be unaffected by any systematic errors. © 2013 Published by Elsevier Ltd.

New animal models reveal that coenzyme Q2 (Coq2) and placenta-specific 8 (Plac8) are candidate genes for the onset of type 2 diabetes associated with obesity in rats.

PubMed

Sasaki, Daiki; Kotoh, Jun; Watadani, Risa; Matsumoto, Kozo

2015-12-01

Obesity is a major risk factor for the onset of type 2 diabetes; however, little is known about the gene(s) involved. Therefore, we developed new animal models of obesity to search for diabetogenic genes associated with obesity. We generated double congenic rat strains with a hyperglycaemic quantitative trait locus (QTL) derived from the Otsuka Long-Evans Tokushima Fatty rat and a fa/fa (Lepr-/-) locus derived from the Zucker Fatty rat; phenotypic analysis for plasma glucose and insulin levels and RNA and protein levels were determined using reverse transcription quantitative PCR and Western blotting analyses, respectively. The double congenic strain F344-fa-nidd2 (Lepr-/- and Nidd2/of) exhibited significantly higher glucose levels and significantly lower hypoglycaemic response to insulin than the obese control strain F344-fa (Lepr-/-). These phenotypes were clearly observed in the obese strains but not in the lean strains. These results indicate that the Nidd2/of locus harbours a diabetogenic gene associated with obesity. We measured the expression of 60 genes in the Nidd2/of QTL region between the strains and found that the mRNA expression levels of five genes were significantly different between the strains under the condition of obesity. However, three of the five genes were differentially expressed in both obese and lean rats, indicating that these genes are not specific for the condition of obesity. Conversely, the other two genes, coenzyme Q2 (Coq2) and placenta-specific 8 (Plac8), were differentially expressed only in the obese rats, suggesting that these two genes are candidates for the onset of type 2 diabetes associated with obesity in rats.

Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C.

PubMed

Cario, Elke; Gerken, Guido; Podolsky, Daniel K

2004-07-01

Protein kinase C (PKC) has been implicated in regulation of intestinal epithelial integrity in response to lumenal bacteria. Intestinal epithelial cells (IECs) constitutively express Toll-like receptor (TLR)2, which contains multiple potential PKC binding sites. The aim of this study was to determine whether TLR2 may activate PKC in response to specific ligands, thus potentially modulating barrier function in IECs. TLR2 agonist (synthetic bacterial lipopeptide Pam(3)CysSK4, peptidoglycan)-induced activation of PKC-related signaling cascades were assessed by immunoprecipitation, Western blotting, immunofluorescence, and kinase assays-combined with functional transfection studies in the human model IEC lines HT-29 and Caco-2. Transepithelial electrical resistance characterized intestinal epithelial barrier function. Stimulation with TLR2 ligands led to activation (phosphorylation, enzymatic activity, translocation) of specific PKC isoforms (PKCalpha and PKCdelta). Phosphorylation of PKC by TLR2 ligands was blocked specifically by transfection with a TLR2 deletion mutant. Ligand-induced activation of TLR2 greatly enhanced transepithelial resistance in IECs, which was prevented by pretreatment with PKC-selective antagonists. This effect correlated with apical tightening and sealing of tight junction (TJ)-associated ZO-1, which was mediated via PKC in response to TLR2 ligands, whereas morphologic changes of occludin, claudin-1, or actin cytoskeleton were not evident. Downstream the endogenous PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS), but not transcriptional factor activator protein-1 (AP-1), was activated significantly on stimulation. The present study provides evidence that PKC is an essential component of the TLR2 signaling pathway with the physiologic consequence of directly enhancing intestinal epithelial integrity through translocation of ZO-1 on activation.

Carbohydrate-Free Peach (Prunus persica) and Plum (Prunus domestica) Juice Affects Fecal Microbial Ecology in an Obese Animal Model

PubMed Central

Markel, Melissa; Martino, Hercia S.; Minamoto, Yasushi; Steiner, Jörg M.; Byrne, David; Suchodolski, Jan S.; Mertens-Talcott, Susanne U.

2014-01-01

Background Growing evidence shows the potential of nutritional interventions to treat obesity but most investigations have utilized non-digestible carbohydrates only. Peach and plum contain high amounts of polyphenols, compounds with demonstrated anti-obesity effects. The underlying process of successfully treating obesity using polyphenols may involve an alteration of the intestinal microbiota. However, this phenomenon is not well understood. Methodology/Principal Findings Obese Zucker rats were assigned to three groups (peach, plum, and control, n = 10 each), wild-type group was named lean (n = 10). Carbohydrates in the fruit juices were eliminated using enzymatic hydrolysis. Fecal samples were obtained after 11 weeks of fruit or control juice administration. Real-time PCR and 454-pyrosequencing were used to evaluate changes in fecal microbiota. Over 1,500 different Operational Taxonomic Units at 97% similarity were detected in all rats. Several bacterial groups (e.g. Lactobacillus and members of Ruminococcacea) were found to be more abundant in the peach but especially in the plum group (plum juice contained 3 times more total polyphenolics compared to peach juice). Principal coordinate analysis based on Unifrac-based unweighted distance matrices revealed a distinct separation between the microbiota of control and treatment groups. These changes in fecal microbiota occurred simultaneously with differences in fecal short-chain acids concentrations between the control and treatment groups as well as a significant decrease in body weight in the plum group. Conclusions This study suggests that consumption of carbohydrate-free peach and plum juice has the potential to modify fecal microbial ecology in an obese animal model. The separate contribution of polyphenols and non-polyphenols compounds (vitamins and minerals) to the observed changes is unknown. PMID:25007331

Leptin receptor-deficient obese Zucker rats reduce their food intake in response to a systemic supply of calories from glucose.

PubMed

Gilbert, Marc; Magnan, Christophe; Turban, Sophie; André, Jocelyne; Guerre-Millo, Michèle

2003-02-01

It has been established that leptin exerts a negative control on food intake, allowing one to maintain stable caloric intake over time. The aim of the present study was to investigate whether leptin regulates food intake when a supply of calories is provided by the systemic route. Experiments were carried out in leptin receptor-deficient obese fa/fa rats and lean Fa/fa controls. In both groups, 48 h of glucose infusion reduced food intake in proportion to caloric supply, resulting in virtually no change in total caloric intake as compared to before the infusion. This hypophagic response was reproduced without adding systemic calories, but by increasing glucose and insulin concentrations specifically in the brain through carotid artery infusion. Concomitant intracerebroventricular administration of 5-(tetradecyloxy)-2-furoic acid, an acetyl CoA carboxylase inhibitor that precludes malonyl-CoA synthesis, abolished the restriction of feeding in carotid-infused lean and obese rats. These data indicate that a supply of calories via glucose infusion induces a hypophagic response independent of leptin signaling in the rat, and support the hypothesis that a rise in central malonyl-CoA, triggered by increased glucose and insulin concentrations, participates in this adaptation. This process could contribute to the limiting of hyperphagia, primarily when leptin signaling is altered, as in the obese state.

Transcriptional alterations of ET-1 axis and DNA damage in lung tissue of a rat obesity model.

PubMed

Del Ry, Silvia; Cabiati, Manuela; Salvadori, Costanza; Guiducci, Letizia; Caselli, Chiara; Prescimone, Tommaso; Facioni, Maria Sole; Azzarà, Alessia; Chiaramonte, Anna; Mazzoni, Stefano; Bruschi, Fabrizio; Giannessi, Daniela; Scarpato, Roberto

2015-03-01

Obesity has been implicated in the development of many cancers. This can lead to genome damage, especially in the form of double-strand break, the presence of which is now easily detected through nuclear phosphorylation of histone H2AX (γ-H2AX) focus assay. Recently, the endothelin (ET) axis has also been shown to have a role in the growth and progression of several tumors, including lung cancer. The aim of this study was to evaluate the ET-1 system transcriptional alterations and γ-H2AX in lung tissue of Zucker rats subdivided into obese (O, n=22) and controls (CO, n=18) rats: under either fasting conditions (CO(fc)-O(fc)) or acute hyperglycemia (CO(AH)-O(AH)). Significantly higher prepro-ET-1 (p=0.05) and ET-converting enzyme (ECE)-2 mRNA expression was observed in O with respect to CO. A significant positive association was observed between prepro-ET-1 and ET-A in the whole rat population (p=0.009) or in the obese group alone (p=0.007). The levels of γ-H2AX in O and in O(AH) rats were significantly higher (p=0.019) than in the corresponding CO and CO(AH) rats (p=0.038). The study shows an inappropriate secretion of ET-1 in O animals with a parallel DNA damage in their lungs, providing novel mechanisms by which ET receptor antagonist may exert organ protection.

Bardoxolone methyl analogs RTA 405 and dh404 are well tolerated and exhibit efficacy in rodent models of Type 2 diabetes and obesity.

PubMed

Chin, Melanie; Lee, Chun-Yue Ivy; Chuang, Jen-Chieh; Bumeister, Ron; Wigley, W Christian; Sonis, Stephen T; Ward, Keith W; Meyer, Colin

2013-06-15

Bardoxolone methyl and related triterpenoids are well tolerated and efficacious in numerous animal models potentially relevant to patients with Type 2 diabetes and chronic kidney disease. These agents enhance glucose control and regulate lipid accumulation in rodent models of diabetes and obesity, and improve renal function, reduce inflammation, and prevent structural injury in models of renal disease. However, a recent study in Zucker diabetic fatty (ZDF) rats noted poor tolerability with the bardoxolone methyl analog RTA 405 within 1 mo after treatment initiation, although this study was confounded in part by the use of an impure RTA 405 batch. To investigate these discordant observations, the present studies were conducted to further characterize triterpenoids in rodent models of diabetes and obesity. A follow-up study was conducted in ZDF rats with two related triterpenoids (RTA 405 and dh404) for 1.5 mo. Consistent with previous rodent experience, and in contrast to the more recent ZDF report, ZDF rats administered RTA 405 or dh404 exhibited no adverse clinical signs, had laboratory values similar to controls, and exhibited no evidence of adverse liver or kidney histopathology. Additionally, RTA 405 was well tolerated in streptozotocin-induced Type 1 diabetic rats and high-fat-diet-induced obese mice. The present results are consistent with the overall published body of data obtained with triterpenoids and provide further evidence that these molecules are well tolerated without adverse effects on hepatobiliary or renal function in rodent models of diabetes and obesity.

Evidence of glycemia-lowering effect by a Cynara scolymus L. extract in normal and obese rats.

PubMed

Fantini, Noemi; Colombo, Giancarlo; Giori, Andrea; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Carai, Mauro A M

2011-03-01

Several recent preliminary clinical studies have suggested that artichoke (Cynara scolymus L., Asteraceae family) preparations may be capable of lowering post-prandial glycemia. The present study was designed to test this hypothesis in laboratory rats. To this aim, non-selected Wistar and genetically obese Zucker rats were treated acutely with a purified extract of Cynara scolymus flowering heads (500-1500 mg/kg by gavage) immediately prior to 1 h access to a fixed amount of food. Glycemia was recorded 60, 120 and 360 min after food presentation. Treatment with Cynara scolymus flowering head extract resulted in a significant decrease of post-prandial glycemia in both rat strains. The lack of any fiber content in this Cynara scolymus flowering head extract excludes the involvement of dietary fibers in glycemia reduction. The results obtained constitute the first evidence of a hypoglycemic effect of an artichoke preparation in laboratory rodents and confirm previous observations made in humans. Copyright © 2010 John Wiley & Sons, Ltd.

Hyaluronan 35kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo.

PubMed

Kim, Yeojung; Kessler, Sean P; Obery, Dana R; Homer, Craig R; McDonald, Christine; de la Motte, Carol A

2017-10-01

Maintaining a healthy intestinal barrier, the primary physical barrier between intestinal microbiota and the underlying lamina propria, is critical for optimal health. Epithelial integrity is essential for the prevention of the entrance of luminal contents, such as bacteria and their products, through the large intestinal barrier. In this study, we investigated the protective functions of biosynthetic, specific sized, hyaluronan around 35kDa (HA35) on intestinal epithelium in healthy mice, as well as mice infected Citrobacter rodentium, an established model that mimics infection with a serious human pathogen, enteropathogenic E. coli (EPEC). Our results reveal that treatment with HA35 protects mice from Citrobacter infection and enhances the epithelial barrier function. In particular, we have found that HA35 induces the expression of tight junction protein zonula occludens (ZO)-1 in both healthy and Citrobacter infected mice, as demonstrated by immunoflurorescence and Western blot analyses. Furthermore, we determined that HA35 treatment enhances ZO-1 expression and reduces intestinal permeability at the early stages of dextran sulfate sodium (DSS)-induced colitis in mice. Together, our data demonstrate that the expression and functionality of tight junctions, are increased by HA35 treatment, suggesting a novel mechanism for the protection from Citrobacter infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic Relatedness of WNIN and WNIN/Ob with Major Rat Strains in Biomedical Research.

PubMed

Battula, Kiran Kumar; Nappanveettil, Giridharan; Nakanishi, Satoshi; Kuramoto, Takashi; Friedman, Jeffry M; Kalashikam, Rajender Rao

2015-06-01

WNIN (Wistar/NIN) is an inbred rat strain maintained at National Institute of Nutrition (NIN) for more than 90 years, and WNIN/Ob is an obese mutant originated from it. To determine their genetic relatedness with major rat strains in biomedical research, they were genotyped at various marker loci. The recently identified markers for albino and hooded mutations which clustered all the known albino rats into a single lineage also included WNIN and WNIN/Ob rats. Genotyping using microsatellite DNA markers and phylogenetic analysis with 49 different rat strains suggested that WNIN shares a common ancestor with many Wistar originated strains. Fst estimates and Fischer's exact test suggest that WNIN rats differed significantly from all other strains tested. WNIN/Ob though shows hyper-leptinemia, like Zucker fatty rat, did not share the Zucker fatty rat mutation. The above analyses suggest WNIN as a highly differentiated rat strain and WNIN/Ob a novel obese mutant evolved from it.

Supplemental fructose attenuates postprandial glycemia in Zucker fatty fa/fa rats.

PubMed

Wolf, Bryan W; Humphrey, Phillip M; Hadley, Craig W; Maharry, Kati S; Garleb, Keith A; Firkins, Jeffrey L

2002-06-01

Experiments were conducted to evaluate the effects of supplemental fructose on postprandial glycemia. After overnight food deprivation, Zucker fatty fa/fa rats were given a meal glucose tolerance test. Plasma glucose response was determined for 180 min postprandially. At a dose of 0.16 g/kg body, fructose reduced (P < 0.05) the incremental area under the curve (AUC) by 34% when supplemented to a glucose challenge and by 32% when supplemented to a maltodextrin (a rapidly digested starch) challenge. Similarly, sucrose reduced (P = 0.0575) the incremental AUC for plasma glucose when rats were challenged with maltodextrin. Second-meal glycemic response was not affected by fructose supplementation to the first meal, and fructose supplementation to the second meal reduced (P < 0.05) postprandial glycemia when fructose had been supplemented to the first meal. In a dose-response study (0.1, 0.2, and 0.5 g/kg body), supplemental fructose reduced (P < 0.01) the peak rise in plasma glucose (linear and quadratic effects). In the final experiment, a low dose of fructose (0.075 g/kg body) reduced (P < 0.05) the incremental AUC by 18%. These data support the hypothesis that small amounts of oral fructose or sucrose may be useful in lowering the postprandial blood glucose response.

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome.

PubMed

van Dijk, Christian G M; Oosterhuis, Nynke R; Xu, Yan Juan; Brandt, Maarten; Paulus, Walter J; van Heerebeek, Loek; Duncker, Dirk J; Verhaar, Marianne C; Fontoura, Dulce; Lourenço, André P; Leite-Moreira, Adelino F; Falcão-Pires, Inês; Joles, Jaap A; Cheng, Caroline

2016-04-01

The combination of cardiac and renal disease driven by metabolic risk factors, referred to as cardiorenal metabolic syndrome (CRMS), is increasingly recognized as a critical pathological entity. The contribution of (micro)vascular injury to CRMS is considered to be substantial. However, mechanistic studies are hampered by lack of in vivo models that mimic the natural onset of the disease. Here, we evaluated the coronary and renal microvasculature during CRMS development in obese diabetic Zucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. Echocardiographic, urine, and blood evaluations were conducted in 3 groups (Wistar-Kyoto, lean ZSF1, and obese ZSF1) at 20 and 25 weeks of age. Immunohistological evaluation of renal and cardiac tissues was conducted at both time points. At 20 and 25 weeks, obese ZSF1 rats showed higher body weight, significant left ventricular hypertrophy, and impaired diastolic function compared with all other groups. Indices of systolic function did not differ between groups. Obese ZSF1 rats developed hyperproliferative vascular foci in the subendocardium, which lacked microvascular organization and were predilection sites of inflammation and fibrosis. In the kidney, obese ZSF1 animals showed regression of the peritubular and glomerular microvasculature, accompanied by tubulointerstitial damage, glomerulosclerosis, and proteinuria. The obese ZSF1 rat strain is a suitable in vivo model for CRMS, sharing characteristics with the human syndrome during the earliest onset of disease. In these rats, CRMS induces microvascular fibrotic responses in heart and kidneys, associated with functional impairment of both organs. © 2016 American Heart Association, Inc.

Nebivolol ameliorated kidney damage in Zucker diabetic fatty rats by regulation of oxidative stress/NO pathway: comparison with captopril.

PubMed

Wang, Yan; An, Wenjing; Zhang, Fei; Niu, Mengzhen; Liu, Yu; Shi, Ruizan

2018-06-23

The aim was to evaluate the effects and mechanisms of nebivolol on renal damage in Zucker diabetic fatty (ZDF) rats, in comparison with those of atenolol and captopril. Animals were divided into: control lean Zucker rats, ZDF rats, ZDF rats orally treated with nebivolol (10 mg/kg), atenolol (100 mg/kg) or captopril (40 mg/kg) for 6 months. Systolic blood pressure (SBP), blood glucose, kidney structure and function, plasma and kidney levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA), and oxidant status were evaluated. Kidney expressions of AMP-activated protein kinase (AMPK), NADPH oxidase (NOX) isoforms 2 and 4 and subunit p22 phox , nitric oxide synthase (NOS) isoforms, eNOS uncoupling, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 were tested. All drugs induced a similar control of SBP. Nebivolol did not affect the increased plasma glucose. Unlike atenolol, nebivolol prevented the decrease in plasma insulin, and, like captopril, it reduced plasma lipid contents. Nebivolol ameliorated, to a greater extent than captopril, damages to renal structure and function, which were associated with an improvement in interlobular artery dysfunction. Nebivolol elevated kidney phosphorylation of AMPK, attenuated NOX4 and p22 phox expression and oxidative stress marker levels. Nebivolol increased plasma and renal NO, enhanced expressions of eNOS, p-eNOS and nNOS, and suppressed eNOS uncoupling and iNOS expression. High ADMA in plasma and kidney were decreased by nebivolol through increasing DDAH2 and decreasing PRMT1. Long-term treatment of nebivolol ameliorated diabetic nephropathy, at least in part, via regulation of renal oxidative stress/NO pathway. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effect of combination treatment of S–amlodipine with peroxisome proliferator-activated receptor agonists on metabolic and cardiovascular parameters in Zucker fa/fa rats

PubMed Central

2014-01-01

Background Type 2 diabetes is a complex metabolic disorder characterized by hyperglycemia, impaired glucose tolerance and insulin resistance associated with dyslipidemia and hypertension. The available drugs are not sufficiently efficacious in reducing cardiovascular risk and restoring normal glucose metabolism associated with type 2 diabetes as a mono- or a combination therapy. The present study examined the combined effects of an antihypertensive (S-Amlodipine) and an insulin-sensitizing agent, peroxisome proliferator-activated receptor (PPAR) agonists (Pioglitazone and Ragaglitazar), on cardiovascular risk factors in aged diabetic and insulin-resistant Zucker fa/fa rats. Methods Following combination treatment for 14 days, blood pressure (BP), serum glucose, total cholesterol and triglycerides were measured. Aortic ring study was conducted to determine the effect of combination treatments on phenylephrine-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation. Results In combination, S-Amlodipine and Pioglitazone significantly reduced blood glucose (115.1 ± 6.6 vs. 81.7 ± 4.2), BP (184.4 ± 5.0 vs. 155.1 ± 5.0), serum triglycerides (362.5 ± 47.5 vs. 211.1 ± 23.7) and glucose intolerance when compared with vehicle treated Zucker fa/fa rats. Similar results were observed with the combination of S-Amlodipine and Ragaglitazar (Triglycerides, 362.5 ± 47.5 vs. 252.34 ± 27.86; BP, 184.4 ± 5.0 vs. 159.0 ± 8.0) except for serum glucose. ACh-induced vasorelaxation in aortic rings was also superior with both of the combinations compared to individual treatment. Furthermore, there was less body weight gain and food intake with S-Amlodipine and Pioglitazone combination in Zucker fa/fa rats. S-Amlodipine itself caused significant reduction in glucose (115.1 ± 6.6 vs. 89.7 ± 2.7) and BP (184.4 ± 5.0 vs. 156.1 ± 4.0) with improvement in insulin sensitivity observed through oral glucose

Dual implantation of a radio-telemeter and vascular access port allows repeated hemodynamic and pharmacological measures in conscious lean and obese rats.

PubMed

Bussey, C T; Leeuw, A E de; Cook, R F; Ashley, Z; Schofield, J; Lamberts, R R

2014-07-01

Expansion of physiological knowledge increasingly requires examination of processes in the normal, conscious state. The current study describes a novel approach combining surgical implantation of radio-telemeters with vascular access ports (VAPs) to allow repeated hemodynamic and pharmacological measures in conscious rats. Dual implantation was conducted on 16-week-old male lean and obese Zucker rats. Continued viability one month after surgery was observed in 67% of lean and 44% of obese animals, giving an overall 54% completion rate. Over the five-week measurement period, reliable and reproducible basal mean arterial pressure and heart rate measures were observed. VAP patency and receptor-independent vascular reactivity were confirmed by consistent hemodynamic responses to sodium nitroprusside (6.25 µg/kg). Acutely, minimal hemodynamic responses to repeated bolus administration of 0.2 mL saline indicated no significant effect of increased blood volume or administration stress, making repeated acute measures viable. Similarly, repeated administration of the β-adrenoceptor agonist dobutamine (30 µg/kg) at 10 min intervals resulted in reproducible hemodynamic changes in both lean and obese animals. Therefore, our study demonstrates that this new approach is viable for the acute and chronic assessment of hemodynamic and pharmacological responses in both lean and obese conscious rats. This technique reduces the demand for animal numbers and allows hemodynamic measures with minimal disruption to animals' welfare, while providing reliable and reproducible results over several weeks. In conclusion, dual implantation of a radio-telemeter and VAP introduces a valuable technique for undertaking comprehensive studies involving repeated pharmacological tests in conscious animals to address important physiological questions. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Effects of baked and raw salmon fillet on lipids and n-3 PUFAs in serum and tissues in Zucker fa/fa rats​​​​​​​​​​​​​​​​​​​​.

PubMed

Vikøren, Linn A; Drotningsvik, Aslaug; Bergseth, Marthe T; Mjøs, Svein A; Mola, Nazanin; Leh, Sabine; Mellgren, Gunnar; Gudbrandsen, Oddrun A

2017-01-01

Knowledge of the health impact of consuming heat-treated versus raw fish fillet is limited. To investigate effects of baked or raw salmon fillet intake on lipids and n-3 PUFAs in serum and tissues, obese Zucker fa/fa rats were fed diets containing 25% of protein from baked or raw salmon fillet and 75% of protein from casein, or casein as the sole protein source (control group) for four weeks. Salmon diets had similar composition of amino and fatty acids. Growth and energy intake were similar in all groups. Amounts of lipids and n-3 PUFAs in serum, liver and skeletal muscle were similar between rats fed baked or raw salmon fillet. When compared to the control group, rats fed baked salmon had lower serum total and LDL cholesterol and higher serum triacylglycerol levels. Both raw and baked salmon groups had lower HDL cholesterol level when compared to control rats. In conclusion, baking as a preparation method does not alter protein and fat qualities of salmon fillets, and intake of baked and raw salmon fillets gave similar effects on lipids and n-3 PUFAs in serum and tissues from rats.

Effects of baked and raw salmon fillet on lipids and n-3 PUFAs in serum and tissues in Zucker fa/fa rats​​​​​​​​​​​​​​​​​​​​

PubMed Central

Vikøren, Linn A.; Drotningsvik, Aslaug; Bergseth, Marthe T.; Mjøs, Svein A.; Mola, Nazanin; Leh, Sabine; Mellgren, Gunnar; Gudbrandsen, Oddrun A.

2017-01-01

ABSTRACT Knowledge of the health impact of consuming heat-treated versus raw fish fillet is limited. To investigate effects of baked or raw salmon fillet intake on lipids and n-3 PUFAs in serum and tissues, obese Zucker fa/fa rats were fed diets containing 25% of protein from baked or raw salmon fillet and 75% of protein from casein, or casein as the sole protein source (control group) for four weeks. Salmon diets had similar composition of amino and fatty acids. Growth and energy intake were similar in all groups. Amounts of lipids and n-3 PUFAs in serum, liver and skeletal muscle were similar between rats fed baked or raw salmon fillet. When compared to the control group, rats fed baked salmon had lower serum total and LDL cholesterol and higher serum triacylglycerol levels. Both raw and baked salmon groups had lower HDL cholesterol level when compared to control rats. In conclusion, baking as a preparation method does not alter protein and fat qualities of salmon fillets, and intake of baked and raw salmon fillets gave similar effects on lipids and n-3 PUFAs in serum and tissues from rats. PMID:28659746

Effects of estradiol, estrogen receptor subtype-selective agonists and genistein on glucose metabolism in leptin resistant female Zucker diabetic fatty (ZDF) rats.

PubMed

Weigt, Carmen; Hertrampf, Torsten; Flenker, Ulrich; Hülsemann, Frank; Kurnaz, Pinar; Fritzemeier, Karl Heinrich; Diel, Patrick

2015-11-01

The leptin resistant Zucker diabetic fatty (ZDF) rats are hyperphagic and become obese, but whereas the males develop type 2 diabetes mellitus (T2DM), the females remain euglycaemic. As estrogen deficiency is known to increase the risk of developing T2DM, we evaluated the role of ER subtypes alpha and beta in the development of glucose tolerance in leptin resistant ovariectomized (OVX) ZDF rats. At least six rats per group were treated with either vehicle (OVX), 17β-estradiol (E2), ER subtype-selective agonists (Alpha and Beta), or genistein (Gen) for 17 weeks. At the end of the treatment period a glucose tolerance assay was performed and the metabolic flux of (13)C-glucose for the E2 group was investigated. OVX ZDF rats treated with E2, Alpha, Beta, and Gen tolerated the glucose significantly better than untreated controls. E2 treatment increased absorbance/flux of (13)C-glucose to metabolic relevant tissues such liver, adipose tissue, gastrocnemius, and soleus muscle. Moreover, whereas Alpha treatment markedly increased mRNA expression of GLUT4 in gastrocnemius muscle, Beta treatment resulted in the largest fiber sizes of the soleus muscle. Treatment with Gen increased both the mRNA expression of GLUT 4 and the fiber sizes in the skeletal muscle. In addition, E2 and Alpha treatment decreased food intake and body weight gain. In summary, estrogen-improved glucose absorption is mediated via different molecular mechanisms: while activation of ER alpha seems to stimulate muscular GLUT4 functionality, activation of ER beta results in a hypertrophy of muscle fibers. In addition, selective activation of ER alpha decreased food intake and body weight gain. Our data further indicate that ER subtype-selective agonists and genistein improve systemic glucose tolerance also in the absence of a functional leptin signaling pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diet-Induced Obesity in Male C57BL/6 Mice Decreases Fertility as a Consequence of Disrupted Blood-Testis Barrier

PubMed Central

Fan, Yong; Liu, Yue; Xue, Ke; Gu, Guobao; Fan, Weimin; Xu, Yali; Ding, Zhide

2015-01-01

Obesity is a complex metabolic disease that is a serious detriment to both children and adult health, which induces a variety of diseases, such as cardiovascular disease, type II diabetes, hypertension and cancer. Although adverse effects of obesity on female reproduction or oocyte development have been well recognized, its harmfulness to male fertility is still unclear because of reported conflicting results. The aim of this study was to determine whether diet-induced obesity impairs male fertility and furthermore to uncover its underlying mechanisms. Thus, male C57BL/6 mice fed a high-fat diet (HFD) for 10 weeks served as a model of diet-induced obesity. The results clearly show that the percentage of sperm motility and progressive motility significantly decreased, whereas the proportion of teratozoospermia dramatically increased in HFD mice compared to those in normal diet fed controls. Besides, the sperm acrosome reaction fell accompanied by a decline in testosterone level and an increase in estradiol level in the HFD group. This alteration of sperm function parameters strongly indicated that the fertility of HFD mice was indeed impaired, which was also validated by a low pregnancy rate in their mated normal female. Moreover, testicular morphological analyses revealed that seminiferous epithelia were severely atrophic, and cell adhesions between spermatogenic cells and Sertoli cells were loosely arranged in HFD mice. Meanwhile, the integrity of the blood-testis barrier was severely interrupted consistent with declines in the tight junction related proteins, occludin, ZO-1 and androgen receptor, but instead endocytic vesicle-associated protein, clathrin rose. Taken together, obesity can impair male fertility through declines in the sperm function parameters, sex hormone level, whereas during spermatogenesis damage to the blood-testis barrier (BTB) integrity may be one of the crucial underlying factors accounting for this change. PMID:25886196

Diet-induced obesity in male C57BL/6 mice decreases fertility as a consequence of disrupted blood-testis barrier.

PubMed

Fan, Yong; Liu, Yue; Xue, Ke; Gu, Guobao; Fan, Weimin; Xu, Yali; Ding, Zhide

2015-01-01

Obesity is a complex metabolic disease that is a serious detriment to both children and adult health, which induces a variety of diseases, such as cardiovascular disease, type II diabetes, hypertension and cancer. Although adverse effects of obesity on female reproduction or oocyte development have been well recognized, its harmfulness to male fertility is still unclear because of reported conflicting results. The aim of this study was to determine whether diet-induced obesity impairs male fertility and furthermore to uncover its underlying mechanisms. Thus, male C57BL/6 mice fed a high-fat diet (HFD) for 10 weeks served as a model of diet-induced obesity. The results clearly show that the percentage of sperm motility and progressive motility significantly decreased, whereas the proportion of teratozoospermia dramatically increased in HFD mice compared to those in normal diet fed controls. Besides, the sperm acrosome reaction fell accompanied by a decline in testosterone level and an increase in estradiol level in the HFD group. This alteration of sperm function parameters strongly indicated that the fertility of HFD mice was indeed impaired, which was also validated by a low pregnancy rate in their mated normal female. Moreover, testicular morphological analyses revealed that seminiferous epithelia were severely atrophic, and cell adhesions between spermatogenic cells and Sertoli cells were loosely arranged in HFD mice. Meanwhile, the integrity of the blood-testis barrier was severely interrupted consistent with declines in the tight junction related proteins, occludin, ZO-1 and androgen receptor, but instead endocytic vesicle-associated protein, clathrin rose. Taken together, obesity can impair male fertility through declines in the sperm function parameters, sex hormone level, whereas during spermatogenesis damage to the blood-testis barrier (BTB) integrity may be one of the crucial underlying factors accounting for this change.

Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction.

PubMed

Knudson, Jarrod D; Dincer, U Deniz; Zhang, Cuihua; Swafford, Albert N; Koshida, Ryoji; Picchi, Andrea; Focardi, Marta; Dick, Gregory M; Tune, Johnathan D

2005-07-01

Obesity is associated with marked increases in plasma leptin concentration, and hyperleptinemia is an independent risk factor for coronary artery disease. As a result, the purpose of this investigation was to test the following hypotheses: 1) leptin receptors are expressed in coronary endothelial cells; and 2) hyperleptinemia induces coronary endothelial dysfunction. RT-PCR analysis revealed that the leptin receptor gene is expressed in canine coronary arteries and human coronary endothelium. Furthermore, immunocytochemistry demonstrated that the long-form leptin receptor protein (ObRb) is present in human coronary endothelium. The functional effects of leptin were determined using pressurized coronary arterioles (<130 microm) isolated from Wistar rats, Zucker rats, and mongrel dogs. Leptin induced pharmacological vasodilation that was abolished by denudation and the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester and was absent in obese Zucker rats. Intracoronary leptin dose-response experiments were conducted in anesthetized dogs. Normal and obese concentrations of leptin (0.1-3.0 microg/min ic) did not significantly change coronary blood flow or myocardial oxygen consumption; however, obese concentrations of leptin significantly attenuated the dilation to graded intracoronary doses of acetylcholine (0.3-30.0 microg/min). Additional experiments were performed in canine coronary rings, and relaxation to acetylcholine (6.25 nmol/l-6.25 micromol/l) was significantly attenuated by obese concentrations of leptin (625 pmol/l) but not by physiological concentrations of leptin (250 pmol/l). The major findings of this investigation were as follows: 1) the ObRb is present in coronary arteries and coupled to pharmacological, nitric oxide-dependent vasodilation; and 2) hyperleptinemia produces significant coronary endothelial dysfunction.

ZiBuPiYin recipe improves cognitive decline by regulating gut microbiota in Zucker diabetic fatty rats

PubMed Central

Wang, Wang; Xiang, Hong; Xu, Huiying; Liang, Lina; Sui, Hua; Zhan, Libin; Lu, Xiaoguang

2017-01-01

Numerous researches supported that microbiota can influence behavior and modulate cognitive function through “microbiota-gut-brain” axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD. PMID:28099913

ZiBuPiYin recipe improves cognitive decline by regulating gut microbiota in Zucker diabetic fatty rats.

PubMed

Gu, Chunyan; Zhou, Wen; Wang, Wang; Xiang, Hong; Xu, Huiying; Liang, Lina; Sui, Hua; Zhan, Libin; Lu, Xiaoguang

2017-04-25

Numerous researches supported that microbiota can influence behavior and modulate cognitive function through "microbiota-gut-brain" axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD.

Probiotics modify tight-junction proteins in an animal model of nonalcoholic fatty liver disease

PubMed Central

Briskey, David; Heritage, Mandy; Jaskowski, Lesley-Anne; Peake, Jonathan; Gobe, Glenda; Subramaniam, V. Nathan; Crawford, Darrell; Campbell, Catherine; Vitetta, Luis

2016-01-01

Background: We have investigated the effects of a multispecies probiotic preparation containing a combination of probiotic bacterial genera that included Bifidobacteria, Lactobacilli and a Streptococcus in a mouse model of high-fat diet or obesity-induced liver steatosis. Methods: Three groups of C57B1/6J mice were fed either a standard chow or a high-fat diet for 20 weeks, while a third group was fed a high-fat diet for 10 weeks and then concomitantly administered probiotics for a further 10 weeks. Serum, liver and large bowel samples were collected for analysis. Results: The expression of the tight-junction proteins ZO-1 and ZO-2 was reduced (p < 0.05) in high-fat diet-fed mice compared to chow-fed mice. Probiotic supplementation helped to maintain tight ZO-1 and ZO-2 expression compared with the high-fat diet group (p < 0.05), but did not restore ZO-1 or ZO-2 expression compared with chow-fed mice. Mice fed a high-fat diet ± probiotics had significant steatosis development compared with chow-fed mice (p < 0.05); steatosis was less severe in the probiotics group compared with the high-fat diet group. Hepatic triglyceride concentration was higher in mice fed a high-fat diet ± probiotics compared with the chow group (p < 0.05), and was lower in the probiotics group compared with the high-fat diet group (p < 0.05). Compared with chow-fed mice, serum glucose, cholesterol concentration and the activity of alanine transaminase were higher (p < 0.05), whereas serum triglyceride concentration was lower (p < 0.05) in mice fed a high-fat diet ± probiotics. Conclusions: Supplementation with a multispecies probiotic formulation helped to maintain tight-junction proteins ZO-1 and ZO-2, and reduced hepatic triglyceride concentration compared with a high-fat diet alone. PMID:27366215

Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability.

PubMed

Cani, P D; Possemiers, S; Van de Wiele, T; Guiot, Y; Everard, A; Rottier, O; Geurts, L; Naslain, D; Neyrinck, A; Lambert, D M; Muccioli, G G; Delzenne, N M

2009-08-01

Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions

The Loyalty—New Hebrides Arc collision: Effects on the Loyalty Ridge and basin system, Southwest Pacific (first results of the ZoNéCo programme)

NASA Astrophysics Data System (ADS)

Lafoy, Yves; Missegue, Francois; Cluzel, Dominique; Le Suave, Raymond

1996-06-01

The ZoNéCo 1 and 2 cruises of Ifremer's Research Vessel L'Atalante, collected new swath bathymetry and geophysical data over the southern and northern segments of the basins and ridges forming the Loyalty system. Between the two surveyed areas, previous studies found evidence for the resistance of the Loyalty Ridge to subduction beneath the New Hebrides trench near 22°S 169°E. On the subducted plate, except for seismicity related to the downbending of the Australian plate, recorded shallow seismicity is sparse within the Loyalty system (Ridge and Basin) where reliable focal mechanism solutions are almost absent. Swath bathymetry, seismic reflection and magnetic data acquired during the ZoNéCo 1 and 2 cruises revealed a transverse asymmetric morphology in the Loyalty system, and an along-strike horst and graben structure on the discontinuous Loyalty Ridge. South of 23°50'S and at 20°S, the two WSW-ENE-trending fault systems, respectively, sinistral and dextral, that crosscut the southern and northern segments of the Loyalty system, are interpreted as due to the early effects of collision with the New Hebrides Arc. A NNW-SSE trend, evident along the whole Loyalty system and on the island of New Caledonia, is interpreted as an inherited structural trend that may have been reactivated through flexure of the Australian lithospheric plate at the subduction zone. Overall then, the morphology, structure and evolution of the southern and northern segments of the Loyalty system probably result from the combined effects of the Australian plate lithospheric bulge, the active Loyalty-New Hebrides collision and the overthrust of the New Caledonian ophiolite.

Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat.

PubMed

Goldsmith, Felicia; Guice, Justin; Page, Ryan; Welsh, David A; Taylor, Christopher M; Blanchard, Eugene E; Luo, Meng; Raggio, Anne M; Stout, Rhett W; Carvajal-Aldaz, Diana; Gaither, Amanda; Pelkman, Christine; Ye, Jianping; Martin, Roy J; Geaghan, James; Durham, Holiday A; Coulon, Diana; Keenan, Michael J

2017-01-01

To determine if whole-grain (WG) flour with resistant starch (RS) will produce greater fermentation than isolated RS in obese Zucker Diabetic Fatty (ZDF) rats, and whether greater fermentation results in different microbiota, reduced abdominal fat, and increased insulin sensitivity. This study utilized four groups fed diets made with either isolated digestible control starch, WG control flour (6.9% RS), isolated RS-rich corn starch (25% RS), or WG corn flour (25% RS). ZDF rats fermented RS and RS-rich WG flour to greatest extent among groups. High-RS groups had increased serum glucagon-like peptide 1 (GLP-1) active. Feeding isolated RS showed greater Bacteroidetes to Firmicutes phyla among groups, and rats consuming low RS diets possessed more bacteria in Lactobacillus genus. However, no differences in abdominal fat were observed, but rats with isolated RS had greatest insulin sensitivity among groups. Data demonstrated ZDF rats (i) possess a microbiota that fermented RS, and (ii) WG high-RS fermented better than purified RS. However, fermentation and microbiota changes did not translate into reduced abdominal fat. The defective leptin receptor may limit ZDF rats from responding to increased GLP-1 and different microbiota for reducing abdominal fat, but did not prevent improved insulin sensitivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats.

PubMed

Szokol, Miklos; Priksz, Daniel; Bombicz, Mariann; Varga, Balazs; Kovacs, Arpad; Fulop, Gabor Aron; Csipo, Tamas; Posa, Aniko; Toth, Attila; Papp, Zoltan; Szilvassy, Zoltan; Juhasz, Bela

2017-10-12

The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF), fractional shortening (FS), isovolumetric relaxation time (IVRT), mitral annular plane systolic excursion (MAPSE), and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status.

Thyroid hormone modulates food intake and glycemia via ghrelin secretion in Zucker fatty rats.

PubMed

Patel, K; Joharapurkar, A; Dhanesha, N; Patel, V; Kshirsagar, S; Raval, P; Raval, S; Jain, M R

2014-10-01

Hyperthyroidism is known to increase food intake and central administration of thyroid hormone shows acute orexigenic effects in rodents. We investigated whether T3 influences appetite and glucose homeostasis by modulating circulating ghrelin, an important orexigenic hormone, in Zucker fatty rats. The acute anorectic effects of T3 and ghrelin mimetic MK-0677 were studied in rats trained for fasting induced food intake. The serum concentration of T3, ghrelin, glucose, triglycerides, and liver glycogen were estimated. The involvement of sympathetic nervous system was evaluated by conducting similar experiments in vagotomized rats. T3 increased food intake and glucose in rats over 4 h, with increase in serum T3 and decrease in liver glycogen. T3 treatment was associated with increase in serum ghrelin. An additive effect on appetite and glucose was observed when T3 (oral) was administered with central (intracerebroventricular) administration of a ghrelin mimetic, MK-0677. Ghrelin antagonist, compound 8a, antagonized the hyperglycemic and hyperphagic effects of T3. In vagotomized rats, T3 did not show increase in appetite as well as glucose. Serum ghrelin levels were unchanged in these animals after T3 treatment. However, T3 showed increase in serum triglyceride levels indicating its peripheral lipolytic effect, in vagotomized as well as sham treated animals. To conclude, acute orexigenic and hyperglycemic effects of T3 are associated with ghrelin secretion and activity. This effect seems to be mediated via vagus nerves, and is independent of glucoregulatory hormones. © Georg Thieme Verlag KG Stuttgart · New York.

Sustained Exendin-4 Secretion through Gene Therapy Targeting Salivary Glands in Two Different Rodent Models of Obesity/Type 2 Diabetes

PubMed Central

Raimondi, Laura; Pagano, Claudio; Egan, Josephine M.; Cozzi, Andrea; Cinci, Lorenzo; Loreto, Andrea; Manni, Maria E.; Berretti, Silvia; Morelli, Annamaria; Zheng, Changyu; Michael, Drew G.; Maggi, Mario; Vettor, Roberto; Chiorini, John A.; Mannucci, Edoardo; Rotella, Carlo M.

2012-01-01

Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9±42.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2±72 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile. PMID:22808093

P-glycoprotein regulates blood–testis barrier dynamics via its effects on the occludin/zonula occludens 1 (ZO-1) protein complex mediated by focal adhesion kinase (FAK)

PubMed Central

Su, Linlin; Mruk, Dolores D.; Lui, Wing-Yee; Lee, Will M.; Cheng, C. Yan

2011-01-01

The blood–testis barrier (BTB), one of the tightest blood–tissue barriers in the mammalian body, creates an immune-privileged site for postmeiotic spermatid development to avoid the production of antibodies against spermatid-specific antigens, many of which express transiently during spermiogenesis and spermiation. However, the BTB undergoes extensive restructuring at stage VIII of the epithelial cycle to facilitate the transit of preleptotene spermatocytes and to prepare for meiosis. This action thus prompted us to investigate whether this stage can be a physiological window for the delivery of therapeutic and/or contraceptive drugs across the BTB to exert their effects at the immune-privileged site. Herein, we report findings that P-glycoprotein, an ATP-dependent efflux drug transporter and an integrated component of the occludin/zonula occludens 1 (ZO-1) adhesion complex at the BTB, structurally interacted with focal adhesion kinase (FAK), creating the occludin/ZO-1/FAK/P-glycoprotein regulatory complex. Interestingly, a knockdown of P-glycoprotein by RNAi was found to impede Sertoli cell BTB function, making the tight junction (TJ) barrier “leaky.” This effect was mediated by changes in the protein phosphorylation status of occludin via the action of FAK, thereby affecting the endocytic vesicle-mediated protein trafficking events that destabilized the TJ barrier. However, the silencing of P-glycoprotein, although capable of impeding drug transport across the BTB and TJ permeability barrier function, was not able to induce the BTB to be “freely” permeable to adjudin. These findings indicate that P-glycoprotein is involved in BTB restructuring during spermatogenesis but that P-glycoprotein–mediated restructuring does not “open up” the BTB to make it freely permeable to drugs. PMID:22106313

Obesity and severe obesity forecasts through 2030.

PubMed

Finkelstein, Eric A; Khavjou, Olga A; Thompson, Hope; Trogdon, Justin G; Pan, Liping; Sherry, Bettylou; Dietz, William

2012-06-01

Previous efforts to forecast future trends in obesity applied linear forecasts assuming that the rise in obesity would continue unabated. However, evidence suggests that obesity prevalence may be leveling off. This study presents estimates of adult obesity and severe obesity prevalence through 2030 based on nonlinear regression models. The forecasted results are then used to simulate the savings that could be achieved through modestly successful obesity prevention efforts. The study was conducted in 2009-2010 and used data from the 1990 through 2008 Behavioral Risk Factor Surveillance System (BRFSS). The analysis sample included nonpregnant adults aged ≥ 18 years. The individual-level BRFSS variables were supplemented with state-level variables from the U.S. Bureau of Labor Statistics, the American Chamber of Commerce Research Association, and the Census of Retail Trade. Future obesity and severe obesity prevalence were estimated through regression modeling by projecting trends in explanatory variables expected to influence obesity prevalence. Linear time trend forecasts suggest that by 2030, 51% of the population will be obese. The model estimates a much lower obesity prevalence of 42% and severe obesity prevalence of 11%. If obesity were to remain at 2010 levels, the combined savings in medical expenditures over the next 2 decades would be $549.5 billion. The study estimates a 33% increase in obesity prevalence and a 130% increase in severe obesity prevalence over the next 2 decades. If these forecasts prove accurate, this will further hinder efforts for healthcare cost containment. Copyright © 2012 Elsevier Inc. All rights reserved.

Potential utility of combination therapy with nateglinide and telmisartan for metabolic derangements in Zucker Fatty rats.

PubMed

Kajioka, T; Miura, K; Kitahara, Y; Yamagishi, S

2007-12-01

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular disease. Insulin resistance and/or impaired early-phase insulin secretion are major determinants of postprandial hyperglycemia. In this study, we investigated the potential utility of combination therapy with telmisartan, an angiotensin II receptor blocker and nateglinide, a rapid-onset/short-duration insulinotropic agent, for the treatment of postprandial hyperglycemia and metabolic derangements in Zucker Fatty (ZF) rats. ZF rats fed twice daily were given vehicle, 50 mg/kg of nateglinide, 5 mg/kg of telmisartan, or both for 6 weeks. Combination therapy with nateglinide and telmisartan for 2 weeks ameliorated postprandial hyperglycemia in ZF rats fed twice daily. Furthermore, 6-week treatment with nateglinide and telmisartan not only decreased fasting plasma insulin, triglycerides, and free fatty acid levels, but also improved the responses of blood glucose to insulin and subsequently reduced the decremental glucose areas under the curve in the ZF rats. Combination therapy also restored the decrease of plasma adiponectin levels in the ZF rats. Monotherapy with nateglinide or telmisartan alone didnot significantly improve these metabolic parameters. These observations demonstrate that combination therapy with nateglinide and telmisartan may improve the metabolic derangements by ameliorating early phase of insulin secretion as well as insulin resistance in ZF rats fed twice daily. Our present findings suggest that the combination therapy with nateglinide and telmisartan could be a promising therapeutic strategy for the treatment of the metabolic syndrome.

Effects of glucomannan/spirulina-surimi on liver oxidation and inflammation in Zucker rats fed atherogenic diets.

PubMed

Vázquez-Velasco, Miguel; González-Torres, Laura; López-Gasco, Patricia; Bastida, Sara; Benedí, Juana; González-Muñoz, María José; Sánchez-Muniz, Francisco J

2015-12-01

Cholesterolemia is associated with pro-oxidative and proinflammatory effects. Glucomannan- or glucomannan plus spirulina-enriched surimis were included in cholesterol-enriched high-saturated diets to test the effects on lipemia; antioxidant status (glutathione status, and antioxidant enzymatic levels, expressions and activities); and inflammation biomarkers (endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α)) in Zucker fa/fa rats. Groups of eight rats each received diet containing squid-surimi (C), squid-surimi cholesterol-enriched diet (HC), glucomannan-squid-surimi cholesterol-enriched diet (HG), or glucomannan-spirulina-squid-surimi cholesterol-enriched diet (HGS) over a period of 7 weeks. HC diet induced severe hyperlipemia, hepatomegalia, increased inflammation markers, and impaired antioxidant status significantly (at least p < 0.05) vs. C diet. HG diet decreased lipemia and liver size and normalized antioxidant status to C group levels, but increased TNF-α with respect to HC diet (p < 0.05). In general terms, 3 g/kg of spirulina in diet maintained the positive results observed in the HG diet but, in addition, increased inflammation index [eNOS/(eNOS + iNOS)] and decreased plasma TNF-α (both p < 0.05). In conclusion, glucomannan plus a small amount of spirulina blocks negative effects promoted by hypercholesterolemic diets. Although more studies are needed, present results suggest the utility of including glucomannan and/or spirulina as functional ingredients into fish derivates to be consumed by people on metabolic syndrome risk.

Matrix Metalloproteinase-9 Expression Is Enhanced in Renal Parietal Epithelial Cells of Zucker Diabetic Fatty Rats and Is Induced by Albumin in In Vitro Primary Parietal Cell Culture

PubMed Central

Zhang, Yuanyuan; George, Jasmine; Li, Yun; Olufade, Rebecca; Zhao, Xueying

2015-01-01

As a subfamily of matrix metalloproteinases (MMPs), gelatinases including MMP-2 and MMP-9 play an important role in remodeling and homeostasis of the extracellular matrix. However, conflicting results have been reported regarding their expression level and activity in the diabetic kidney. This study investigated whether and how MMP-9 expression and activity were changed in glomerular epithelial cells upon albumin overload. In situ zymography, immunostaining and Western blot for renal MMP gelatinolytic activity and MMP-9 protein expression were performed in Zucker lean and Zucker diabetic rats. Confocal microscopy revealed a focal increase in gelatinase activity and MMP-9 protein in the glomeruli of diabetic rats. Increased glomerular MMP-9 staining was mainly observed in hyperplastic parietal epithelial cells (PECs) expressing claudin-1 in the diabetic kidneys. Interestingly, increased parietal MMP-9 was often accompanied by decreased staining for podocyte markers (nephrin and podocalyxin) in the sclerotic area of affected glomeruli in diabetic rats. Additionally, urinary excretion of podocyte marker proteins was significantly increased in association with the levels of MMP-9 and albumin in the urine of diabetic animals. To evaluate the direct effect of albumin on expression and activity of MMP-9, primary cultured rat glomerular PECs were incubated with rat serum albumin (0.25 - 1 mg/ml) for 24 - 48 hrs. MMP-9 mRNA levels were significantly increased following albumin treatment. Meanwhile, albumin administration resulted in a dose-dependent increase in MMP-9 protein and activity in culture supernatants of PECs. Moreover, albumin activated p44/42 mitogen-activated protein kinase (MAPK) in PECs. Inhibition of p44/42 MAPK suppressed albumin-induced MMP-9 secretion from glomerular PECs. Taken together, we have demonstrated that an up-regulation of MMP-9 in activated parietal epithelium is associated with a loss of adjacent podocytes in progressive diabetic nephropathy

Prevalence of overweight, obesity, abdominal obesity and obesity-related risk factors in southern China.

PubMed

Hu, Lihua; Huang, Xiao; You, Chunjiao; Li, Juxiang; Hong, Kui; Li, Ping; Wu, Yanqing; Wu, Qinhua; Wang, Zengwu; Gao, Runlin; Bao, Huihui; Cheng, Xiaoshu

2017-01-01

The purpose of this study is to assess the prevalence of overweight/obesity, abdominal obesity and obesity-related risk factors in southern China. A cross-sectional survey of 15,364 participants aged 15 years and older was conducted from November 2013 to August 2014 in Jiangxi Province, China, using questionnaire forms and physical measurements. The physical measurements included body height, weight, waist circumference (WC), body fat percentage (BFP) and visceral adipose index (VAI). Multivariate logistic regression analysis was performed to evaluate the risk factors for overweight/obesity and abdominal obesity. The prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 7.9% (8.4% in males and 7.6% in females). The prevalence of abdominal obesity was 10.2% (8.6% in males and 11.3% in females). The prevalence of overweight/obesity was 37.1% in urban residents and 30.2% in rural residents, and this difference was significant (P < 0.001). Urban residents had a significantly higher prevalence of abdominal obesity than rural residents (11.6% vs 8.7%, P < 0.001). Among the participants with an underweight/normal body mass index (BMI), 1.3% still had abdominal obesity, 16.1% had a high BFP and 1.0% had a high VAI. Moreover, among obese participants, 9.7% had a low /normal WC, 0.8% had a normal BFP and 15.9% had a normal VAI. Meanwhile, the partial correlation analysis indicated that the correlation coefficients between VAI and BMI, VAI and WC, and BMI and WC were 0.700, 0.666, and 0.721, respectively. A multivariate logistic regression analysis indicated that being female and having a high BFP and a high VAI were significantly associated with an increased risk of overweight/obesity and abdominal obesity. In addition, living in an urban area and older age correlated with overweight/obesity. This study revealed that obesity and abdominal obesity, which differed by gender and age, are epidemic in southern China. Moreover, there

Obesity

MedlinePlus

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Prevalence of overweight, obesity, abdominal obesity and obesity-related risk factors in southern China

PubMed Central

Hu, Lihua; Huang, Xiao; You, Chunjiao; Li, Juxiang; Hong, Kui; Li, Ping; Wu, Yanqing; Wu, Qinhua; Wang, Zengwu; Gao, Runlin; Bao, Huihui

2017-01-01

Objectives The purpose of this study is to assess the prevalence of overweight/obesity, abdominal obesity and obesity-related risk factors in southern China. Methods A cross-sectional survey of 15,364 participants aged 15 years and older was conducted from November 2013 to August 2014 in Jiangxi Province, China, using questionnaire forms and physical measurements. The physical measurements included body height, weight, waist circumference (WC), body fat percentage (BFP) and visceral adipose index (VAI). Multivariate logistic regression analysis was performed to evaluate the risk factors for overweight/obesity and abdominal obesity. Results The prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 7.9% (8.4% in males and 7.6% in females). The prevalence of abdominal obesity was 10.2% (8.6% in males and 11.3% in females). The prevalence of overweight/obesity was 37.1% in urban residents and 30.2% in rural residents, and this difference was significant (P < 0.001). Urban residents had a significantly higher prevalence of abdominal obesity than rural residents (11.6% vs 8.7%, P < 0.001). Among the participants with an underweight/normal body mass index (BMI), 1.3% still had abdominal obesity, 16.1% had a high BFP and 1.0% had a high VAI. Moreover, among obese participants, 9.7% had a low /normal WC, 0.8% had a normal BFP and 15.9% had a normal VAI. Meanwhile, the partial correlation analysis indicated that the correlation coefficients between VAI and BMI, VAI and WC, and BMI and WC were 0.700, 0.666, and 0.721, respectively. A multivariate logistic regression analysis indicated that being female and having a high BFP and a high VAI were significantly associated with an increased risk of overweight/obesity and abdominal obesity. In addition, living in an urban area and older age correlated with overweight/obesity. Conclusion This study revealed that obesity and abdominal obesity, which differed by gender and age, are

Pulmonary function in obese vs non-obese cats.

PubMed

García-Guasch, Laín; Caro-Vadillo, Alicia; Manubens-Grau, Jordi; Carretón, Elena; Camacho, Aparecido A; Montoya-Alonso, José Alberto

2015-06-01

Obesity is a risk factor in the development of several respiratory diseases. Lung volumes tend to be decreased, especially expiratory reserve volume, increasing expiratory flow limitation during tidal breathing. Barometric whole-body plethysmography is a non-invasive pulmonary function test that allows a dynamic study of breathing patterns. The objective of this study was to compare pulmonary function variables between obese and non-obese cats through the use of barometric whole-body plethysmography. Nine normal-weight and six obese cats were placed in the plethysmograph chamber, and different respiratory variables were measured. There was a significant decrease in tidal volume per kilogram (P = 0.003), minute volume per kilogram (P = 0.001) and peak inspiratory and expiratory flows per kilogram (P = 0.001) in obese cats compared with non-obese cats. Obesity failed to demonstrate a significant increase in bronchoconstriction index variable enhanced pause (Penh), as previously reported in humans and dogs. The results show that feline obesity impairs pulmonary function in cats, although a significant increase in bronchoconstriction indexes was not observed. Non-invasive barometric whole-body plethysmography can help characterise mechanical dysfunction of the airways in obese cats. © ISFM and AAFP 2014.

Interactome of Obesity: Obesidome : Genetic Obesity, Stress Induced Obesity, Pathogenic Obesity Interaction.

PubMed

Geronikolou, Styliani A; Pavlopoulou, Athanasia; Cokkinos, Dennis; Chrousos, George

2017-01-01

Obesity is a chronic disease of increasing prevalence reaching epidemic proportions. Genetic defects as well as epigenetic effects contribute to the obesity phenotype. Investigating gene (e.g. MC4R defects)-environment (behavior, infectious agents, stress) interactions is a relative new field of great research interest. In this study, we have made an effort to create an interactome (henceforth referred to as "obesidome"), where extrinsic stressors response, intrinsic predisposition, immunity response to inflammation and autonomous nervous system implications are integrated. These pathways are presented in one interactome network for the first time. In our study, obesity-related genes/gene products were found to form a complex interactions network.

In Vivo Cannabidiol Treatment Improves Endothelium-Dependent Vasorelaxation in Mesenteric Arteries of Zucker Diabetic Fatty Rats

PubMed Central

Wheal, Amanda J.; Jadoon, Khalid; Randall, Michael D.; O’Sullivan, Saoirse E.

2017-01-01

Background and purpose: We have shown that in vitro treatment with cannabidiol (CBD, 2 h) enhances endothelial function in arteries from Zucker diabetic fatty (ZDF) rats, partly due to a cyclooxygenase (COX)-mediated mechanism. The aim of the present study was to determine whether treatment with CBD in vivo would also enhance endothelial function. Experimental approach: Male ZDF rats, or ZDF Lean rats, were treated for 7 days (daily i.p. injection) with either 10mg/kg CBD or vehicle (n = 6 per group). Sections of mesenteric resistance arteries, femoral arteries and thoracic aortae were mounted on a wire myograph, and cumulative concentration-response curves to endothelium-dependent (acetylcholine, ACh, 1 nM–100 μM) or endothelium-independent (sodium nitroprusside, SNP, 1 nM–100 μM) agents were constructed. Multiplex analysis was used to measure serum metabolic and cardiovascular biomarkers. Key results: Vasorelaxation to ACh was significantly enhanced in mesenteric arteries from CBD-treated ZDF rats, but not ZDF Lean rats. The enhanced vasorelaxation in ZDF mesenteric arteries was no longer observed after COX inhibition using indomethacin or nitric oxide (NO) inhibition using L-NAME. Increased levels of serum c-peptide, insulin and intracellular adhesion molecule-1 observed in the ZDF compared to ZDF Lean rats were no longer significant after 7 days CBD treatment. Conclusion and implications: Short-term in vivo treatment with CBD improves ex vivo endothelium-dependent vasorelaxation in mesenteric arteries from ZDF rats due to COX- or NO-mediated mechanisms, and leads to improvements in serum biomarkers. PMID:28572770

Laparoscopic colectomy in the obese, morbidly obese, and super morbidly obese: when does weight matter?

PubMed

Champagne, Bradley J; Nishtala, Madhuri; Brady, Justin T; Crawshaw, Benjamin P; Franklin, Morris E; Delaney, Conor P; Steele, Scott R

2017-10-01

Previous studies have demonstrated that obese patients (BMI >30) undergoing laparoscopic colectomy have longer operative times and increased complications when compared to non-obese cohorts. However, there is little data that specifically evaluates the outcomes of obese patients based on the degree of their obesity. The aim of this study was to evaluate the impact of increasing severity of obesity on patients undergoing laparoscopic colectomy. A retrospective review was performed of all patients undergoing laparoscopic colectomy between 1996 and 2013. Patients were classified according to their BMI as obese (BMI 30.0-39.9), morbidly obese (BMI 40.0-49.9), and super obese (BMI >50). Main outcome measures included conversion rate, operative time, estimated blood loss, post-operative complications, and length of stay. There were 923 patients who met inclusion criteria. Overall, 604 (65.4%), 257 (27.9%), and 62 (6.7%) were classified as obese (O), morbidly obese (MO), and super obese (SO), respectively. Clinicopathologic characteristics were similar among the three groups. The SO group had significantly higher conversion rates (17.7 vs. 7 vs. 4.8%; P = 0.031), longer average hospital stays (7.1 days vs. 4.9 vs. 3.4; P = 0.001), higher morbidity (40.3 vs. 16.3 vs. 12.4%; P = 0.001), and longer operative times (206 min vs. 184 vs. 163; P = 0.04) compared to the MO and O groups, respectively. The anastomotic leak rate in the SO (4.8%; P = 0.027) and MO males (4.1%; P = 0.033) was significantly higher than MO females (2.2%) and all obese patients (1.8%). Increasing severity of obesity is associated with worse perioperative outcomes following laparoscopic colectomy.

Obesity and the obesity paradox in heart failure.

PubMed

Gupta, Pritha P; Fonarow, Gregg C; Horwich, Tamara B

2015-02-01

Obesity has reached epidemic proportions in the general population and is associated with an increased risk for the development of new-onset heart failure (HF). However, in acute and chronic HF, overweight and mild to moderate obesity is associated with substantially improved survival compared with normal weight. This phenomenon has been termed the "obesity paradox" in HF. The majority of data pertaining to the obesity paradox identifies obesity with body mass index; however, the reliability of this method has been questioned. Newer studies have explored the use of other measures of body fat and body composition, including waist circumference, waist-to-hip ratio, skinfold thickness, and bioelectrical impedance analysis of body composition. The relationship between the obesity paradox and cardiorespiratory fitness in HF is also discussed in this review, and we explore the various potential explanations for the obesity paradox and summarize the current evidence and guidelines for intentional weight loss treatments for HF in the obese population. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Dynamic model predicting overweight, obesity, and extreme obesity prevalence trends.

PubMed

Thomas, Diana M; Weedermann, Marion; Fuemmeler, Bernard F; Martin, Corby K; Dhurandhar, Nikhil V; Bredlau, Carl; Heymsfield, Steven B; Ravussin, Eric; Bouchard, Claude

2014-02-01

Obesity prevalence in the United States appears to be leveling, but the reasons behind the plateau remain unknown. Mechanistic insights can be provided from a mathematical model. The objective of this study is to model known multiple population parameters associated with changes in body mass index (BMI) classes and to establish conditions under which obesity prevalence will plateau. A differential equation system was developed that predicts population-wide obesity prevalence trends. The model considers both social and nonsocial influences on weight gain, incorporates other known parameters affecting obesity trends, and allows for country specific population growth. The dynamic model predicts that: obesity prevalence is a function of birthrate and the probability of being born in an obesogenic environment; obesity prevalence will plateau independent of current prevention strategies; and the US prevalence of overweight, obesity, and extreme obesity will plateau by about 2030 at 28%, 32%, and 9% respectively. The US prevalence of obesity is stabilizing and will plateau, independent of current preventative strategies. This trend has important implications in accurately evaluating the impact of various anti-obesity strategies aimed at reducing obesity prevalence. Copyright © 2013 The Obesity Society.

Leptin- and Leptin Receptor-Deficient Rodent Models: Relevance for Human Type 2 Diabetes

PubMed Central

Wang, Bingxuan; P., Charukeshi Chandrasekera; Pippin, John J.

2014-01-01

Among the most widely used animal models in obesity-induced type 2 diabetes mellitus (T2DM) research are the congenital leptin- and leptin receptor-deficient rodent models. These include the leptin-deficient ob/ob mice and the leptin receptor-deficient db/db mice, Zucker fatty rats, Zucker diabetic fatty rats, SHR/N-cp rats, and JCR:LA-cp rats. After decades of mechanistic and therapeutic research schemes with these animal models, many species differences have been uncovered, but researchers continue to overlook these differences, leading to untranslatable research. The purpose of this review is to analyze and comprehensively recapitulate the most common leptin/leptin receptor-based animal models with respect to their relevance and translatability to human T2DM. Our analysis revealed that, although these rodents develop obesity due to hyperphagia caused by abnormal leptin/leptin receptor signaling with the subsequent appearance of T2DM-like manifestations, these are in fact secondary to genetic mutations that do not reflect disease etiology in humans, for whom leptin or leptin receptor deficiency is not an important contributor to T2DM. A detailed comparison of the roles of genetic susceptibility, obesity, hyperglycemia, hyperinsulinemia, insulin resistance, and diabetic complications as well as leptin expression, signaling, and other factors that confound translation are presented here. There are substantial differences between these animal models and human T2DM that limit reliable, reproducible, and translatable insight into human T2DM. Therefore, it is imperative that researchers recognize and acknowledge the limitations of the leptin/leptin receptor-based rodent models and invest in research methods that would be directly and reliably applicable to humans in order to advance T2DM management. PMID:24809394

Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes.

PubMed

Wang, Bingxuan; Chandrasekera, P Charukeshi; Pippin, John J

2014-03-01

Among the most widely used animal models in obesity-induced type 2 diabetes mellitus (T2DM) research are the congenital leptin- and leptin receptor-deficient rodent models. These include the leptin-deficient ob/ob mice and the leptin receptor-deficient db/db mice, Zucker fatty rats, Zucker diabetic fatty rats, SHR/N-cp rats, and JCR:LA-cp rats. After decades of mechanistic and therapeutic research schemes with these animal models, many species differences have been uncovered, but researchers continue to overlook these differences, leading to untranslatable research. The purpose of this review is to analyze and comprehensively recapitulate the most common leptin/leptin receptor-based animal models with respect to their relevance and translatability to human T2DM. Our analysis revealed that, although these rodents develop obesity due to hyperphagia caused by abnormal leptin/leptin receptor signaling with the subsequent appearance of T2DM-like manifestations, these are in fact secondary to genetic mutations that do not reflect disease etiology in humans, for whom leptin or leptin receptor deficiency is not an important contributor to T2DM. A detailed comparison of the roles of genetic susceptibility, obesity, hyperglycemia, hyperinsulinemia, insulin resistance, and diabetic complications as well as leptin expression, signaling, and other factors that confound translation are presented here. There are substantial differences between these animal models and human T2DM that limit reliable, reproducible, and translatable insight into human T2DM. Therefore, it is imperative that researchers recognize and acknowledge the limitations of the leptin/leptin receptor- based rodent models and invest in research methods that would be directly and reliably applicable to humans in order to advance T2DM management.

Predicting adult obesity from childhood obesity: a systematic review and meta-analysis.

PubMed

Simmonds, M; Llewellyn, A; Owen, C G; Woolacott, N

2016-02-01

A systematic review and meta-analysis was performed to investigate the ability of simple measures of childhood obesity such as body mass index (BMI) to predict future obesity in adolescence and adulthood. Large cohort studies, which measured obesity both in childhood and in later adolescence or adulthood, using any recognized measure of obesity were sought. Study quality was assessed. Studies were pooled using diagnostic meta-analysis methods. Fifteen prospective cohort studies were included in the meta-analysis. BMI was the only measure of obesity reported in any study, with 200,777 participants followed up. Obese children and adolescents were around five times more likely to be obese in adulthood than those who were not obese. Around 55% of obese children go on to be obese in adolescence, around 80% of obese adolescents will still be obese in adulthood and around 70% will be obese over age 30. Therefore, action to reduce and prevent obesity in these adolescents is needed. However, 70% of obese adults were not obese in childhood or adolescence, so targeting obesity reduction solely at obese or overweight children needs to be considered carefully as this may not substantially reduce the overall burden of adult obesity. © 2015 World Obesity.

Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins

PubMed Central

Walsh, Dustin R.; Nolin, Thomas D.

2015-01-01

Drug transporters govern the absorption, distribution, and elimination of pharmacologically active compounds. Members of the solute carrier and ATP binding-cassette drug transporter family mediate cellular drug uptake and efflux processes, thereby coordinating the vectorial movement of drugs across epithelial barriers. To exert their physiologic and pharmacological function in polarized epithelia, drug transporters must be targeted and stabilized to appropriate regions of the cell membrane (i.e., apical versus basolateral). Despite the critical importance of drug transporter membrane targeting, the mechanisms that underlie these processes are largely unknown. Several clinically significant drug transporters possess a recognition sequence that binds to PSD-95/Drosophila discs large/ZO-1 (PDZ) proteins. PDZ proteins, such as the Na+/H+ exchanger regulatory factor (NHERF) family, act to stabilize and organize membrane targeting of multiple transmembrane proteins, including many clinically relevant drug transporters. These PDZ proteins are normally abundant at apical membranes, where they tether membrane-delimited transporters. NHERF expression is particularly high at the apical membrane in polarized tissue such as intestinal, hepatic, and renal epithelia, tissues important to drug disposition. Several recent studies have highlighted NHERF proteins as determinants of drug transporter function secondary to their role in controlling membrane abundance and localization. Mounting evidence strongly suggests that NHERF proteins may have clinically significant roles in pharmacokinetics and pharmacodynamics of several pharmacologically active compounds and may affect drug action in cancer and chronic kidney disease. For these reasons, NHERF proteins represent a novel class of post-translational mediators of drug transport and novel targets for new drug development. PMID:26092975

Dynamic Model Predicting Overweight, Obesity, and Extreme Obesity Prevalence Trends

PubMed Central

Thomas, Diana M.; Weedermann, Marion; Fuemmeler, Bernard F.; Martin, Corby K.; Dhurandhar, Nikhil V.; Bredlau, Carl; Heymsfield, Steven B.; Ravussin, Eric; Bouchard, Claude

2013-01-01

Objective Obesity prevalence in the United States (US) appears to be leveling, but the reasons behind the plateau remain unknown. Mechanistic insights can be provided from a mathematical model. The objective of this study is to model known multiple population parameters associated with changes in body mass index (BMI) classes and to establish conditions under which obesity prevalence will plateau. Design and Methods A differential equation system was developed that predicts population-wide obesity prevalence trends. The model considers both social and non-social influences on weight gain, incorporates other known parameters affecting obesity trends, and allows for country specific population growth. Results The dynamic model predicts that: obesity prevalence is a function of birth rate and the probability of being born in an obesogenic environment; obesity prevalence will plateau independent of current prevention strategies; and the US prevalence of obesity, overweight, and extreme obesity will plateau by about 2030 at 28%, 32%, and 9%, respectively. Conclusions The US prevalence of obesity is stabilizing and will plateau, independent of current preventative strategies. This trend has important implications in accurately evaluating the impact of various anti-obesity strategies aimed at reducing obesity prevalence. PMID:23804487

Obesity and psoriasis: inflammatory nature of obesity, relationship between psoriasis and obesity, and therapeutic implications.

PubMed

Carrascosa, J M; Rocamora, V; Fernandez-Torres, R M; Jimenez-Puya, R; Moreno, J C; Coll-Puigserver, N; Fonseca, E

2014-01-01

Obesity, particularly abdominal obesity, is currently considered a chronic low-grade inflammatory condition that plays an active role in the development of the pathophysiologic phenomena responsible for metabolic syndrome and cardiovascular disease through the secretion of proinflammatory adipokines and cytokines. In recent years clear genetic, pathogenic, and epidemiologic links have been established between psoriasis and obesity, with important implications for health. The relationship between the 2 conditions is probably bidirectional, with obesity predisposing to psoriasis and psoriasis favoring obesity. Obesity also has important implications in the treatment of psoriasis, such as a greater risk of adverse effects with conventional systemic drugs and reduced efficacy and/or increased cost with biologic agents, for which dosage should be adjusted to the patient's weight. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Glucocorticoids as modulators in the control of feeding.

PubMed

Castonguay, T W

1991-01-01

Three sets of experiments have been conducted that suggest that adrenal glucocorticoids play a role in the long-term control of intake and in dietary preferences. First, obesity is dependent upon glucocorticoid-modulated metabolic pathways. Surgical or pharmacological manipulations in obese animals that eliminate or diminish corticosterone activity result in levels of intake, meal patterns, macronutrient self-selection and weight gain that revert to levels seen in lean controls. Glucocorticoid replacement of adrenalectomized genetically obese Zucker rats restores the phenotypic expression of the obese rat's genetic heritage: increased weight gain, increased fat and total daily caloric intake and adiposity are restored in a dose-dependent fashion. Second, the increased fat intake observed subsequent to fasting in Sprague-Dawley rats is correlated with an increase in circulating corticosterone. Adrenalectomy blocks the fat specific refeeding response, and corticosterone treatment of adrenalectomized rats restores the increase in fat, carbohydrate and protein observed during refeeding. Third, humans suffering from Cushing's Disease have an increased preference for dietary fat. Weight-matched but disease-free obese controls show only slight increases in fat preference when compared to normal weight controls.

Prevalence of Canine Obesity, Obesity-Related Metabolic Dysfunction, and Relationship with Owner Obesity in an Obesogenic Region of Spain.

PubMed

Montoya-Alonso, J Alberto; Bautista-Castaño, Inmaculada; Peña, Cristina; Suárez, Lourdes; Juste, M Candelaria; Tvarijonaviciute, Asta

2017-01-01

The main objective of this study was to evaluate the prevalence of canine obesity and obesity-related metabolic dysfunction (ORMD) in the obesogenic area in Spain. The prevalence of overweight/obesity among owners of obese pets was also evaluated. In the sample population studied (93 client-owned dogs), 40.9% of dogs presented obesity (body condition score 7-9/9), 40.9% of dogs presented hypertension, 20.4% of dogs presented fasting hypertriglyceridemia, 20.4% fasting hypercholesterolemia, and 5.4% of dogs presented fasting hyperglycemia. The overall prevalence of ORMD was of 22.6%. Seventy-eight percent of overweight/obese owners had overweight/obese dogs ( P  < 0.001) including all dogs diagnosed with ORMD. In conclusion, in the studied obesogenic region of Spain, the prevalence of canine obesity and ORMD was shown to be elevated and related to the presence of overweight/obesity in owners. All dogs with ORMD were owned by overweight/obese persons. These results provide new inputs for future studies highlighting the relationship between owner and pet obesity and indicating the need of further efforts to control and reduce obesity prevalence in both.

Obesity and Anesthesia

MedlinePlus

... Resources About Policymakers Media ASA Member Toolkit Risks Obesity Explore this page: Obesity How does being overweight ... What you can do to reduce your risk? Obesity More than one-third of Americans are obese ...

Cancer and Obesity

MedlinePlus

... Kit Read the MMWR Science Clips Cancer and obesity Overweight and obesity are associated with cancer Language: ... a cancer associated with overweight and obesity. Problem Obesity is a leading cancer risk factor. What’s happening? ...

Does maternal obesity have an influence on feeding behavior of obese children?

PubMed

Cebeci, A N; Guven, A

2015-12-01

Although the pathogenesis of childhood obesity is multi factorial, maternal obesity and parenting have major roles. The aim of this study was to evaluate the influence of maternal obesity on feeding practices toward their obese school children. Obese children and adolescents referred to the pediatric endocrinology department were enrolled consecutively. Height and weight of all children and their mothers were measured. Maternal feeding practices were measured using an adapted version of the Child Feeding Questionnaire (CFQ). Answers were compared between obese (Body Mass Index [BMI] ≥ 30 kg/m2) and non-obese mothers. A total of 491 obese subjects (292 girls, mean age 12.0 ± 2.8 years) and their mothers participated in this study. A direct correlation between children's BMI and their mothers' BMI was found (P<0.001) both in girls (r = 0.372) and boys (r = 0.337). While 64.4% of mothers were found obese in the study, only half of them consider themselves as obese. No difference were found in the scores of the subscales "perceived responsibility", "restriction", "concern for child's weight" and "monitoring" between obese and non-obese mothers. Child's BMI-SDS positively correlated with mothers' personal weight perception, concern for child's weight and restriction after adjustment for child's age (P < 0.001, P = 0.012 and P = 0.002, respectively). Mothers' BMI highly correlate with children's BMI-z-scores. The degree of child's obesity increases mothers' concern and food restriction behavior. While mothers of obese children have a high prevalence of obesity, maternal obesity was found to have no significant influence on feeding behavior of obese school children.

Are there healthy obese?

PubMed

Griera Borrás, José Luis; Contreras Gilbert, José

2014-01-01

It is currently postulated that not all obese individuals have to be considered as pathological subjects. From 10% to 20% of obese people studied do not show the metabolic changes common in obese patients. The term "healthy obese" has been coined to refer to these patients and differentiate them from the larger and more common group of pathological obese subjects. However, the definition of "healthy obese" is not clear. Use of "healthy obese" as a synonym for obese without metabolic complications is risky. Clinical markers such as insulin resistance are used to identify this pathology. It is not clear that healthy obese subjects have lower morbidity and mortality than pathologically obese patients. According to some authors, healthy obese would represent an early stage in evolution towards pathological obesity. There is no agreement as to the need to treat healthy obese subjects. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Environmental Perturbations: Obesity

PubMed Central

Shore, Stephanie A.

2014-01-01

Obesity currently affects about one third of the U.S. population, while another one third is overweight. The importance of obesity for certain conditions such as heart disease and type 2 diabetes is well appreciated. The effects of obesity on the respiratory system have received less attention and are the subject of this chapter. Obesity alters the static mechanic properties of the respiratory system leading to a reduction in the functional residual capacity (FRC) and the expiratory reserve volume (ERV). There is substantial variability in the effects of obesity on FRC and ERV, at least some of which is related to the location, rather than the total mass of adipose tissue. Obesity also results in airflow obstruction, which is only partially attributable to breathing at low lung volume, and can also promote airway hyperresponsiveness and asthma. Hypoxemia is common is obesity, and correlates well with FRC, as well as with measures of abdominal obesity. However, obese subjects are usually eucapnic, indicating that hypoventilation is not a common cause of their hypoxemia. Instead, hypoxemia results from ventilation perfusion mismatch caused by closure of dependent airways at FRC. Many obese subjects complain of dyspnea either at rest or during exertion, and the dyspnea score also correlates with reductions in FRC and ERV. Weight reduction should be encouraged in any symptomatic obese individual, since virtually all of the respiratory complications of obesity improve with even moderate weight loss. PMID:23737172

Association of adolescent obesity with risk of severe obesity in adulthood.

PubMed

The, Natalie S; Suchindran, Chirayath; North, Kari E; Popkin, Barry M; Gordon-Larsen, Penny

2010-11-10

Although the prevalence of obesity has increased in recent years, individuals who are obese early in life have not been studied over time to determine whether they develop severe obesity in adulthood, thus limiting effective interventions to reduce severe obesity incidence and its potentially life-threatening associated conditions. To determine incidence and risk of severe obesity in adulthood by adolescent weight status. A cohort of 8834 individuals aged 12 to 21 years enrolled in 1996 in wave II of the US National Longitudinal Study of Adolescent Health, followed up into adulthood (ages 18-27 years during wave III [2001-2002] and ages 24-33 years during wave IV [2007-2009]). Height and weight were obtained via anthropometry and surveys administered in study participants' homes using standardized procedures. New cases of adult-onset severe obesity were calculated by sex, race/ethnicity, and adolescent weight status. Sex-stratified, discrete time hazard models estimated the net effect of adolescent obesity (aged <20 years; body mass index [BMI] ≥95th percentile of the sex-specific BMI-for-age growth chart or BMI ≥30.0) on risk of severe obesity incidence in adulthood (aged ≥20 years; BMI ≥40.0), adjusting for race/ethnicity and age and weighted for national representation. In 1996, 79 (1.0%; 95% confidence interval [CI], 0.7%-1.4%) adolescents were severely obese; 60 (70.5%; 95% CI, 57.2%-83.9%) remained severely obese in adulthood. By 2009, 703 (7.9%; 95% CI, 7.4%-8.5%) non-severely obese adolescents had become severely obese in adulthood, with the highest rates for non-Hispanic black women. Obese adolescents were significantly more likely to develop severe obesity in young adulthood than normal-weight or overweight adolescents (hazard ratio, 16.0; 95% CI, 12.4-20.5). In this cohort, obesity in adolescence was significantly associated with increased risk of incident severe obesity in adulthood, with variations by sex and race/ethnicity.

Reminder Cards Improve Physician Documentation of Obesity But Not Obesity Counseling.

PubMed

Shungu, Nicholas; Miller, Marshal N; Mills, Geoffrey; Patel, Neesha; de la Paz, Amanda; Rose, Victoria; Kropa, Jill; Edi, Rina; Levy, Emily; Crenshaw, Margaret; Hwang, Chris

2015-01-01

Physicians frequently fail to document obesity and obesity-related counseling. We sought to determine whether attaching a physical reminder card to patient encounter forms would increase electronic medical record (EMR) assessment of and documentation of obesity and dietary counseling. Reminder cards for obesity documentation were attached to encounter forms for patient encounters over a 2-week intervention period. For visits in the intervention period, the EMR was retrospectively reviewed for BMI, assessment of "obesity" or "morbid obesity" as an active problem, free-text dietary counseling within physician notes, and assessment of "dietary counseling" as an active problem. These data were compared to those collected through a retrospective chart review during a 2-week pre-intervention period. We also compared physician self-report of documentation via reminder cards with EMR documentation. We found significant improvement in the primary endpoint of assessment of "obesity" or "morbid obesity" as an active problem (42.5% versus 28%) compared to the pre-intervention period. There was no significant difference in the primary endpoints of free-text dietary counseling or assessment of "dietary counseling" as an active problem between the groups. Physician self-reporting of assessment of "obesity" or "morbid obesity" as an active problem (77.7% versus 42.5%), free-text dietary counseling on obesity (69.1% versus 35.4%) and assessment of "dietary counseling" as an active problem (54.3% versus 25.2%) were all significantly higher than those reflected in EMR documentation. This study demonstrates that physical reminder cards are a successful means of increasing obesity documentation rates among providers but do not necessarily increase rates of obesity-related counseling or documentation of counseling. Our study suggests that even with such interventions, physicians are likely under-documenting obesity and counseling compared to self-reported rates.

Obesity and government.

PubMed

Kahan, Scott; Zvenyach, Tracy

2016-10-01

Despite much effort, obesity prevalence and disease severity continues to worsen. The purpose of this review is to describe the leading government supported food and nutrition interventions and policies to prevent and address obesity in the USA. The review also summarizes obesity interventions and policies that the government plays a role in, but further development is warranted. The government's role in obesity has largely focused on interventions and policies such as national surveillance, obesity education and awareness, grant-based food subsidy programs, zoning for food access, school-based nutrition programs, dietary guidelines, nutrition labeling, and food marketing and pricing policies. The government has played a lesser role in obesity interventions and policies that provide access to evidence-based obesity care to people affected by the disease. Given the magnitude of the obesity epidemic, the government should explore multiple evidence-based interventions and policies across prevention and clinical care.

Protective effects of polyphenol-rich infusions from carob (Ceratonia siliqua) leaves and cladodes of Opuntia ficus-indica against inflammation associated with diet-induced obesity and DSS-induced colitis in Swiss mice.

PubMed

Aboura, Ikram; Nani, Abdelhafid; Belarbi, Meriem; Murtaza, Babar; Fluckiger, Aurélie; Dumont, Adélie; Benammar, Chahid; Tounsi, Moufida Saidani; Ghiringhelli, François; Rialland, Mickaël; Khan, Naim Akhtar; Hichami, Aziz

2017-12-01

In the present study, we have investigated the effects of polyphenol-rich infusions from carob leaves and OFI-cladodes on inflammation associated with obesity and dextran sulfate sodium (DSS)-induced ulcerative colitis in Swiss mice. In vitro studies revealed that aqueous extracts of carob leaves and OFI-cladodes exhibited anti-inflammatory properties marked by the inhibition of IL-6, TNF-α and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells concomitant with NF-κβ nucleus translocation inhibition. For in vivo investigations, Swiss male mice were subjected to control or high fat diet (HFD). At the 8th week after the start of study, animals received or not 1% infusion of either carob leaves or OFI-cladode for 4 weeks and were subjected to 2% DSS administration in drinking water over last 7 days. After sacrifice, pro-inflammatory cytokines levels in plasma and their mRNA expression in different organs were determined. Results showed that carob leaf and OFI-cladode infusions reduced inflammation severity associated with HFD-induced obesity and DSS-induced acute colitis indicated by decrease in pro-inflammatory cytokines expression (as such TNF-α, IL1b and IL-6) in colon, adipose tissue and spleen. In addition, plasma levels of IL-6 and TNF-α were also curtailed in response to infusions treatment. Thus, carob leaf and OFI-cladode infusions prevented intestinal permeability through the restoration of tight junction proteins (Zo1, occludins) and immune homeostasis. Hence, the anti-inflammatory effect of carob leaves and OFI-cladodes could be attributed to their polyphenols which might alleviate inflammation severity associated with obesity and colitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Obesity

MedlinePlus

Obesity means having too much body fat. It is different from being overweight, which means weighing too ... what's considered healthy for his or her height. Obesity happens over time when you eat more calories ...

Thioredoxin-mimetic peptide CB3 lowers MAPKinase activity in the Zucker rat brain☆

PubMed Central

Cohen-Kutner, Moshe; Khomsky, Lena; Trus, Michael; Ben-Yehuda, Hila; Lenhard, James M.; Liang, Yin; Martin, Tonya; Atlas, Daphne

2014-01-01

Diabetes is a high risk factor for dementia. High glucose may be a risk factor for dementia even among persons without diabetes, and in transgenic animals it has been shown to cause a potentiation of indices that are pre-symptomatic of Alzheimer's disease. To further elucidate the underlying mechanisms linking inflammatory events elicited in the brain during oxidative stress and diabetes, we monitored the activation of mitogen-activated kinsase (MAPKs), c-jun NH2-terminal kinase (JNK), p38 MAP kinases (p38MAPK), and extracellular activating kinsae1/2 (ERK1/2) and the anti-inflammatory effects of the thioredoxin mimetic (TxM) peptides, Ac-Cys-Pro-Cys-amide (CB3) and Ac-Cys-Gly-Pro-Cys-amide (CB4) in the brain of male leptin-receptor-deficient Zucker diabetic fatty (ZDF) rats and human neuroblastoma SH-SY5Y cells. Daily i.p. injection of CB3 to ZDF rats inhibited the phosphorylation of JNK and p38MAPK, and prevented the expression of thioredoxin-interacting-protein (TXNIP/TBP-2) in ZDF rat brain. Although plasma glucose/insulin remained high, CB3 also increased the phosphorylation of AMP-ribose activating kinase (AMPK) and inhibited p70S6K kinase in the brain. Both CB3 and CB4 reversed apoptosis induced by inhibiting thioredoxin reductase as monitored by decreasing caspase 3 cleavage and PARP dissociation in SH-SY5Y cells. The decrease in JNK and p38MAPK activity in the absence of a change in plasma glucose implies a decrease in oxidative or neuroinflammatory stress in the ZDF rat brain. CB3 not only attenuated MAPK phosphorylation and activated AMPK in the brain, but it also diminished apoptotic markers, most likely acting via the MAPK–AMPK–mTOR pathway. These results were correlated with CB3 and CB4 inhibiting inflammation progression and protection from oxidative stress induced apoptosis in human neuronal cells. We suggest that by attenuating neuro-inflammatory processes in the brain Trx1 mimetic peptides could become beneficial for preventing neurological

Obesity prevalence and accuracy of BMI-defined obesity in Russian firefighters.

PubMed

Gurevich, K G; Poston, W S C; Anders, B; Ivkina, M A; Archangelskaya, A; Jitnarin, N; Starodubov, V I

2017-01-01

No data exist on obesity or the accuracy of body mass index (BMI) in Russian Federation firefighters. To determine the prevalence of obesity and rates of misclassification of BMI-based obesity status. Career firefighters in the Moscow region completed anthropometric assessments including height, weight, BMI, body fat per cent (BF%) and waist circumference (WC). Using these three methods, we defined obesity as BMI ≥30, BF% >25 and WC >102, respectively. The study group consisted of 167 male firefighters. Obesity prevalence was 22% for BMI [95% confidence interval (CI) 16.9-28.5], 60% for BF% (95% CI 52.5-67.3) and 28% for WC (95% CI 21.3-34.9). False positive rates for BMI-based obesity status were low, with 3% (95% CI -1.1 to 7.1) and 6% (95% CI 1.6-9.9) of non-obese participants defined by BF% and WC standards misidentified as obese using BMI. However, 65% (95% CI 55.7-77.4) of BF%-defined obese participants and 36% (95% CI 22.5-49.9) of WC-defined obese participants were misclassified as non-obese using BMI (i.e. false negatives). Rates of BMI-based obesity in Russian male firefighters were similar to that of males in the general Russian adult male population. Compared with BF% or WC standards, BMI-based obesity classi- fication produced low rates of false positives but demonstrated high rates of false negatives. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Alcohol produces distinct hepatic lipidome and eicosanoid signature in lean and obese[S

PubMed Central

Puri, Puneet; Xu, Jun; Vihervaara, Terhi; Katainen, Riikka; Ekroos, Kim; Daita, Kalyani; Min, Hae-Ki; Joyce, Andrew; Mirshahi, Faridoddin; Tsukamoto, Hidekazu; Sanyal, Arun J.

2016-01-01

Alcohol- and obesity-related liver diseases often coexist. The hepatic lipidomics due to alcohol and obesity interaction is unknown. We characterized the hepatic lipidome due to 1) alcohol consumption in lean and obese mice and 2) obesity and alcohol interactions. In the French-Tsukamoto mouse model, intragastric alcohol or isocaloric dextrose were fed with either chow (lean) or high-fat, high-cholesterol diet (obese). Four groups (lean, lean alcohol, obese, and obese alcohol) were studied. MS was performed for hepatic lipidomics, and data were analyzed. Alcohol significantly increased hepatic cholesteryl esters and diacyl­glycerol in lean and obese but was more pronounced in obese. Alcohol produced contrasting changes in hepatic phospholipids with significant enrichment in lean mice versus significant decrease in obese mice, except phosphatidylglycerol, which was increased in both lean and obese alcohol groups. Most lysophospholipids were increased in lean alcohol and obese mice without alcohol use only. Prostaglandin E2; 5-, 8-, and 11-hydroxyeicosatetraenoic acids; and 9- and 13-hydroxyoctadecadienoic acids were considerably increased in obese mice with alcohol use. Alcohol consumption produced distinct changes in lean and obese with profound effects of obesity and alcohol interaction on proinflammatory and oxidative stress-related eicosanoids. PMID:27020313

Obese children experience higher plantar pressure and lower foot sensitivity than non-obese.

PubMed

da Rocha, Emmanuel Souza; Bratz, Denise Tiane Klein; Gubert, Larissa Colaço; de David, Ana; Carpes, Felipe P

2014-08-01

Children obesity is a risk factor for several dysfunctions and diseases, with negative effects on the morphology of the locomotor system, plantar pressure and body stability. A relationship between postural control and sensorimotor information has been assumed. However, there is few data on the effects of children obesity on the availability of sensorial information from the foot during standing. Twenty obese and twenty non-obese children were evaluated for foot sensitivity and plantar pressure during unipedal and bipedal stance. Data were compared between obese and non-obese participants, between foot regions and between legs. Obese children experiences higher plantar pressure and have lower foot sensitivity than non-obese. Additionally, obese children had similar sensitivity for different foot regions, as compared to the non-obese. Children obesity negatively influences foot sensitivity. Bipedal stance seemed more sensitive to differentiate between obese and non-obese. Higher plantar pressure and lower foot sensitivity in obese children may affect performance of weight bearing activities, contribute to higher risk of foot injuries and have potential implication for children footwear design and clinical physical examination. Copyright © 2014 Elsevier Ltd. All rights reserved.

Peroxisome proliferator-activated receptor subtype-specific regulation of hepatic and peripheral gene expression in the Zucker diabetic fatty rat.

PubMed

Dana, S L; Hoener, P A; Bilakovics, J M; Crombie, D L; Ogilvie, K M; Kauffman, R F; Mukherjee, R; Paterniti, J R

2001-08-01

Fibrates and thiazolidinediones are used clinically to treat hypertriglyceridemia and hyperglycemia, respectively. Fibrates bind to the peroxisome proliferator-activated receptor (PPAR)-alpha, and thiazolidinediones are ligands of PPAR-gamma. These intracellular receptors form heterodimers with retinoid X receptor to modulate gene transcription. To elucidate the target genes regulated by these compounds, we treated Zucker diabetic fatty rats (ZDF) for 15 days with a PPAR-alpha-specific compound, fenofibrate, a PPAR-gamma-specific ligand, rosiglitazone, and a PPAR-alpha/-gamma coagonist, GW2331, and measured the levels of several messenger RNAs (mRNAs) in liver by real-time polymerase chain reaction. All 3 compounds decreased serum glucose and triglyceride levels. Fenofibrate and GW2331 induced expression of acyl-coenzyme A (CoA) oxidase and enoyl-CoA hydratase and reduced apolipoprotein C-III and phosphoenolpyruvate carboxykinase mRNAs. Rosiglitazone modestly increased apolipoprotein C-III mRNA and had no effect on expression of the other 2 genes in the liver but increased the expression of glucose transporter 4 and phosphoenolpyruvate carboxykinase in adipose tissue. We identified a novel target in liver, mitogen-activated phosphokinase phosphatase 1, whose down-regulation by PPAR-alpha agonists may improve insulin sensitivity in that tissue by prolonging insulin responses. The results of these studies suggest that activation of PPAR-alpha as well as PPAR-gamma in therapy for type 2 diabetes will enhance glucose and triglyceride control by combining actions in hepatic and peripheral tissues. Copyright 2001 by W.B. Saunders Company

Employment discrimination against obese women in obesity clinic's patients perspective.

PubMed

Obara-Gołębiowska, Małgorzata

2016-01-01

The workplace is one of many areas of life where obese people are unfairly treated. According to the literature obese women are particularly susceptible to discrimination in employment. There is a lack of polish researches of this subject. The main objective of this study was to analyze personal, subjective experiences related to weight bias and discrimination against obese people in the workplace of obese Polish women. The study was carried out in a hospital clinic for obesity management. A total of 420 women with BMI>30, aged 21 to 72, participated in group interviews focused on the weight bias and discrimination against obese people in the workplace. In the group of clinically obese women, 5.3% of subjects had experienced employment discrimination and 10.5% had been victims of verbal and social abuse in the workplace. The most common psycho-physical consequences of the weight stigma were emotional problems, lack of motivation and overeating in response to stress. Weight-based discrimination in the workplace poses a problem in Poland. The weight stigma and occupational discrimination lead to psycho-physical discomfort which exacerbates overeating and obesity.

Robot-assisted total laparoscopic hysterectomy in obese and morbidly obese women.

PubMed

Rebeles, Sonia A; Muntz, Howard G; Wieneke-Broghammer, Carrie; Vason, Emily S; McGonigle, Kathryn F

2009-10-01

Total laparoscopic hysterectomy (TLH) in obese patients is challenging. We sought to evaluate whether total laparoscopic hysterectomies using the da Vinci robotic system in obese patients, in comparison with non-obese patients, is a reasonable surgical approach. One-hundred consecutive robot-assisted TLHs were performed over a 17-month period. Obesity was not a contraindication to robotic surgery, assuming adequate respiratory function to tolerate Trendelenburg position and, for cancer cases, a small enough uterus to allow vaginal extraction without morcellation. Data were prospectively collected on patient characteristics, total operative time, hysterectomy time, estimated blood loss, length of stay, and complications. Outcomes with non-obese and obese women were compared. The median age, weight, and BMI of the 100 patients who underwent robot-assisted TLH was 57.6 years (30.0-90.6), 82.1 kg (51.9-159.6), and 30.2 kg/m(2) (19.3-60.2), respectively. Fifty (50%) patients were obese (BMI ≥ 30); 22 patients were morbidly obese (BMI ≥ 40). There was no increase in complications (p = 0.56) or blood loss (p = 0.44) with increasing BMI. While increased BMI was associated with longer operative times (p = 0.05), median time increased by only 36 min when comparing non-obese and morbidly obese patients. Median length of stay was one day for all weight categories (p = 0.42). Robot-assisted TLH is feasible and can be safely performed in obese patients. More data are needed to compare robot-assisted TLH with other hysterectomy techniques in obese patients. Nonetheless, our results are encouraging. Robot-assisted total laparoscopic hysterectomy may be the preferred technique for appropriately selected obese patients.

Measuring Socioeconomic Inequality in Obesity: Looking Beyond the Obesity Threshold.

PubMed

Bilger, Marcel; Kruger, Eliza J; Finkelstein, Eric A

2017-08-01

We combine two of the most widely used measures in the inequality and poverty literature, the concentration index and Foster-Greer-Thorbecke metric to the analysis of socioeconomic inequality in obesity. This enables us to describe socioeconomic inequality not only in obesity status but also in its depth and severity. We apply our method to 1971-2012 US data and show that while the socioeconomic inequality in obesity status has now almost disappeared, this is not the case when depth and severity of obesity are considered. Such socioeconomic gradient is found to be greatest among non-Hispanic whites, but decomposition analysis also reveals an inverse relationship between income and obesity outcomes among Mexican Americans once the effect of immigrant status has been accounted for. The socioeconomic gradient is also greater among women with marital status further increasing it for severity of obesity while the opposite is true among men. Overall, the socioeconomic gradient exists as poorer individuals lie further away from the obesity threshold. Our study stresses the need for policies that jointly consider obesity and income to support those who suffer from the double burden of poverty and obesity-related health conditions. © 2016 The Authors. Health Economics Published by John Wiley & Sons Ltd. © 2016 The Authors. Health Economics Published by John Wiley & Sons Ltd.

Biology of obesity: lessons from animal models of obesity.

PubMed

Kanasaki, Keizo; Koya, Daisuke

2011-01-01

Obesity is an epidemic problem in the world and is associated with several health problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

Medical implications of obesity in horses--lessons for human obesity.

PubMed

Johnson, Philip J; Wiedmeyer, Charles E; Messer, Nat T; Ganjam, Venkataseshu K

2009-01-01

There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. © Diabetes Technology Society

Medical Implications of Obesity in Horses—Lessons for Human Obesity

PubMed Central

Johnson, Philip J.; Wiedmeyer, Charles E.; Messer, Nat T.; Ganjam, Venkataseshu K.

2009-01-01

There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. PMID:20046661

Measuring Socioeconomic Inequality in Obesity: Looking Beyond the Obesity Threshold

PubMed Central

Kruger, Eliza J.; Finkelstein, Eric A.

2016-01-01

Abstract We combine two of the most widely used measures in the inequality and poverty literature, the concentration index and Foster–Greer–Thorbecke metric to the analysis of socioeconomic inequality in obesity. This enables us to describe socioeconomic inequality not only in obesity status but also in its depth and severity. We apply our method to 1971–2012 US data and show that while the socioeconomic inequality in obesity status has now almost disappeared, this is not the case when depth and severity of obesity are considered. Such socioeconomic gradient is found to be greatest among non‐Hispanic whites, but decomposition analysis also reveals an inverse relationship between income and obesity outcomes among Mexican Americans once the effect of immigrant status has been accounted for. The socioeconomic gradient is also greater among women with marital status further increasing it for severity of obesity while the opposite is true among men. Overall, the socioeconomic gradient exists as poorer individuals lie further away from the obesity threshold. Our study stresses the need for policies that jointly consider obesity and income to support those who suffer from the double burden of poverty and obesity‐related health conditions. © 2016 The Authors. Health Economics Published by John Wiley & Sons Ltd. PMID:27515829

Tissue Oxygenation in Obese and Non-obese Patients During Laparoscopy

PubMed Central

Fleischmann, Edith; Kurz, Andrea; Niedermayr, Monika; Schebesta, Karl; Kimberger, Oliver; Prager, Gerhard; Sessler, Daniel I.; Kabon, Barbara

2005-01-01

Background: Wound infection risk is inversely related to subcutaneous oxygenation, which is reduced in obese patients and may be reduced even more during laparoscopic procedures. Methods: We evaluated subcutaneous tissue oxygenation (PsqO2) in 20 patients with a body mass index (BMI) ≥40 kg·m–2 (obese) and 15 patients with BMI <30 kg·m-2 (non-obese) undergoing laparoscopic surgery with standardised anaesthesia technique and fluid administration. Arterial oxygen tension was maintained near 150 mmHg. PsqO2 was measured from a surrogate wound on the upper arm. Data were analyzed with unpaired two-tailed t or Wilcoxon rank-sum tests; P < 0.05 was statistically significant. Data are given as mean (SD). Results: An FIO2 of 51% (13%) was required in obese patients to reach an arterial oxygen tension of 150 mmHg; however, an FIO2 of only 40% (7%) was required to reach the same oxygen tension in non-obese patients (P=0.007). PsqO2 was significantly less in obese patients: 41 (10) vs. 57 (15) mmHg (P<0.001). Conclusion: Obesity reduces the amount of inspired oxygen required to obtain a given arterial partial pressure and tissue oxygenation. Both factors probably contribute to high infection risk in obese patients. PMID:15978153

Obesity and bone.

PubMed

Compston, Juliet

2013-03-01

Recent studies indicate that fractures in obese postmenopausal women and older men contribute significantly to the overall fracture burden. The effect of obesity is to some extent site-dependent, the risk being increased for some fractures and decreased for others, possibly related to different patterns of falling and the presence or absence of soft tissue padding. Risk factors for fracture in obese individuals appear to be similar to those in the nonobese population, although falls may be particularly important in the obese. There is some evidence that the morbidity associated with fractures in obese individuals is greater than in the nonobese; however, a recent study indicates that the mortality associated with fracture is lower in obese and overweight people than in those of normal weight. The evidence base for strategies to prevent fractures in obese individuals is weak and is an important area for future research.

Childhood Obesity, Obesity Treatment Outcome, and Achieved Education: A Prospective Cohort Study.

PubMed

Hagman, Emilia; Danielsson, Pernilla; Brandt, Lena; Svensson, Viktoria; Ekbom, Anders; Marcus, Claude

2017-10-01

Childhood obesity represents a social burden. This study aims to investigate whether achieved educational level differs in young adults who have suffered obesity in childhood compared with the general population and to determine how obesity treatment influences achieved educational level. This prospective cohort study includes subjects from the Swedish Childhood Obesity Treatment Registry (BORIS, n = 1,465) who were followed up after 20 years of age. They were compared with a randomly selected matched population-based group (n = 6,979). Achieved educational level was defined as ≥12 years in school (completers). Covariates include sex, migration background, and attention deficit disorders for both groups. Furthermore, age and degree of obesity at start of obesity treatment, treatment duration, and efficacy were analyzed in the obese cohort. In the obese cohort, 55.4% were school completers, compared with 76.2% in the comparison group (adjusted odds ratio [OR] = .42, p < .0001). Subjects with moderate obesity had a completion rate of 64.4%, compared with 50.9% among subjects with morbid obesity (adjusted OR = .57, p < .0001). Successful obesity treatment was associated with increased future educational level, compared with those experiencing no treatment effect (61.9% vs. 51.3% completers; adjusted OR = 1.4, p < .05). In children with attention deficit disorder, obesity was not an extra risk for not completing 12 or more years of schooling, p = .11. Obesity in childhood was associated with low educational level in early adulthood. Children and adolescents with obesity may require special support at school in addition to health care treatment to lose weight. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Required friction during overground walking is lower among obese compared to non-obese older men, but does not differ with obesity among women.

PubMed

Arena, Sara L; Garman, Christina R; Nussbaum, Maury A; Madigan, Michael L

2017-07-01

Obesity and aging have been independently associated with altered required friction during walking, but it is unclear how these factors interact to influence the likelihood of slipping. Therefore, the purpose of this study was to determine whether there are differences related to obesity and aging on required friction during overground walking. Fourteen older non-obese, 11 older obese, 20 younger non-obese, and 20 younger obese adults completed walking trials at both a self-selected and hurried speed. When walking at a hurried speed, older obese men walked at a slower gait speed and exhibited lower frictional demands compared both to older non-obese men and to younger obese men. No differences in required friction were found between non-obese and obese younger adults. These results suggest that the increased rate of falls among obese or older adults is not likely due to a higher risk of slip initiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Who pays for obesity?

PubMed

Bhattacharya, Jay; Sood, Neeraj

2011-01-01

Adult obesity is a growing problem. From 1962 to 2006, obesity prevalence nearly tripled to 35.1 percent of adults. The rising prevalence of obesity is not limited to a particular socioeconomic group and is not unique to the United States. Should this widespread obesity epidemic be a cause for alarm? From a personal health perspective, the answer is an emphatic "yes." But when it comes to justifications of public policy for reducing obesity, the analysis becomes more complex. A common starting point is the assertion that those who are obese impose higher health costs on the rest of the population—a statement which is then taken to justify public policy interventions. But the question of who pays for obesity is an empirical one, and it involves analysis of how obese people fare in labor markets and health insurance markets. We will argue that the existing literature on these topics suggests that obese people on average do bear the costs and benefits of their eating and exercise habits. We begin by estimating the lifetime costs of obesity. We then discuss the extent to which private health insurance pools together obese and thin, whether health insurance causes obesity, and whether being fat might actually cause positive externalities for those who are not obese. If public policy to reduce obesity is not justified on the grounds of external costs imposed on others, then the remaining potential justification would need to be on the basis of helping people to address problems of ignorance or self-control that lead to obesity. In the conclusion, we offer a few thoughts about some complexities of such a justification.

Arginine-supplemented enteral nutrition in critically ill diabetic and obese rats: a dose-ranging study evaluating nutritional status and macrophage function.

PubMed

Bonhomme, Sandra; Belabed, Linda; Blanc, Marie-Céline; Neveux, Nathalie; Cynober, Luc; Darquy, Sylviane

2013-01-01

Critically ill diabetic and obese patients are at high risk of complications. Arginine availability is lowered in diabetes and in stress situations, yet arginine is necessary for immune response, mainly by its action through nitric oxide (NO). These facts argue for arginine-supplemented diets in critically ill patients. However, studies have raised concerns about possible adverse effects of such diets in intensive-care patients. We therefore analyzed the metabolic and immunologic effects of an arginine-enriched diet in stressed diabetic-obese rats. Zucker Diabetic Fatty rats (fa/fa) were made endotoxemic by an intraperitoneal injection of lipopolysaccharide and then fed 4-d enteral nutrition enriched with arginine (ARG group) or a non-essential amino acid mix (NEAA group). The two groups each were subdivided into three subgroups: the ARG subgroups received 0.5 g (ARG0.5), 2 g (ARG2), and 5 g (ARG5) of arginine per kilogram daily, and the NEAA groups were made isonitrogenous with the corresponding ARG subgroups (NEAA0.5, NEAA2, and NEAA5). Plasma and urinary biomarkers were measured. Cytokine and NO production levels and inducible NO synthase and arginase protein levels were determined from peritoneal macrophages. The survival rate was lower in the ARG5 and NEAA5 subgroups than in all the other subgroups. The nitrogen balance was higher in the ARG5 group than in the NEAA5 group. Plasma triacylglycerol levels were lower in the ARG2 group than in the NEAA2 group. Interleukin-6, tumor necrosis factor-α, and NO production in the macrophages decreased and arginase-1 was upregulated in the ARG-treated rats. In this model, mortality was increased by the nitrogen burden rather than by arginine per se. Arginine improved nitrogen balance and had an anti-inflammatory action on macrophages by regulating NO production, probably through arginase-1 expression. Copyright © 2013 Elsevier Inc. All rights reserved.

Childhood Obesity

ERIC Educational Resources Information Center

Yuca, Sevil Ari, Ed.

2012-01-01

This book aims to provide readers with a general as well as an advanced overview of the key trends in childhood obesity. Obesity is an illness that occurs due to a combination of genetic, environmental, psychosocial, metabolic and hormonal factors. The prevalence of obesity has shown a great rise both in adults and children in the last 30 years.…

Obesity treatment—more than food and exercise: a qualitative study exploring obese adolescents' and their parents' views on the former's obesity

PubMed Central

Lindelof, Anders; Nielsen, Claus Vinther; Pedersen, Birthe D.

2010-01-01

The aim of this study was to explore obese adolescents’ and their parents’ views on the former's obesity; especially to gain knowledge about barriers and motivational factors that influence obese adolescents’ ability to lose weight. This is a qualitative study involving field observation and semi-structured interviews with obese adolescents and their parents. The analysis takes a phenomenological–hermeneutic approach. Fifteen obese adolescents aged 13–16 years and their parents/grandparents participated in this study (one father, seven mothers, five sets of parents and two sets of grandparents). The results showed that obese adolescents’ are aware that they have unhealthy eating habits and they wish they were able to attain to a healthier diet. Although in poor physical shape, obese adolescents perceive their daily level of exercise as moderate. Obese adolescents blame themselves for being obese and blame their parents for an unhealthy diet, and for being unsupportive regarding exercise. Parents blame their obese child of lacking will power to change eating and exercise habits. As a consequence, the homely atmosphere is often characterised by quarrels and negative feelings. The conclusion is that despite obese adolescents’ intention of reducing weight, underlying issues interfere with this goal. This is particularly related to quarrels with parents, self-blame and misguided understanding of eating and exercising habits. These matters need to be addressed when treating obesity among adolescents. PMID:20640019

Disability associated with obesity, dynapenia and dynapenic-obesity in Chinese older adults.

PubMed

Yang, Ming; Ding, Xiang; Luo, Li; Hao, Qiukui; Dong, Birong

2014-02-01

Whether the combination of obesity and low muscle strength (dynapenic-obesity) would cause greater impairment of the activities of daily living (ADL)/instrumental activities of daily living (IADL) than obesity alone and low muscle strength alone (dynapenia) remains unclear. The aim of this study was to reveal the possible independent and additive effects of dynapenia and obesity on ADL/IADL disability in an older Chinese population. A cross-sectional study, including 616 community-dwelling older adults, was conducted in China from 2010 to 2012. Based on the World Health Organization Asian Criteria of Obesity and handgrip strength tertiles, 4 independent groups were identified as follows: nondynapenia/nonobesity, dynapenia alone, obesity alone, and dynapenic-obesity. The Katz Index of Independence in ADL was used to assess ADL disability, whereas 6 IADL items of the Older Americans Resources and Services (OARS) multidimensional functional assessment questionnaire were used to assess IADL disability. The prevalence of ADL and IADL disability was 21.1% and 28.9% in the dynapenic-obesity group, 15.5% and 22.6% in the dynapenia alone group, 13.1% and 19.6% in the obesity alone group, and 11.9% and 12.9% in the nondynapenia/nonobesity group, respectively. After adjusting for the covariates, in comparison with the dynapenic-obesity group, the adjusted odds ratios (95% confidence interval) for ADL disability were 0.36 (0.13-0.73) in the nondynapenia/nonobesity group, 0.51 (0.20-0.78) in the dynapenia-alone group, and 0.40 (0.11-0.61) in the obesity-alone group. The corresponding data for IADL disability were 0.55 (0.20-0.93), 0.82 (0.39-0.98), and 0.61 (0.30-0.91), respectively. Dynapenia, obesity, and dynapenic-obesity were associated with an increased risk of ADL/IADL disability. Dynapenic-obesity was associated with a greater risk of ADL/IADL disability in comparison with dynapenia or obesity alone. Copyright © 2014 American Medical Directors Association, Inc

The Association of Adolescent Obesity with Risk of Severe Obesity in Adulthood

PubMed Central

The, Natalie S.; Suchindran, Chirayath; North, Kari E.; Popkin, Barry M.; Gordon-Larsen, Penny

2010-01-01

Context Although the prevalence of obesity has increased in recent years, individuals who are obese early in life have not been followed over time to determine whether they develop severe obesity in adulthood, thus limiting effective interventions to reduce severe obesity incidence and its potentially life-threatening associated conditions. Objective A US nationally representative cohort was followed from adolescence through adulthood to determine incidence of severe obesity in adulthood and which groups are at highest risk. Design, Setting, and Participants Subjects included 8,834 individuals enrolled in wave II (1996: 12–21 y) of the National Longitudinal Study of Adolescent Health and followed into adulthood [wave III (2001–2002: 18–27 y), and wave IV (2007–2009: 24–33 y)]. Data come from measured height and weight obtained via anthropometry and surveys administered in study participants' homes using standardized procedures. Main Outcome Measures New cases of adult-onset severe obesity were calculated by sex, race/ethnicity, and adolescent weight status. Sex-stratified, discrete time hazard models estimated the net effect of adolescent obesity (<20 y, body mass index [BMI]≥95th percentile of the sex-specific BMI-for age growth chart or BMI≥30.0) on risk of severe obesity incidence in adulthood (≥20 y, BMI≥40.0), adjusting for race/ethnicity and age and weighted for national representation. Results In 1996, 1.0% (95% Confidence Interval [CI], 0.7%–1.4%; n=79) of adolescents were severely obese and 70.5% (95% CI, 57.2%–83.9%; n=60) remained severely obese in adulthood. By 2009, 7.9% (95% CI, 7.4%–8.5%; n=703) of non-severely obese adolescents became severely obese in adulthood, with highest rates for non-Hispanic black females. Obese adolescents were significantly (Hazard Ratio, 16.0; 95% CI, 12.4, 20.5) more likely to develop severe obesity in young adulthood than normal weight or overweight adolescents. Conclusions Obesity in adolescence

Obesity in America.

PubMed

Rosenthal, Raul J; Morton, John; Brethauer, Stacy; Mattar, Samer; De Maria, Eric; Benz, Jennifer K; Titus, Jennifer; Sterrett, David

2017-10-01

The prevalence of obesity in America continues to grow significantly. Awareness and understanding of the disease of obesity and treatment options for it appear to be lacking among the general US population. This study aimed to identify misperceptions in diagnosis and treatment of obesity, struggles Americans face in obtaining treatment, consequences of obesity, and perceived barriers to weight loss. University hospital, United States. A survey of 1509 adults was completed in September 2016 using AmeriSpeak, a probability-based panel designed to be representative of the US household population. The survey included oversamples of blacks and Hispanics. The study analyzed quantitative data from structured interviews and presents descriptive statistics related to public attitudes toward obesity. Of Americans, 81% consider obesity to be the most serious health problem facing the nation, tying cancer as the top issue and landing ahead of diabetes (72%), heart disease (72%), mental illness (65%), and HIV infection and AIDS (46%). Nearly all Americans (94%) agree that obesity itself, even when no other diseases are present, increases the risk for early death. Most Americans overestimate the effectiveness of some obesity treatments, such as diet and exercise alone. Many overweight and obese Americans do not consult a doctor at all about their issues of excess weight. There is increased awareness about the serious consequences of obesity, but there is still a lack of understanding about the reasons and best treatment modalities for the disease. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Childhood Obesity Facts

MedlinePlus

... and Local Programs Related Topics Diabetes Nutrition Childhood Obesity Facts Recommend on Facebook Tweet Share Compartir On ... Children (WIC) Program, 2000-2014 Prevalence of Childhood Obesity in the United States Childhood obesity is a ...

Obesity Hypoventilation Syndrome

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... Home / < Back To Health Topics / Obesity Hypoventilation Syndrome Obesity Hypoventilation Syndrome Also known as Pickwickian Syndrome What ... your neck is larger than normal. Complications of Obesity Hypoventilation Syndrome When left untreated, OHS can cause ...

Intergenerational impact of maternal obesity and postnatal feeding practices on pediatric obesity

PubMed Central

Thompson, Amanda L.

2014-01-01

The postnatal feeding practices of obese and overweight mothers may place their children at particular risk for the development of obesity through shared biology and family environments. This paper reviews the feeding practices of obese mothers, describes potential mechanisms linking maternal feeding behaviors to child obesity risk, and highlights potential avenues for intervention. This review documents that supporting breastfeeding, improving the food choices of obese women, and encouraging the development of feeding styles that are responsive to hunger and satiety cues are important for improving the quality of the eating environment and preventing the intergenerational transmission of obesity. PMID:24147925

Intergenerational impact of maternal obesity and postnatal feeding practices on pediatric obesity.

PubMed

Thompson, Amanda L

2013-10-01

The postnatal feeding practices of obese and overweight mothers may place their children at increased risk for the development of obesity through shared biology and family environments. This article reviews the feeding practices of obese mothers, describes the potential mechanisms linking maternal feeding behaviors to child obesity risk, and highlights the potential avenues of intervention. Strategies important for improving the quality of the eating environment and preventing the intergenerational transmission of obesity include supporting breastfeeding, improving the food choices of obese women, and encouraging the development of feeding styles that are responsive to hunger and satiety cues. © 2013 International Life Sciences Institute.

The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity

PubMed Central

Nielsen, Louise Aas; Nielsen, Tenna Ruest Haarmark; Holm, Jens-Christian

2015-01-01

The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD) complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events), and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring. PMID:26465142

Combined parental obesity augments single-parent obesity effects on hypothalamus inflammation, leptin signaling (JAK/STAT), hyperphagia, and obesity in the adult mice offspring.

PubMed

Ornellas, Fernanda; Souza-Mello, Vanessa; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

2016-01-01

We aimed to evaluate the effects of maternal and/or paternal obesity on offspring body mass, leptin signaling, appetite-regulating neurotransmitters and local inflammatory markers. C57BL/6 mice received standard chow (SC, lean groups) or high-fat diet (HF, obese groups) starting from one month of age. At three months, HF mice became obese relative to SC mice. They were then mated as follows: lean mother and lean father, lean mother and obese father, obese mother and lean father, and obese mother and obese father. The offspring received the SC diet from weaning until three months of age, when they were sacrificed. In the offspring, paternal obesity did not lead to changes in the Janus kinase (JAK)/signal transducer and activation of the transcription (STAT) pathway or feeding behavior but did induce hypothalamic inflammation. On the other hand, maternal obesity resulted in increased weight gain, hyperleptinemia, decreased leptin OBRb receptor expression, JAK/STAT pathway impairment, and increased SOCS3 signaling in the offspring. In addition, maternal obesity elevated inflammatory markers and altered NPY and POMC expression in the hypothalamus. Interestingly, combined parental obesity exacerbated the deleterious outcomes compared to single-parent obesity. In conclusion, while maternal obesity is known to program metabolic changes and obesity in offspring, the current study demonstrated that obese fathers induce hypothalamus inflammation in offspring, which may contribute to the development of metabolic syndromes in adulthood.

Treating Obesity As a Disease

MedlinePlus

... Obesity, And What You Can Do Understanding the American Obesity Epidemic Stress Management How Does Stress Affect You? ... Keeping the Weight Off • Obesity - Introduction - Understanding the American Obesity Epidemic - Treating Obesity as a Disease - Childhood Obesity ...

Disability and Obesity

MedlinePlus

... CDC Employees and Reasonable Accommodations (RA) Disability and Obesity Language: English (US) Español (Spanish) Recommend on Facebook ... and Disability at http://www.ncpad.org/ The Obesity Epidemic Obesity affects different people in different ways ...

Outcome following total knee arthroplasty in obese versus non-obese Asian patients.

PubMed

Goh, Graham Seow-Hng; Liow, Ming Han Lincoln; Mitra, Amit Kanta

2015-12-01

To compare the outcome following total knee arthroplasty (TKA) in obese and non-obese Asian patients. 27 obese patients were compared with 27 non-obese controls matched for age, gender, diagnosis (osteoarthritis), prosthesis, preoperative Knee Society knee and function scores, preoperative Oxford Knee Score, and follow-up duration. All TKAs were performed by a single surgeon. Patients were assessed at 6 months and 2 years for the range of motion, Knee Society knee and function scores, Oxford Knee Score, and Short Form-36 Health Survey (SF-36). The obese and non-obese groups did not differ significantly in pre- and post-operative variables: range of motion, Knee Society knee and function scores, Oxford Knee Score, and SF-36 score. Using revision as an end-point, implant survival was 100%. There were no intra- or post-operative complications in either group. Obese and non-obese Asian patients achieved a comparable outcome following TKA.

Calorie restriction attenuates cardiac remodeling and diastolic dysfunction in a rat model of metabolic syndrome.

PubMed

Takatsu, Miwa; Nakashima, Chieko; Takahashi, Keiji; Murase, Tamayo; Hattori, Takuya; Ito, Hiromi; Murohara, Toyoaki; Nagata, Kohzo

2013-11-01

Calorie restriction (CR) can modulate the features of obesity-related metabolic and cardiovascular diseases. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. DS/obese rats develop hypertension and manifest left ventricular remodeling and diastolic dysfunction, as well as increased cardiac oxidative stress and inflammation. We have now investigated the effects of CR on cardiac pathophysiology in DS/obese rats. DS/obese rats were fed either normal laboratory chow ad libitum or a calorie-restricted diet (65% of the average food intake for ad libitum) from 9 to 13 weeks. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean) littermates served as controls. CR reduced body weight in both DS/obese and DS/lean rats, as well as attenuated the development of hypertension in DS/obese rats without affecting blood pressure in DS/lean rats. CR also reduced body fat content, ameliorated left ventricular hypertrophy, fibrosis, and diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats. In addition, it increased serum adiponectin concentration, as well as downregulated the expression of angiotensin-converting enzyme and angiotensin II type 1A receptor genes in the heart of DS/obese rats. Our results thus show that CR attenuated obesity and hypertension, as well as left ventricular remodeling and diastolic dysfunction in DS/obese rats, with these latter effects being associated with reduced cardiac oxidative stress and inflammation.

Childhood obesity in America.

PubMed

Van Grouw, Jacqueline M; Volpe, Stella L

2013-10-01

To provide an overview of the current advances in childhood obesity physiology, intervention, and prevention. Structural and functional brain impairments are present in obese adolescents with metabolic syndrome (MetS). Aerobic training for 20 or 40 min per day produced similar affects on metabolic risk factors. Vitamin D supplementation has been shown to improve the metabolic risk factors in obese children; however, obese children require greater doses to treat vitamin D deficiency. A 10-week community-based exergaming weight management program significantly decreased the BMI in obese children. There is surmounting research on MetS and its associated risk factors in obese children. Gaining a comprehensive overview of the factors associated with obesity in children is crucial in developing the most effective intervention strategies. Community-based and family-centered interventions have generated positive results in reducing children's BMI and improving MetS risk factors. In addition to obesity intervention efforts, ongoing prevention initiatives are imperative to reduce the prevalence of childhood obesity.

School sociodemographic characteristics and obesity in schoolchildren: does the obesity definition matter?

PubMed

Bel-Serrat, Silvia; Heinen, Mirjam M; Mehegan, John; O'Brien, Sarah; Eldin, Nazih; Murrin, Celine M; Kelleher, Cecily C

2018-03-09

Existing evidence on the role of sociodemographic variables as risk factors for overweight and obesity in school-aged children is inconsistent. Furthermore, findings seem to be influenced by the obesity definition applied. Therefore, this study aimed to investigate if school sociodemographic indicators were associated with weight status in Irish primary schoolchildren and whether this association was sensitive to different obesity classification systems. A nationally representative cross-sectional sample of 7542 Irish children (53.9% girls), mean age 10.4 (±1.2SD) years, participating in the Childhood Obesity Surveillance Initiative in the 2010, 2012/2013 or 2015/2016 waves were included. Height, weight and waist circumference were objectively measured. Five definitions of obesity were employed using different approaches for either body mass index (BMI) or abdominal obesity. Associations between overweight and obesity and sociodemographic variables were investigated using adjusted multilevel logistic regression analyses. Children attending disadvantaged schools were more likely to be overweight and obese than their peers attending non-disadvantaged schools, regardless of the obesity classification system used. Associations remained significant for the BMI-based obesity definitions when the sample was stratified by sex and age group, except for boys aged 8-10.5 years. Only boys aged ≥10.5 years in disadvantaged schools had higher odds of abdominal obesity (UK 1990 waist circumference growth charts: OR = 1.56, 95%CI = 1.09-2.24; waist-to-height ratio: OR = 1.78, 95%CI = 1.14-2.79) than those in non-disadvantaged schools. No associations were observed for school urbanisation level. School socioeconomic status was a strong determinant of overweight and obesity in Irish schoolchildren, and these associations were age- and sex-dependent. School location was not associated with overweight or obesity. There remains a need to intervene with school

Linking obesity and asthma.

PubMed

Sutherland, E Rand

2014-04-01

A growing body of literature suggests that obesity has a significant impact on asthma risk, phenotype, and prognosis. Epidemiological studies have clearly demonstrated that asthma is more likely to occur in obese patients, and health status is impaired in obese individuals with asthma, with obese asthmatics experiencing more symptoms, worse quality of life, increased healthcare use, and increased asthma severity. However, obesity has well-described effects on lung function and mechanics that can lead to symptoms of dyspnea without causing the pathophysiologic changes of asthma. Adding to the challenges of evaluating this association, some studies have failed to demonstrate a robust relationship between obesity and traditional biomarkers of airway inflammation in adult asthmatics, leading to the conclusion that obesity does not necessarily worsen airway inflammation in asthma. In this regard, emerging data suggest that nonatopic mechanisms may be relevant in obese asthmatics, and that these mechanisms may have a direct impact on the response of obese asthmatics to asthma therapies, most notably inhaled glucocorticoids. This article will review selected aspects of the contributions of obesity-related airway and systemic inflammation to asthma, with a focus on the impact of obesity as a modifier of risk, prognosis, and therapeutic response in asthma. © 2014 New York Academy of Sciences.

Risk of child obesity from parental obesity: analysis of repeat national cross-sectional surveys.

PubMed

McLoone, Philip; Morrison, David S

2014-04-01

To estimate the potential to reduce childhood obesity through targeted interventions of overweight households. Cross-sectional nationally representative samples of the Scottish population. Households in Scotland during 2008 and 2009. A total of 1651 households with parents and children aged 2-15 years. The WHO cut-off points for adult body mass index (BMI): overweight (25 to <30 kg/m2) and obese (≥30 kg/m2). Overweight and obesity in childhood respectively defined as a BMI 85th to <95th percentile and ≥95th percentile based on 1990 reference centiles. Thirty-two percent (600/1849) of children and 75% (966/1290) of adults were overweight or obese. Seventy-five percent (1606/2128) of all children lived with a parent who was overweight or obese. Among obese children, 58% (185/318) lived with an obese parent. The population attributable risk percentage of child obesity associated with parental obesity was 32.5%. Targeting obese households would require substantial falls in adult weight and need to reach 38% of all children; it might achieve a reduction in the prevalence of childhood obesity of 14% in these households (from 26% to 12%). Targeting parents with BMI ≥ 40 might reduce the overall prevalence of child obesity by 9%. Such an intervention would require large weight loss, consistent with approaches used for morbidly obese adults; it would involve 4% of all children and lead to a reduction in the prevalence of obesity in these households from 57% to 16%. Family-based interventions for obesity would be most efficiently targeted at obese children whose parents are morbidly obese.

[Childhood obesity].

PubMed

Chueca, M; Azcona, C; Oyárzabal, M

2002-01-01

Obesity during childhood and adolescence is an increasingly frequent cause for medical consultation. The increase in the prevalence of this disease, which has been considered as an epidemic by the World Health Organisation, is worrying. Obesity is a complex disease, whose aetiology still remains to be clarified due to the numerous factors involved: environmental, genetic, life style and behavioural, neuroendocrinological and metabolic. The persistence of childhood obesity until adulthood significantly increases the risk of suffering from diabetes mellitus, cardiovascular disease, hypertension, cholecystitis and cholelithiasis. Treatment of obesity is complicated and few patients regularly attend follow up examinations. A multidisciplinary team is required to carry out a suitable treatment, composed of paediatricians, dieticians, nurses, psychologists and psychiatrists. Successful treatment of obesity resides in reducing the calorie intake in relation to energy expenditure, and at the time providing instruction in appropriate eating habits and life styles that in the long term will promote the maintenance of the ideal weight.

Dyslipidemia: Obese or Not Obese-That Is Not the Question.

PubMed

Ipsen, David H; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

2016-12-01

Purpose of review: It is becoming increasingly clear that some obese individuals do not develop dyslipidemia and instead remain healthy, while some normal weight individuals become dyslipidemic and unhealthy. The present review examines the similarities and differences between healthy and unhealthy individuals with and without obesity and discusses putative underlying mechanisms of dyslipidemia. The presence of dyslipidemia and compromised metabolic health in both lean and obese individuals suggests that the obese phenotype per se does not represent a main independent risk factor for the development of dyslipidemia and that dyslipidemia, rather than obesity, may be the driver of metabolic diseases. Notably, adipose tissue dysfunction and ectopic lipid deposition, in particular in the liver, seems a common trait of unhealthy individuals.

[Obesity and heart].

PubMed

Svačina, Štěpán

2014-12-01

Cardiovascular complications of obesity are traditionally considered an important complication of obesity. Obesity itself is probably not direct cause of atherosclerosis or coronary heart disease. This may occur indirectly in metabolic complications of obesity, especially diabetes and metabolic syndrome. However, thrombogenicity potential of obesity contributes to embolism and atherosclerosis development. In cardiology is well-known a phenomenon of obesity paradox when obese patients have better prognosis than thin. This is the case of heart failure and some other cardiovascular diseases. Recently, a new concept has emerged of myokines - hormones from muscle tissue that have extensive protective effects on organism and probably on heart. Whether heart is a source of myokines is uncertain. However, undoubted importance has epicardial and pericardial fatty tissue. The epicardial fatty tissue has mainly protective effects on myocardium. This fatty tissue may produce factors of inflammation affecting the myocardium. Relationship between amount of epicardial fatty tissue and coronary heart disease is rather pathogenic. Currently, it is certain that obesity brings more metabolic and cancer complications than cardiovascular and accurate contribution to pathogenic or protective character of fatty tissue in cardiology requires further research. Nevertheless, the conclusion is that adipose tissue of organism and around the heart may be in some circumstances beneficial.

Obesity drug therapy.

PubMed

Baretić, M

2013-09-01

Obesity is a chronic disease, and it requires chronic therapy. Hypertension, dyslipidemia, diabetes and cardiovascular diseases are leading causes of mortality in the modern world. All of them are strongly linked to obesity. While treating obesity, those conditions are also managed. Obese patients should always be treated through lifestyle interventions, though the results of such interventions are modest. Pharmacotherapy is a second step in the treatment of obesity, approved only when weight loss targets were not reached through lifestyle intervention. During the history of antiobesity drugs, many of them were withdrawn because of their side effects. Various guidelines recommend prescribing drug therapy for obesity through consideration of the potential benefits and limitations. Orlistat deactivates intestinal lipase and inhibits intestinal fat lipolysis. It is actually the only drug on the European market approved for the treatment of obesity. Orlistat therapy reduces weight to a modest extent, but it reduces the incidence of diabetes beyond the result achieved with lifestyle changes. Recently, some effective antiobesity drugs like sibutramine and rimonabant have been removed from the market due to their side effects. The new combination of topimarate and fentermine is approved in the US but not in Europe. The cost effectiveness of long-term pharmacotherapy of obesity is still an unresolved question.

Obesity Metaphors: How Beliefs about the Causes of Obesity Affect Support for Public Policy

PubMed Central

Barry, Colleen L; Brescoll, Victoria L; Brownell, Kelly D; Schlesinger, Mark

2009-01-01

Context: Relatively little is known about the factors shaping public attitudes toward obesity as a policy concern. This study examines whether individuals' beliefs about the causes of obesity affect their support for policies aimed at stemming obesity rates. This article identifies a unique role of metaphor-based beliefs, as distinct from conventional political attitudes, in explaining support for obesity policies. Methods: This article used the Yale Rudd Center Public Opinion on Obesity Survey, a nationally representative web sample surveyed from the Knowledge Networks panel in 2006/07 (N = 1,009). The study examines how respondents' demographic and health characteristics, political attitudes, and agreement with seven obesity metaphors affect support for sixteen policies to reduce obesity rates. Findings: Including obesity metaphors in regression models helps explain public support for policies to curb obesity beyond levels attributable solely to demographic, health, and political characteristics. The metaphors that people use to understand rising obesity rates are strong predictors of support for public policy, and their influence varies across different types of policy interventions. Conclusions: Over the last five years, the United States has begun to grapple with the implications of dramatically escalating rates of obesity. Individuals use metaphors to better understand increasing rates of obesity, and obesity metaphors are independent and powerful predictors of support for public policies to curb obesity. Metaphorical reasoning also offers a potential framework for using strategic issue framing to shift support for obesity policies. PMID:19298414

Obesity Epidemiology Worldwide.

PubMed

Arroyo-Johnson, Cassandra; Mincey, Krista D

2016-12-01

Obesity continues to be a public health concern across the globe. Obesity has a demonstrated association with health behaviors and health outcomes, such as diabetes, hypertension, and cancer. Over the past 2 decades, obesity has increased worldwide and remains highest in the United States. It is critical to understand the definition of obesity, using body mass index appropriately, recent estimates, and risk factors as a framework within which clinicians should work to help reduce the burden of obesity. This framework, including the Healthy People 2020 place-based approach to social determinants of health, is described in this article. Copyright © 2016 Elsevier Inc. All rights reserved.

Obesity and Heart Failure: Focus on the Obesity Paradox.

PubMed

Carbone, Salvatore; Lavie, Carl J; Arena, Ross

2017-02-01

The escalating prevalence of obesity has been linked to substantial increases in both metabolic and cardiovascular disease. Nevertheless, the direct effects of obesity on cardiovascular health and function require further exploration. In particular, the relationship between obesity and cardiac function has received intense scrutiny. Although obesity increases the risk for development of heart failure (HF), it appears to exert a protective effect in patients in whom HF has already been diagnosed (the "obesity paradox"). The protective effects of obesity in patients with previously diagnosed HF are the focus of particularly intense research. Several explanations have been proposed, but most studies are limited by the use of body mass index to classify obesity. Because body mass index does not distinguish between fat mass, fat-free mass, and lean mass, individuals with similar body mass indices may have vastly different body composition. This article discusses the roles of body composition, diet, cardiorespiratory fitness, and weight loss in the development of cardiac dysfunction and HF and the potential protective role that body composition compartments might play in improving HF prognosis. Based on an intensive literature search (Pubmed, Google Scholar) and critical review of the literature, we also discuss how a multidisciplinary approach including a nutritional intervention targeted to reduce systemic inflammation and lean mass-targeted exercise training could potentially exert beneficial effects for patients with HF. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Treadmill exercise prevents diabetes-induced increases in lipid peroxidation and decreases in Cu,Zn-superoxide dismutase levels in the hippocampus of Zucker diabetic fatty rats.

PubMed

Kim, Jong Whi; Chae, Junghyun; Nam, Sung Min; Kim, Yo Na; Yoo, Dae Young; Choi, Jung Hoon; Jung, Hyo Young; Song, Wook; Hwang, In Koo; Seong, Je Kyung; Yoon, Yeo Sung

2015-01-01

In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.

Differences in taste sensitivity between obese and non-obese children and adolescents.

PubMed

Overberg, Johanna; Hummel, Thomas; Krude, Heiko; Wiegand, Susanna

2012-12-01

Taste sensitivity varies between individuals. Several studies describe differences between obese and non-obese subjects concerning their taste perception. However, data are partly contradictory and insufficient. Therefore, in this study taste sensitivity of obese and non-obese children/adolescents was analysed. In a cross-sectional study gustatory sensitivity of n=99 obese subjects (body mass index (BMI) >97th percentile) and n=94 normal weight subjects (BMI <90th percentile), 6-18 years of age, was compared. Sensitivity for the taste qualities sweet, sour, salty, umami and bitter was analysed by means of impregnated 'taste strips' in different concentrations. A total score was determined for all taste qualities combined as well as for each separately. Furthermore, the possible influence of sex, age and ethnicity on taste perception was analysed. An intensity rating for sweet was performed on a 5-point rating scale. Obese subjects showed-compared to the control group-a significantly lower ability to identify the correct taste qualities regarding the total score (p<0.001). Regarding individual taste qualities there was a significantly lower detection rate for salty, umami and bitter by obese subjects. Furthermore, the determinants age and sex had a significant influence on taste perception: older age and female sex was associated with better ability to identify taste qualities. Concerning the sweet intensity rating obese children gave significantly lower intensity ratings to three of the four concentrations. Obese and non-obese children and adolescents differ in their taste perception. Obese subjects could identify taste qualities less precisely than children and adolescents of normal weight.

Occupation-specific absenteeism costs associated with obesity and morbid obesity.

PubMed

Cawley, John; Rizzo, John A; Haas, Kara

2007-12-01

To document the absenteeism costs associated with obesity and morbid obesity by occupation. Data from the Medical Expenditure Panel Survey for 2000-2004 are examined. The outcomes are probability of missing any work in the previous year and number of days of work missed in the previous year. Predictors include clinical weight classification, age, education, and race. Models are estimated separately by gender and occupation category. The probability of missing work in the past year, number of days missed, and costs of absenteeism rise with clinical weight classification for both women and men, and vary across occupation. Absenteeism costs associated with obesity total $4.3 billion annually in the United States. Substantial absenteeism costs are associated with obesity and morbid obesity. Employers should explore workplace interventions and health insurance expansions to reduce these costs.

Ibipinabant attenuates β-cell loss in male Zucker diabetic fatty rats independently of its effects on body weight.

PubMed

Rohrbach, K; Thomas, M A; Glick, S; Fung, E N; Wang, V; Watson, L; Gregory, P; Antel, J; Pelleymounter, M A

2012-06-01

To test the antidiabetic efficacy of ibipinabant, this new cannabinoid receptor 1 (CB1) antagonist was compared with food-restriction-induced weight loss, rosiglitazone (4 mg/kg) and rimonabant (3 and 10 mg/kg), using parameters of glycaemic control in male Zucker diabetic fatty (ZDF) rats. Body weight, food and water intake, fasted and non-fasted glucose and insulin, glucose tolerance and glycosylated haemoglobin (HbA1c) were all assessed over the course of the 9-week study. Pancreatic insulin content and islet area were also evaluated. At the end of the study, vehicle-treated ZDF rats were severely hyperglycaemic and showed signs of β-cell decline, including dramatic reductions in unfasted insulin levels. Ibipinanbant (10 mg/kg) reduced the following relative to vehicle controls: fasting glucose (-61%), glucose excursion area under the curve (AUC) in an oral glucose tolerance test (OGTT, -44%) and HbA1c (-50%). Furthermore, non-fasting insulin, islet area and islet insulin content were all increased (71, 40 and 76%, respectively) relative to vehicle controls by the end of the study. All of these effects were similar to those of rimonabant and rosiglitazone, where ibipinabant was slightly more effective than rimonabant at the lowest dose and somewhat less effective than rosiglitazone at all doses. These antidiabetic effects appear independent of weight loss because none of the parameters above were consistently improved by the comparable weight loss induced by food restriction. Ibipinabant may have weight loss-independent antidiabetic effects and may have the potential to attenuate β-cell loss in a model of progressive β-cell dysfunction. © 2012 Blackwell Publishing Ltd.

The fast food and obesity link: consumption patterns and severity of obesity.

PubMed

Garcia, Ginny; Sunil, Thankam S; Hinojosa, Pedro

2012-05-01

Rates of extreme forms of obesity are rapidly rising, as is the use of bariatric surgery for its treatment. The aim of the present study was to examine selected behavioral factors associated with severity of obesity among preoperative bariatric surgery patients in the San Antonio area, focusing specifically on the effects of fast food consumption. We used ordered logistic regression to model behavioral and attitudinal effects on obesity outcomes among 270 patients. These outcomes were based on the severity of obesity and were measured on the basis of body mass index. Our results indicated that, among the behavioral factors, fast food consumption exerted the largest influence on higher levels of obesity. These remained after controlling for several social and demographic characteristics. Our findings suggest that higher rates of fast food consumption are connected to the increasing rates of severe obesity. Given that morbid and super morbid obesity rates are growing at a more advanced pace than moderate obesity, it is necessary to explore the behavioral characteristics associated with these trends.

Psychological aspects of obesity.

PubMed

Fabricatore, Anthony N; Wadden, Thomas A

2004-01-01

Obesity is a complex condition associated with a host of medical disorders. A common assumption is that obesity must also be related to psychological and emotional complications. Research on the psychosocial aspects of obesity has grown more sophisticated over the years, from purely theoretical papers to cross-sectional comparisons of people with and without obesity to prospective investigations of the temporal sequence of obesity and mood disturbance. These studies have shown that obesity, by itself, does not appear to be systematically associated with psychopathological outcomes. Certain obese individuals, however, are at greater risk of psychiatric disorder, especially depression. The present paper reviews the research findings and presents their clinical implications. Chiefly, treatment providers should not assume that a depressed or otherwise disturbed obese person needs only to lose weight in order to return to psychological health. Significant mood disturbances should be treated equally aggressively, regardless of a patient's weight status.

Obesity: Pathophysiology and Intervention

PubMed Central

Zhang, Yi; Liu, Ju; Yao, Jianliang; Ji, Gang; Qian, Long; Wang, Jing; Zhang, Guansheng; Tian, Jie; Nie, Yongzhan; Zhang, Yi Edi.; Gold, Mark S.; Liu, Yijun

2014-01-01

Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity. PMID:25412152

[Epigenetics and obesity].

PubMed

Casanello, Paola; Krause, Bernardo J; Castro-Rodríguez, José A; Uauy, Ricardo

Current evidence supports the notion that exposure to various environmental conditions in early life may induce permanent changes in the epigenome that persist throughout the life-course. This article focuses on early changes associated with obesity in adult life. A review is presented on the factors that induce changes in whole genome (DNA) methylation in early life that are associated with adult onset obesity and related disorders. In contrast, reversal of epigenetic changes associated with weight loss in obese subjects has not been demonstrated. This contrasts with well-established associations found between obesity related DNA methylation patterns at birth and adult onset obesity and diabetes. Epigenetic markers may serve to screen indivuals at risk for obesity and assess the effects of interventions in early life that may delay or prevent obesity in early life. This might contribute to lower the obesity-related burden of death and disability at the population level. The available evidence indicates that epigenetic marks are in fact modifiable, based on modifications in the intrauterine environment and changes in food intake, physical activity and dietary patterns patterns during pregnancy and early years of adult life. This offers the opportunity to intervene before conception, during pregnancy, infancy, childhood, and also in later life. There must be documentation on the best preventive actions in terms of diet and physical activity that will modify or revert the adverse epigenetic markers, thus preventing obesity and diabetes in suceptible individuals and populations. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

[Obesity in Mexico].

PubMed

Dávila-Torres, Javier; González-Izquierdo, José Jesús; Barrera-Cruz, Antonio

2015-01-01

Excess body weight (overweight and obesity) is currently recognized as one of the most important challenges of public health in the world, given its size, speed of growth and the negative effect it has on the health of the population that suffers. Overweight and obesity significantly increases the risk of chronic no communicable diseases, premature mortality and the social cost of health. An estimated 90 % of cases of type 2 diabetes mellitus attributable to overweight and obesity. Today, Mexico is second global prevalence of obesity in the adult population, which is ten times higher than that of countries like Japan and Korea. With regard to children, Mexico ranks fourth worldwide obesity prevalence, behind Greece, USA and Italy. In our country, over 70 % of the adult population, between 30 and 60 years are overweight. The prevalence of overweight is higher in men than females, while the prevalence of obesity is higher in women than men. Until 2012, 26 million Mexican adults are overweight and 22 million obese, which represents a major challenge for the health sector in terms of promoting healthy lifestyles in the population and development of public policies to reverse this scenario epidemiology. Mexico needs to plan and implement strategies and action cost effective for the prevention and control of obesity of children, adolescents and adults. Global experience shows that proper care of obesity and overweight, required to formulate and coordinate multisectoral strategies and efficient for enhancing protective factors to health, particularly to modify individual behavior, family and community.

Macrophage migration inhibitory factor in obese and non obese women with polycystic ovary syndrome.

PubMed

Mejia-Montilla, Jorly; Álvarez-Mon, Melchor; Reyna-Villasmil, Eduardo; Torres-Cepeda, Duly; Santos-Bolívar, Joel; Reyna-Villasmil, Nadia; Suarez-Torres, Ismael; Bravo-Henríquez, Alfonso

2015-01-01

To measure macrophage migration inhibitory factor (MIF) concentrations in obese and non-obese women diagnosed with polycystic ovary syndrome (PCOS). Women diagnosed with PCOS and age-matched healthy controls with regular menses and normal ovaries on ultrasound examination were selected and divided into 4 groups (group A, PCOS and obese; group B, PCOS and non-obese; group C, obese controls; and group D, non-obese controls) based on body mass index (obese >30 kg/m2 and non-obese <25 kg/m2). Luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, sex hormone-binding globulin, serum glucose, insulin and MIF levels were measured. Obese and non-obese women with PCOS had higher luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, and insulin levels as compared to the obese and non-obese control groups, respectively (P < .0001). Women with PCOS had significantly higher MIF levels (group A, 48.6 ± 9.9 mg/ml; group B, 35.2 ± 6.0 ng/ml) as compared to controls (group C, 13.5 ± 6.0 ng/ml; group D, 12.0 ± 4.3 ng/dl; P < .0001). A weak, positive and significant correlation was seen between fasting blood glucose and insulin levels in women with PCOS (P < .05). Significant differences exist in plasma MIF levels between obese and non-obese women with and without PCOS. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

Redrawing the US Obesity Landscape: Bias-Corrected Estimates of State-Specific Adult Obesity Prevalence

PubMed Central

Ward, Zachary J.; Long, Michael W.; Resch, Stephen C.; Gortmaker, Steven L.; Cradock, Angie L.; Giles, Catherine; Hsiao, Amber; Wang, Y. Claire

2016-01-01

Background State-level estimates from the Centers for Disease Control and Prevention (CDC) underestimate the obesity epidemic because they use self-reported height and weight. We describe a novel bias-correction method and produce corrected state-level estimates of obesity and severe obesity. Methods Using non-parametric statistical matching, we adjusted self-reported data from the Behavioral Risk Factor Surveillance System (BRFSS) 2013 (n = 386,795) using measured data from the National Health and Nutrition Examination Survey (NHANES) (n = 16,924). We validated our national estimates against NHANES and estimated bias-corrected state-specific prevalence of obesity (BMI≥30) and severe obesity (BMI≥35). We compared these results with previous adjustment methods. Results Compared to NHANES, self-reported BRFSS data underestimated national prevalence of obesity by 16% (28.67% vs 34.01%), and severe obesity by 23% (11.03% vs 14.26%). Our method was not significantly different from NHANES for obesity or severe obesity, while previous methods underestimated both. Only four states had a corrected obesity prevalence below 30%, with four exceeding 40%–in contrast, most states were below 30% in CDC maps. Conclusions Twelve million adults with obesity (including 6.7 million with severe obesity) were misclassified by CDC state-level estimates. Previous bias-correction methods also resulted in underestimates. Accurate state-level estimates are necessary to plan for resources to address the obesity epidemic. PMID:26954566

Parental overweight/obesity, social factors, and child overweight/obesity at 7 years of age.

PubMed

Xu, Li; Dubois, Lise; Burnier, Daniel; Girard, Manon; Prud'homme, Denis

2011-12-01

This study used gender-based analyses to examine whether child overweight/obesity is related to parental overweight/obesity and sociodemographic factors, in a representative population-based cohort of 7-year-old children. Data from the Québec Longitudinal Study of Child Development 1998-2010 was used. Children (n= 1336) were randomly selected from each public health region of Québec. The study was based on face-to-face interviews and a set of questionnaires addressed to mothers and fathers. Compared to children with no overweight/obese parent, the adjusted odds ratio (OR) of being overweight/obese with two overweight/obese parents was 5 for boys (95% confidence interval [CI]: 2.31-10.85) and 5.87 for girls (95%CI: 2.63-13.12). Gender differences appeared when one parent was overweight/obese. For girls, having either an overweight/obese mother (OR, 3.10; 95%CI: 1.14-8.38) or father (OR, 3.64; 95%CI: 1.68-7.91) significantly increased the odds of being overweight/obese at 7 years. For boys, however, having only an overweight/obese father (OR, 2.05; 95%CI: 1.01-4.16) was related to overweight/obesity, but having only an overweight/obese mother was not related to overweight/obesity at 7 years for boys. In girls, but not in boys, having an immigrant mother also significantly related to overweight/obesity (OR, 2.71; 95%CI: 1.28-5.75) at 7 years, after controlling for other social factors. Gender differences in socialization may explain why at 7 years of age, girls' bodyweight is influenced by having even one overweight/obese parent (mother or father), while boys' bodyweight appears to be influenced only by father's overweight/obesity when only one parent is overweight/obese. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Relationship between visceral obesity and plasma fibrinogen in obese children.

PubMed

Hafez, Mona; El-Masry, Sahar; Musa, Noha; Fathy, Marwa; Hassan, Mona; Hassan, Nayera; El Husseiny, Mohamed; Tareef, Mahmoud

2016-03-01

The prevalence of obesity in children and adolescents has increased significantly worldwide with an alarming rise of its co-morbidities. The excess of visceral adipose tissue is associated with hypertension, prothrombotic and pro-inflammatory states. Our aim was to find a possible association between visceral obesity and plasma fibrinogen, as one of the cardiovascular risk factors, in obese children. Forty-three obese children and 40 non-obese controls were studied regarding their history, complete physical examination, anthropometric assessment, body composition analysis, ultrasonographic measurement of visceral adipose tissue and subcutaneous fat as well as laboratory measurement of plasma fibrinogen. Our study revealed significant higher levels of fibrinogen in obese children than controls (14.5+5.1 and 2.9+0.52 mg/mL, respectively) with p-value <0.01. Moreover, the obese group had statistically significant difference in visceral fat (5.96+0.77 cm) and subcutaneous fat (2.66+0.70 cm) than controls (2.45+0.65 and 0.70+0.18 mg/mL, respectively) with p-value <0.01. In addition, fibrinogen had significant positive correlation with body mass index (r=0.327), waist/hip ratio (r=0.394), fat percentage (r=0.301), visceral adipose tissue (r=0.323) and subcutaneous fat (r=0.301). There was highly significant increase in the fibrinogen level, visceral and subcutaneous abdominal fat in the obese group with insignificant sex differences. Fibrinogen had a significant positive correlation with the different adiposity markers, blood pressure, visceral and subcutaneous fat. Visceral adipose tissue is a stronger predictor for cardiovascular risk compared to subcutaneous fat.

Challenges in obesity research.

PubMed

Palou, Andreu; Bonet, M Luisa

2013-09-01

Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Polygenic obesity in humans.

PubMed

Hinney, Anke; Hebebrand, Johannes

2008-01-01

The molecular genetic analysis of obesity has led to the identification of a limited number of confirmed major genes. While such major genes have a clear influence on the development of the phenotype, the underlying mutations are however (extremely) infrequent and thus of minor clinical importance only. The genetic predisposition to obesity must thus be polygenic; a number of such variants should be found in most obese subjects; however, these variants predisposing to obesity are also found in normal weight and even lean individuals. Therefore, a polygene can only be identified and validated by statistical analyses: the appropriate gene variant (allele) occurs more frequently in obese than in non-obese subjects. Each single polygene makes only a small contribution to the development of obesity. The 103Ile allele of the Val103Ile single nucleotide polymorphism (SNP) of the melanocortin-4 receptor gene (MC4R) was the first confirmed polygenetic variant with an influence on the body mass index (BMI); the more common Val103 allele is more frequent in obese individuals. As determined in a recent, large-scaled meta-analysis the effect size of this allele on mean BMI was approximately -0.5 kg/m(2). The first genome-wide association study (GWA) for obesity, based on approximately 100,000 SNPs analyzed in families of the Framingham study, revealed that a SNP in the proximity of the insulin-induced gene 2 (INSIG2) was associated with obesity. The positive result was replicated in independent samples; however, some other study groups detected no association. Currently, a meta-analysis is ongoing; its result will contribute to the evaluation of the importance of the INSIG2 polymorphism in body weight regulation. SNP alleles in intron 1 of the fat mass and obesity associated gene (FTO) confer the most relevant polygenic effect on obesity. In the first GWA for extreme early onset obesity we substantiated that variation in FTO strongly contributes to early onset obesity

Endoscopic Devices for Obesity.

PubMed

Sampath, Kartik; Dinani, Amreen M; Rothstein, Richard I

2016-06-01

The obesity epidemic, recognized by the World Health Organization in 1997, refers to the rising incidence of obesity worldwide. Lifestyle modification and pharmacotherapy are often ineffective long-term solutions; bariatric surgery remains the gold standard for long-term obesity weight loss. Despite the reported benefits, it has been estimated that only 1% of obese patients will undergo surgery. Endoscopic treatment for obesity represents a potential cost-effective, accessible, minimally invasive procedure that can function as a bridge or alternative intervention to bariatric surgery. We review the current endoscopic bariatric devices including space occupying devices, endoscopic gastroplasty, aspiration technology, post-bariatric surgery endoscopic revision, and obesity-related NOTES procedures. Given the diverse devices already FDA approved and in development, we discuss the future directions of endoscopic therapies for obesity.

Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat.

PubMed

Gheni, Ghupurjan; Yokoi, Norihide; Beppu, Masayuki; Yamaguchi, Takuro; Hidaka, Shihomi; Kawabata, Ayako; Hoshino, Yoshikazu; Hoshino, Masayuki; Seino, Susumu

2015-01-01

We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6-8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10-12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain.

Obesity: modern man's fertility nemesis.

PubMed

Cabler, Stephanie; Agarwal, Ashok; Flint, Margot; du Plessis, Stefan S

2010-07-01

The obesity pandemic has grown to concerning proportions in recent years, not only in the Western World, but in developing countries as well. The corresponding decrease in male fertility and fecundity may be explained in parallel to obesity, and obesity should be considered as an etiology of male fertility. Studies show that obesity contributes to infertility by reducing semen quality, changing sperm proteomes, contributing to erectile dysfunction, and inducing other physical problems related to obesity. Mechanisms for explaining the effect of obesity on male infertility include abnormal reproductive hormone levels, an increased release of adipose-derived hormones and adipokines associated with obesity, and other physical problems including sleep apnea and increased scrotal temperatures. Recently, genetic factors and markers for an obesity-related infertility have been discovered and may explain the difference between fertile obese and infertile obese men. Treatments are available for not only infertility related to obesity, but also as a treatment for the other comorbidities arising from obesity. Natural weight loss, as well as bariatric surgery are options for obese patients and have shown promising results in restoring fertility and normal hormonal profiles. Therapeutic interventions including aromatase inhibitors, exogenous testosterone replacement therapy and maintenance and regulation of adipose-derived hormones, particularly leptin, may also be able to restore fertility in obese males. Because of the relative unawareness and lack of research in this area, controlled studies should be undertaken and more focus should be given to obesity as an etiolgy of male infertility.

Neurological Consequences of Obesity

PubMed Central

O’Brien, Phillipe D.; Hinder, Lucy M.; Callaghan, Brian C.; Feldman, Eva L.

2017-01-01

Obesity, primarily a consequence of poor dietary choices and an increased sedentary lifestyle, has become a global pandemic that brings with it enormous medical, social, and economic challenges. Not only does obesity increase the risk of cardiovascular disease and certain cancers, but it is also recognized as a key driver of other metabolic syndrome (MetS) components. These components include insulin resistance, hyperglycemia with prediabetes or type 2 diabetes, dyslipidemia, and hypertension, and are underlying contributors to systemic metabolic dysfunction. More recently, obesity and diet-induced metabolic dysfunction have been identified as risk factors for the development of a wide variety of neurological disorders in both the central and peripheral nervous systems. An abundance of literature has shown that obesity is associated with mild cognitive impairment and altered hippocampal structure and function, and there is a robust correlation between obesity and Alzheimer’s type dementia. Similarly, many reports show that both the autonomic and somatic components of the peripheral nervous system are impacted by obesity. The autonomic nervous system, under control of the hypothalamus, displays altered catabolic and anabolic processes in obese individuals attributed to sympathetic-parasympathetic imbalances. A close association also exists between obesity and polyneuropathy, a complication most commonly found in prediabetic and diabetic patients, and is likely secondary to a combination of obesity-induced dyslipidemia with hyperglycemia. This review will outline the pathophysiological development of obesity and dyslipidemia, discuss the adverse impact of these conditions on the nervous system, and provide evidence for lipotoxicity and metabolic inflammation as the drivers underlying the neurological consequences of obesity. In addition, this review will examine the benefits of lifestyle and surgical interventions in obesity-induced neurological disorders. PMID

[The personality of obese persons in psychological tests with special consideration on latent obesity].

PubMed

Pudel, V; Metzdorff, M; Oetting, M

1975-01-01

The results of psychological tests of the obese are inconsistent and no characteristic personality structure of the obese can be deduced from them. Investigations in childhood obesity failed to establish a general psychogenetic model of obesity. Yet overweight and ideal weight-subjects differ in spontaneous eating behaviour. Appetite and satiety of obese subjects are controlled by external stimuli to a far greater extent than in nonobese. From a behavioural scientific viewpoint it is proposed that learning experiences during childhood socialisation generate the disposition for obesity which can manifest itself later, after interaction with a special environment. At this stage, however, individual reactions to starting overweight are insolved; this process is strongly influenced by individual personality structures: an inadequate conflict management favours obesity; by cognitive control normal weight can be preserved in spite of the acquired disposition for obesity. Taking these "latently obese" as an example the role of personality structure and wrong eating habits is discussed and related to possible therapeutic strategies. A model of the psychogenetic basis of obesity is proposed. In this model eating-related learning experience is attributed a primary role and individual personality structure a secondary role in the psychogenesis of obesity.

Obesity, Inflammation, and Cancer.

PubMed

Deng, Tuo; Lyon, Christopher J; Bergin, Stephen; Caligiuri, Michael A; Hsueh, Willa A

2016-05-23

Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity.

Prepregnancy obesity and pregnancy outcome.

PubMed

Ahmed, Salah R; Ellah, Mostafa A A; Mohamed, Osman A; Eid, Hesham M

2009-07-01

Maternal obesity has long been correlated with an increased risk of chronic hypertension and diabetes prior to pregnancy and adverse pregnancy outcomes including preeclampsia, gestational diabetes, fetal macrosomia, Cesarean deliveries, postpartum endometritis and a prolonged hospital stay To determine the effect of maternal pre-pregnancy obesity on pregnancy outcomes Methods: One hundred and twenty two women were recruited in the study. The patients were allocated into two groups, group 1 obese patients (68) BMI 30 or more and group 2 non obese patients (54) BMI between 19.8-24.9. About two - third of the study group were having mild obesity, moderate obesity comprised about 28% and about 4% only was morbidly obese. Hypertensive disorders were nine folds more among obese women (R.R 4.74). Obese pregnant women were significantly more prone to have gestational diabetes (R.R 6.35). Even anemia was significantly more amongst Obese women when compared to non obese ones (29/68, R.R 3.84). Ante partum hemorrhage had significantly more in obese women (R.R 3.14). There was no increased risk for PROM (R.R 0.71). Moreover The macrosomic babies were extremely commoner among obese (R.R 9.1). Pre-pregnancy obesity is a risk factor for gestational diabetes, preeclampsia, labor induction, cesarean section for fetal distress, and wound infection. They should be considered as high risk and counseled accordingly.

[Obesity and the prognosis of heart failure: the obesity paradox, myth or reality?].

PubMed

Bounhoure, Jean-Paul; Galinier, Michel; Roncalli, Jerôme; Massabuau, Pierre

2014-01-01

Obesity has now reached epidemic proportions worldwide. Obesity is associated with numerous comorbidities, including hypertension, lipid disorders and type II diabetes, and is also a major cause of cardiovascular disease, coronary disease, heart failure, atrial fibrillation, and sudden death. Obesity is the main cause of heart failure in respectively 11% and 14% of cases in men and women. The Framingham study showed that, after correction for other risk factors, each point increase in the body mass index raises the risk of heart failure by 5% in men and 7% in women. Obesity increases the heart workload, causes left ventricular hypertrophy, and impairs both diastolic and systolic function. The most common form of heart failure is diastolic dysfunction, and heart failure in obese individuals is associated with preserved systolic function. Despite these comorbidities and the severity of heart failure, numerous studies have revealed an "obesity paradox" in which overweight and obese individuals with heart failure appear to have a better prognosis than non overweight subjects. This review summarizes the adverse cardiac effects of this nutritional disease, the results of some studies supporting the obesity paradox, the better survival rate of obese patients with heart failure. Potential explanations for these surprising data include the possibility that a number of obese patients may simply not have heart failure, as well as methodological bias, and protective effects of adipose tissue. Further studies of large populations are needed to determine how obesity may improve the prognosis of heart failure.

Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox.

PubMed

Lavie, Carl J; McAuley, Paul A; Church, Timothy S; Milani, Richard V; Blair, Steven N

2014-04-15

Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Genetics of pediatric obesity.

PubMed

Manco, Melania; Dallapiccola, Bruno

2012-07-01

Onset of obesity has been anticipated at earlier ages, and prevalence has dramatically increased worldwide over the past decades. Epidemic obesity is mainly attributable to modern lifestyle, but family studies prove the significant role of genes in the individual's predisposition to obesity. Advances in genotyping technologies have raised great hope and expectations that genetic testing will pave the way to personalized medicine and that complex traits such as obesity will be prevented even before birth. In the presence of the pressing offer of direct-to-consumer genetic testing services from private companies to estimate the individual's risk for complex phenotypes including obesity, the present review offers pediatricians an update of the state of the art on genomics obesity in childhood. Discrepancies with respect to genomics of adult obesity are discussed. After an appraisal of findings from genome-wide association studies in pediatric populations, the rare variant-common disease hypothesis, the theoretical soil for next-generation sequencing techniques, is discussed as opposite to the common disease-common variant hypothesis. Next-generation sequencing techniques are expected to fill the gap of "missing heritability" of obesity, identifying rare variants associated with the trait and clarifying the role of epigenetics in its heritability. Pediatric obesity emerges as a complex phenotype, modulated by unique gene-environment interactions that occur in periods of life and are "permissive" for the programming of adult obesity. With the advent of next-generation sequencing techniques and advances in the field of exposomics, sensitive and specific tools to predict the obesity risk as early as possible are the challenge for the next decade.

Obesity and Cardiovascular Disease.

PubMed

Ortega, Francisco B; Lavie, Carl J; Blair, Steven N

2016-05-27

The prevalence of obesity has increased worldwide over the past few decades. In 2013, the prevalence of obesity exceeded the 50% of the adult population in some countries from Oceania, North Africa, and Middle East. Lower but still alarmingly high prevalence was observed in North America (≈30%) and in Western Europe (≈20%). These figures are of serious concern because of the strong link between obesity and disease. In the present review, we summarize the current evidence on the relationship of obesity with cardiovascular disease (CVD), discussing how both the degree and the duration of obesity affect CVD. Although in the general population, obesity and, especially, severe obesity are consistently and strongly related with higher risk of CVD incidence and mortality, the one-size-fits-all approach should not be used with obesity. There are relevant factors largely affecting the CVD prognosis of obese individuals. In this context, we thoroughly discuss important concepts such as the fat-but-fit paradigm, the metabolically healthy but obese (MHO) phenotype and the obesity paradox in patients with CVD. About the MHO phenotype and its CVD prognosis, available data have provided mixed findings, what could be partially because of the adjustment or not for key confounders such as cardiorespiratory fitness, and to the lack of consensus on the MHO definition. In the present review, we propose a scientifically based harmonized definition of MHO, which will hopefully contribute to more comparable data in the future and a better understanding on the MHO subgroup and its CVD prognosis. © 2016 American Heart Association, Inc.

Impact of Obesity on Heart and Lung Transplantation: Does Pre-Transplant Obesity Affect Outcomes?

PubMed

Bozso, S J; Nagendran, Je; Gill, R S; Freed, D H; Nagendran, Ja

2017-03-01

Increasing prevalence of obesity has led to a rise in the number of prospective obese heart and lung transplant recipients. The optimal management strategy of obese patients with end-stage heart and lung failure remains controversial. This review article discusses and provides a summary of the literature surrounding the impact of obesity on outcomes in heart and lung transplantation. Studies on transplant obesity demonstrate controversy in terms of morbidity and mortality outcomes and obesity pre-transplantation. However, the impact of obesity on outcomes seems to be more consistently demonstrated in lung rather than heart transplantation. The ultimate goal in heart and lung transplantation in the obese patient is to identify those at highest risk of complication that may warrant therapies to mitigate risk by addressing comorbid conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of circulating adipokines with metabolic dyslipidemia in obese versus non-obese individuals.

PubMed

Rahimlou, Mehran; Mirzaei, Khadijeh; Keshavarz, Seyed Ali; Hossein-Nezhad, Arash

2016-01-01

Previous studies have shown that circulating adipokines may play an important role in the pathogenesis of some obesity related chronic disease such as dyslipidemia and type2 diabetes mellitus. The aim of the present study was to investigate the association between vaspin, omentin-1 and retinol binding protein-4 levels with metabolic dyslipidemia (MD) criteria in obese and non-obese individuals. The study was conducted on 170 obese and 81 non-obese individuals. After collecting the blood samples, serum levels metabolic parameters as well as three circulating adipokines and body composition were measured. No significant difference was noted regarding the mean serum levels of omentin-1 and vaspin between the obese and non-obese groups, while, serum level of RBP4 was significantly higher in the non-obese group. We found the 0.22 increased risk of MD in obese individuals with higher RBP4 concentration. After the adjustment for confounding factors, this association was still significant. No significant association was noted between MD and its components relative risks with omentin-1 and vaspin levels. Our study demonstrated that circulating RBP4 was significantly higher in the obese individuals which may increase the risk of MD in them. Further researches are needed to address this association. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Obesity and Psychoanalysis.

ERIC Educational Resources Information Center

Rand, Colleen S.; Stunkard, Albert J.

This report describes a collaborative study undertaken by 72 psychoanalysts in an effort to (1) collect systematic data about obese patients in psychoanalysis and (2) assess the effect of psychoanalysis in the treatment of obesity. A total of 84 obese and 63 normal weight patients was studied. Each analyst completed a detailed questionnaire on his…

Obesity in America.

PubMed

Menifield, Charles E; Doty, Nicole; Fletcher, Audwin

2008-01-01

Recent data indicate that Americans are gaining weight at an alarming rate. In fact, data from the CDC indicate that the U.S. obesity average was 12% in 1990 and had grown to 23% by 2005. In recent years, this problem appears to be more prominent in some southern states than in other states. The purpose of this study was to determine what factors were associated with increased levels of obesity. Do demographic, educational, healthcare, or economic factors correlate with this trend? Using state level data in a fixed effects regression model we examined obesity rates for the period 1990-2003. We also used cross tabulation tables to compare obesity rates to several independent variables. Our analysis revealed that obesity was related to several health, demographic, and economic factors. As a result, we argue that policy makers as well as health officials should take a comprehensive look at obesity as well as other social ills, health care conditions, and related issues prior to creating a plan to improve health in this country.

Gastrointestinal Morbidity in Obesity

PubMed Central

Acosta, Andres; Camilleri, Michael

2014-01-01

Obesity is a complex disease that results from increased energy intake and decreased energy expenditure. The gastrointestinal system plays a key role in the pathogenesis of obesity and facilitates caloric imbalance. Changes in gastrointestinal hormones and the inhibition of mechanisms that curtail caloric intake result in weight gain. It is not clear if the gastrointestinal role in obesity is a cause or an effect of this disease. Obesity is often associated with type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Obesity is also associated with gastrointestinal disorders, which are more frequent and present earlier than T2DM and CVD. Diseases such as gastro-esophageal reflux disease, cholelithiasis or non-alcoholic steatohepatitis are directly related to body weight and abdominal adiposity. Our objective is to assess the role of each gastrointestinal organ in obesity and the gastrointestinal morbidity resulting in those organs from effects of obesity. PMID:24602085

Evidence in obese children: contribution of hyperlipidemia, obesity-inflammation, and insulin sensitivity.

PubMed

Chang, Chi-Jen; Jian, Deng-Yuan; Lin, Ming-Wei; Zhao, Jun-Zhi; Ho, Low-Tone; Juan, Chi-Chang

2015-01-01

Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, and insulin sensitivity in overweight/obese children. We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits. Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%). Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future.

Childhood obesity in specialist care--searching for a healthy obese child.

PubMed

Dalla Valle, Marketta; Laatikainen, Tiina; Kalliokoski, Tomi; Nykänen, Päivi; Jääskeläinen, Jarmo

2015-01-01

One in three obese adults is classified as metabolically healthy, but there is less evidence in obese children. We studied the overall clinical presentation of Finnish obese children and the prevalence of cardiometabolic risk factors with child-specific cut-offs. This is a cross-sectional register-based study of 2-18-year-old children (n = 900) evaluated for obesity in three hospitals in 2005-2012. Clinical and metabolic data were related to sex, age, puberty, and obesity grade and analyzed using chi-square and non-parametric tests. In 80% of cases at least one cardiovascular risk factor was present. Only 3% of subjects for whom complete metabolic data were available (n = 360) had no metabolic disorder. Systolic blood pressure was hypertensive in 50.2% and diastolic in 14.5% of the children. The youngest children had highest body mass index SD score. Obesity was more severe in boys than girls (p < 0.001). Hypertensive systolic blood pressure values (p = 0.012), prediabetes (p < 0.001), fatty liver (p < 0.001), and dyslipidemia (p = 0.025) were more prevalent in 15-18-year-old boys than girls. Most obese children in specialist care have cardiovascular risk factors; this indicates that earlier intervention is needed.

Metabolic profiles and lipoprotein lipid concentrations in non-obese and obese patients with polycystic ovarian disease.

PubMed

Mahabeer, S; Naidoo, C; Norman, R J; Jialal, I; Reddi, K; Joubert, S M

1990-10-01

Clinical parameters, androgen status and lipoprotein lipid profiles were assessed in 10 non-obese and 10 obese patients with polycystic ovarian disease (PCOD) and reference subjects matched for age, height and weight. Both obese and non-obese women with PCOD had significantly higher androgen levels when compared to the reference groups. When comparison of lipoprotein lipid profiles were made between groups, non-obese women with PCOD had significantly higher total cholesterol, triglycerides and LDL-cholesterol levels than non-obese reference subjects. Obese PCOD women manifested significantly higher total cholesterol, LDL-cholesterol, cholesterol/HDL, and LDL/HDL values than did obese reference subjects. Correlations between serum androgens and lipoprotein lipid concentrations in PCOD and normal women were unhelpful. Both non-obese and obese patients with PCOD had significantly higher systolic and diastolic blood pressures (BPs) than the reference groups. Thus, both non-obese and obese women with PCOD manifest hyperandrogenaemia which may result in a male pattern of lipoprotein lipid concentrations.

Food Reinforcement and Parental Obesity Predict Future Weight Gain in Non-Obese Adolescents

PubMed Central

Epstein, Leonard H.; Yokum, Sonja; Feda, Denise M.; Stice, Eric

2014-01-01

Background Food reinforcement, the extent to which people are willing to work to earn a preferred snack food, and parental obesity are risk factors for weight gain, but there is no research comparing the predictive effects of these factors for adolescent weight gain. Methods 130 non-obese adolescents (M age = 15.2 ± 1.0; M BMI = 20.7 ± 2.0; M zBMI = 0.16 ± 0.64) at differential risk for weight gain based on parental obesity completed baseline food and money reinforcement tasks, and provided zBMI data over 2-yr follow-up. Results The number of obese (BMI ≥ 30) parents (p = 0.007) and high food reinforcement (p = 0.046) were both significant independent predictors of greater zBMI increases, controlling for age, sex, parent education and minority status. Having no obese parents or being low or average in food reinforcement was associated with reductions in zBMI, but those high in food reinforcement showed larger zBMI increases (0.102) than having one obese parent (0.025) but less than having two obese parents (0.177). Discussion Food reinforcement and parental obesity independently predict future weight gain among adolescents. It might be fruitful for obesity prevention programs to target both high risk groups. PMID:25045864

Obesity in the news: do photographic images of obese persons influence antifat attitudes?

PubMed

McClure, Kimberly J; Puhl, Rebecca M; Heuer, Chelsea A

2011-04-01

News coverage of obesity has increased dramatically in recent years, and research shows that media content may contribute to negative public attitudes toward obese people. However, no work has assessed whether photographic portrayals of obese people that accompany news stories affect attitudes. In the present study, the authors used a randomized experimental design to test whether viewing photographic portrayals of an obese person in a stereotypical or unflattering way (versus a nonstereotypical or flattering portrayal) could increase negative attitudes about obesity, even when the content of an accompanying news story is neutral. The authors randomly assigned 188 adult participants to read a neutral news story about the prevalence of obesity that was paired with 1 of 4 photographic portrayals of an obese adult (or no photograph). The authors subsequently assessed attitudes toward obese people using the Fat Phobia Scale. Participants in all conditions expressed a moderate level of fat phobia (M = 3.83, SD = 0.58). Results indicated that participants who viewed the negative photographs expressed more negative attitudes toward obese people than did those who viewed the positive photographs. Implications of these findings for the media are discussed, with emphasis on increasing awareness of weight bias in health communication and journalistic news reporting.

Perception of the child's obesity in parents of girls and boys treated for obesity (preliminary study).

PubMed

Radoszewska, Joanna

2014-01-01

The aim of this study is to analyze how the parents of children treated for obesity perceive the child's obesity and to search psychological determinants of persistence of obesity in children despite of treatment Material and methods: 15 mothers and 15 fathers of children treated for obesity participated in the study. The age of their children ranged from 7 to 9 years. The average age of the studied children was 8.1 years. Clinical interview concerning mental child representation in mother/father was used to collect the data. The parents of children treated for obesity concentrate on description of the child's obesity (eg referring to obesity related behaviors and physical appearance). Majority of statements contained negative content. Mothers of girls as well as of boys with obesity see the problem primarily in the child's behavior related to over-eating. The parents of children treated for obesity express parents' attitude towards the child's obesity (eg parent's emotional attitude towards the child's obesity or source of child's obesity).They worry and fear about social and health consequence of obesity. Some parents attribute the fault for obesity in the child. An increased number of symptoms of anxiety, helplessness in parents may affect the quality of the child's relationship with mother and father. Mothers of girls more frequently indicate the daughters' obesity as an obstacle in their relationship. Obesity is perceived not only as a somatic problem but also as an interpersonal one. Mothers and fathers of girls with obesity describe the child's obesity and express their attitude towards it more often than mothers and fathers of boys with obesity. This may be conditioned by the lower social acceptance of obesity in woman than man. 1. It is paramount in treating children for obesity, to consider the parents' emotional attitude towards the child's problem and their awareness of its presence; 2. Taking note of parents' understanding of the complexity of the

The use of measures of obesity in childhood for predicting obesity and the development of obesity-related diseases in adulthood: a systematic review and meta-analysis.

PubMed

Simmonds, Mark; Burch, Jane; Llewellyn, Alexis; Griffiths, Claire; Yang, Huiqin; Owen, Christopher; Duffy, Steven; Woolacott, Nerys

2015-06-01

It is uncertain which simple measures of childhood obesity are best for predicting future obesity-related health problems and the persistence of obesity into adolescence and adulthood. To investigate the ability of simple measures, such as body mass index (BMI), to predict the persistence of obesity from childhood into adulthood and to predict obesity-related adult morbidities. To investigate how accurately simple measures diagnose obesity in children, and how acceptable these measures are to children, carers and health professionals. Multiple sources including MEDLINE, EMBASE and The Cochrane Library were searched from 2008 to 2013. Systematic reviews and a meta-analysis were carried out of large cohort studies on the association between childhood obesity and adult obesity; the association between childhood obesity and obesity-related morbidities in adulthood; and the diagnostic accuracy of simple childhood obesity measures. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and a modified version of the Quality in Prognosis Studies (QUIPS) tool. A systematic review and an elicitation exercise were conducted on the acceptability of the simple measures. Thirty-seven studies (22 cohorts) were included in the review of prediction of adult morbidities. Twenty-three studies (16 cohorts) were included in the tracking review. All studies included BMI. There were very few studies of other measures. There was a strong positive association between high childhood BMI and adult obesity [odds ratio 5.21, 95% confidence interval (CI) 4.50 to 6.02]. A positive association was found between high childhood BMI and adult coronary heart disease, diabetes and a range of cancers, but not stroke or breast cancer. The predictive accuracy of childhood BMI to predict any adult morbidity was very low, with most morbidities occurring in adults who were of healthy weight in childhood. Predictive accuracy of childhood obesity was moderate for

Obesity and kidney protection

PubMed Central

Chandra, Aravind; Biersmith, Michael; Tolouian, Ramin

2014-01-01

Context: Obesity, both directly and indirectly, increases the risk for a variety of disease conditions including diabetes, hypertension, liver disease, and certain cancers, which in turn, decreases the overall lifespan in both men and women. Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. Results: The concept of the “Metabolic Syndrome“ helps us to understand this close link between obesity, diabetes, hypertension, and renal dysfunction. An elevated body mass index has shown to be one of the major determinants of glomerular hyperfiltration that lead to the development of chronic kidney disease. Interestingly, weight loss can lead to attenuation of hyperfiltration in severely obese patients suggesting a possible therapeutic option to combat obesity-related hyperfiltration. Conclusions: Various treatment strategies had been suggested to decrease impact of obesity on kidneys. These are blood pressure controling, inhibition of the renin-angiotensinaldosterone axis, improving glycemic control, improving dyslipidemia, improving protein uriaand lifestyle modifications. Regardless of the numerous pharmacotherapies, the focus should be on the root cause: obesity. PMID:25093156

Obesity and kidney protection.

PubMed

Chandra, Aravind; Biersmith, Michael; Tolouian, Ramin

2014-07-01

Obesity, both directly and indirectly, increases the risk for a variety of disease conditions including diabetes, hypertension, liver disease, and certain cancers, which in turn, decreases the overall lifespan in both men and women. Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. The concept of the "Metabolic Syndrome" helps us to understand this close link between obesity, diabetes, hypertension, and renal dysfunction. An elevated body mass index has shown to be one of the major determinants of glomerular hyperfiltration that lead to the development of chronic kidney disease. Interestingly, weight loss can lead to attenuation of hyperfiltration in severely obese patients suggesting a possible therapeutic option to combat obesity-related hyperfiltration. Various treatment strategies had been suggested to decrease impact of obesity on kidneys. These are blood pressure controling, inhibition of the renin-angiotensinaldosterone axis, improving glycemic control, improving dyslipidemia, improving protein uriaand lifestyle modifications. Regardless of the numerous pharmacotherapies, the focus should be on the root cause: obesity.

Association of FTO rs9939609 with Obesity.

PubMed

Yasri, Sora; Wiwanitkit, Viroj

2018-05-30

Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity

Materials (Subjects) and Methods

Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity

Results:

Association of FTO rs9939609 with Obesity

Conclusion:

Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity Association of FTO rs9939609 with Obesity. ©2018The Author(s). Published by S. Karger AG, Basel.

Chronic hyperinsulinemia contributes to insulin resistance under dietary restriction in association with altered lipid metabolism in Zucker diabetic fatty rats.

PubMed

Morita, Ippei; Tanimoto, Keiichi; Akiyama, Nobuteru; Naya, Noriyuki; Fujieda, Kumiko; Iwasaki, Takanori; Yukioka, Hideo

2017-04-01

Hyperinsulinemia is widely thought to be a compensatory response to insulin resistance, whereas its potentially causal role in the progression of insulin resistance remains to be established. Here, we aimed to examine whether hyperinsulinemia could affect the progression of insulin resistance in Zucker fatty diabetic (ZDF) rats. Male ZDF rats at 8 wk of age were fed a diet ad libitum (AL) or dietary restriction (DR) of either 15 or 30% from AL feeding over 6 wk. Insulin sensitivity was determined by hyperinsulinemic euglycemic clamp. ZDF rats in the AL group progressively developed hyperglycemia and hyperinsulinemia by 10 wk of age, and then plasma insulin rapidly declined to nearly normal levels by 12 wk of age. Compared with AL group, DR groups showed delayed onset of hyperglycemia and persistent hyperinsulinemia, leading to weight gain and raised plasma triglycerides and free fatty acids by 14 wk of age. Notably, insulin sensitivity was significantly reduced in the DR group rather than the AL group and inversely correlated with plasma levels of insulin and triglyceride but not glucose. Moreover, enhanced lipid deposition and upregulation of genes involved in lipogenesis were detected in liver, skeletal muscle, and adipose tissues of the DR group rather than the AL group. Alternatively, continuous hyperinsulinemia induced by insulin pellet implantation produced a decrease in insulin sensitivity in ZDF rats. These results suggest that chronic hyperinsulinemia may lead to the progression of insulin resistance under DR conditions in association with altered lipid metabolism in peripheral tissues in ZDF rats. Copyright © 2017 the American Physiological Society.

[Obese Hungary. Trend and prevalence of overweight and obesity in Hungary, 2015].

PubMed

Rurik, Imre; Ungvári, Tímea; Szidor, Judit; Torzsa, Péter; Móczár, Csaba; Jancsó, Zoltán; Sándor, János

2016-07-01

The prevalence of obesity is growing continuously worldwide, even in Hungary. Since 1988, when the first professional wide-range evaluation was performed, only limited data are available. Authors present the results of the ever largest Hungarian obesity-prevalence surveys, performed by family and occupational physicians. Data from 0.55% of the population above 18 year were registered in all geographical regions of Hungary (43,287 persons; 17,901 males and 25,386 females), close to the proper national representativeness. Age, body mass index, waist circumference, educational level, presence of hypertension and/or diabetes were analyzed statistically and compared with previous data. The overall prevalence rate of overweight and obesity among men was 40% and 32%, respectively, while overweight and obesity occurred in 32% of women. In the different age groups of men, the prevalence of overweight and obesity was: 32.7% and 18.2% in 18-34 years; 40.1% and 34.4% in 35-59 years; 43.5% and 38.8% in over 60 years, respectively. In the same age groups of women, overweight and obesity occurred in 19.6% and 15.7%, 36.8% and 38.7%, and 36.5% and 39.7%, respectively. Body mass index and waist-circumference were presented according to age, by decades and by type of residency as well. The highest ratio of overweight was registered among men with the highest educational level, while highest ratio of obesity among women having the lowest education. Obesity according to Body mass index and abdominal obesity was the highest in the villages, especially among females. Registered metabolic morbidities were strongly correlated with body mass index and both were inversely related to the level of urbanization. Over the previous decades, the ratio of the overweight and even the number of obese persons increased significantly, and it was most prominent among males, mainly in younger generation. Obesity means a serious medical, public health and economic problem, and it requires higher public

Obesity in show cats.

PubMed

Corbee, R J

2014-12-01

Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

[Obesity and heart failure].

PubMed

Weismann, D; Wiedmann, S; Bala, M; Frantz, S; Fassnacht, M

2015-02-01

Obesity is an important risk factor for the development of heart failure. In normotensive obese patients, a reduced peripheral resistance is typically observed and is accompanied by an increased fluid volume and an increase in cardiac work, resulting in hypertrophy and diastolic heart failure, which can be visualized with echocardiography. However, in the presence of arterial hypertension cardiac geometry is not different to hypertensive heart disease without obesity. Furthermore, the typical changes found with obesity, such as reduced peripheral resistance and increased blood volume, are no longer present. Obstructive sleep apnea (OSA) is very common in obesity and warrants screening but levels of the heart failure marker N-terminal pro-brain natriuretic peptide (NT-ProBNP) might be misleading as the values are lower in obesity than in normal weight controls. Body weight reduction is advisable but difficult to achieve and much more difficult to maintain. Furthermore, diet and exercise has not been proven to enhance life expectancy in obesity. However, with bariatric surgery, long-term weight reduction can be achieved and mortality can be reduced. With effective weight loss and improved clinical outcome after bariatric surgery, treatment of obesity has shifted much more into focus. Regardless of technical challenges in the work-up of obese patients, clinical symptoms suggestive of cardiac disorders warrant prompt investigation with standard techniques following recommendations as established for normal weight patients.

Obesity in the new media: a content analysis of obesity videos on YouTube.

PubMed

Yoo, Jina H; Kim, Junghyun

2012-01-01

This study examines (1) how the topics of obesity are framed and (2) how obese persons are portrayed on YouTube video clips. The analysis of 417 obesity videos revealed that a newer medium like YouTube, similar to traditional media, appeared to assign responsibility and solutions for obesity mainly to individuals and their behaviors, although there was a tendency that some video categories have started to show other causal claims or solutions. However, due to the prevailing emphasis on personal causes and solutions, numerous YouTube videos had a theme of weight-based teasing, or showed obese persons engaging in stereotypical eating behaviors. We discuss a potential impact of YouTube videos on shaping viewers' perceptions about obesity and further reinforcing stigmatization of obese persons.

Epigenetics and human obesity.

PubMed

van Dijk, S J; Molloy, P L; Varinli, H; Morrison, J L; Muhlhausler, B S

2015-01-01

Recent technological advances in epigenome profiling have led to an increasing number of studies investigating the role of the epigenome in obesity. There is also evidence that environmental exposures during early life can induce persistent alterations in the epigenome, which may lead to an increased risk of obesity later in life. This paper provides a systematic review of studies investigating the association between obesity and either global, site-specific or genome-wide methylation of DNA. Studies on the impact of pre- and postnatal interventions on methylation and obesity are also reviewed. We discuss outstanding questions, and introduce EpiSCOPE, a multidisciplinary research program aimed at increasing the understanding of epigenetic changes in emergence of obesity. An electronic search for relevant articles, published between September 2008 and September 2013 was performed. From the 319 articles identified, 46 studies were included and reviewed. The studies provided no consistent evidence for a relationship between global methylation and obesity. The studies did identify multiple obesity-associated differentially methylated sites, mainly in blood cells. Extensive, but small, alterations in methylation at specific sites were observed in weight loss intervention studies, and several associations between methylation marks at birth and later life obesity were found. Overall, significant progress has been made in the field of epigenetics and obesity and the first potential epigenetic markers for obesity that could be detected at birth have been identified. Eventually this may help in predicting an individual's obesity risk at a young age and opens possibilities for introducing targeted prevention strategies. It has also become clear that several epigenetic marks are modifiable, by changing the exposure in utero, but also by lifestyle changes in adult life, which implies that there is the potential for interventions to be introduced in postnatal life to modify

Childhood Obesity Causes & Consequences

MedlinePlus

... and Local Programs Related Topics Diabetes Nutrition Childhood Obesity Causes & Consequences Recommend on Facebook Tweet Share Compartir ... determine how a community is designed. Consequences of Obesity More Immediate Health Risks Obesity during childhood can ...

Obesity and Asian Americans

MedlinePlus

... and Data > Minority Population Profiles > Asian American > Obesity Obesity and Asian Americans Non-Hispanic whites are 60% ... youthonline . [Accessed 08/18/2017] HEALTH IMPACT OF OBESITY People who are overweight are more likely to ...

Obesity and African Americans

MedlinePlus

... Data > Minority Population Profiles > Black/African American > Obesity Obesity and African Americans African American women have the ... youthonline . [Accessed 08/18/2017] HEALTH IMPACT OF OBESITY People who are overweight are more likely to ...

Obesity and Hispanic Americans

MedlinePlus

... and Data > Minority Population Profiles > Hispanic/Latino > Obesity Obesity and Hispanic Americans Among Mexican American women, 77 ... youthonline . [Accessed 08/18/2017] HEALTH IMPACT OF OBESITY People who are overweight are more likely to ...

Metabolic syndrome and its characteristics among obese patients attending an obesity clinic.

PubMed

Termizy, H M; Mafauzy, M

2009-04-01

The increased prevalence of metabolic syndrome worldwide is closely related to the rising obesity epidemic. The objectives of the study were to determine the prevalence and identify the associated and prognostic factors that influence the risk of metabolic syndrome among obese patients attending the Obesity Clinic at Hospital Universiti Sains Malaysia. A study was conducted involving 102 obese persons who attended the Obesity Clinic from January 1 to December 31, 2005. Metabolic syndrome was defined according to the International Diabetes Federation criteria. The overall prevalence of metabolic syndrome among obese patients was 40.2 percent. The prevalence was higher in females (43.7 percent) than in males (32.3 percent). The prevalence of metabolic syndrome was noted to increase with increasing body mass index class, from class 1 to class 2. However, the prevalence was lower in obesity class 3. The prevalence of metabolic comorbidities of raised blood pressure, reduced high density lipoprotein, high triglyceride and raised fasting blood glucose was 42, 40, 36 and 17 percent, respectively. A quarter of obese patients in this study had no other comorbidity. Based on logistic regression multivariable analysis, age was the only significant associated factor that influenced the risk of having metabolic syndrome. The prevalence of metabolic syndrome was high and the highest comorbidity was high blood pressure. Age was the only significant risk factor of having this syndrome.

[Genetic obesity: new diagnostic options].

PubMed

de Vries, T I; Alsters, S I M; Kleinendorst, L; van Haaften, G; van der Zwaag, B; Van Haelst, M M

2017-01-01

- Obesity is an important risk factor for morbidity and premature death, as well as a contributing factor to psychosocial problems. The incidence of obesity has increased dramatically over the last few decades.- Obesity is considered to be a multifactorial condition in which both environmental factors and genetic factors play a part.- In approximately 5% of patients with morbid obesity, a monogenic cause can be identified. Mutations in the MC4R gene are the most frequently occurring monogenic cause of obesity.- The department of Genetics at the VU University Medical Center Amsterdam offers morbidly obese patients a diagnostic analysis of 50 obesity-associated genes. - An underlying obesity-associated genetic defect can influence patient response to certain treatments. Therefore, if the gene defect is known, it can be taken into account when considering treatment options.- The understanding of the genetics of obesity will significantly contribute to research into the development of personalized treatment options.

Contraception and the obese woman

PubMed Central

Reifsnider, Elizabeth; Mendias, Nonie; Davila, Yolanda; Babendure, Jennie Bever

2016-01-01

Purpose Obesity has reached epidemic rates among U.S. women of reproductive age, many of whom want to use contraception. However, some forms of contraception can have adverse effects on an obese woman's health. This article explores risks of contraception available in the United States and provides clinical recommendations for use by obese women. Data sources Information was compiled by reviewing the scientific literature on contraception and female obesity using CINAHL, MEDLINE, PubMed search engines. Conclusions The evidence is largely supportive of combined oral contraceptive (COC) use in carefully screened obese women without known risks factors for cardiovascular disease. The efficacy of COCs may be slightly reduced in obese women because of increased body mass. Other types of hormonal contraceptives have varying safety and efficacy reports when used by obese women. Intrauterine devices do not have reduced efficacy nor increased risks for obese women but insertion may be more difficult. Obesity has no effect on efficacy of barrier methods of contraception. Implications Clinicians should conduct a careful history and physical exam with selected supporting laboratory tests when considering prescription of hormonal contraceptives for obese women. Obese women require health counseling to carefully follow directions for contraceptive use to avoid unintended pregnancy. PMID:24170564

Obesity and infection: reciprocal causality.

PubMed

Hainer, V; Zamrazilová, H; Kunešová, M; Bendlová, B; Aldhoon-Hainerová, I

2015-01-01

Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections.

Obesity and craniopharyngioma

PubMed Central

2011-01-01

An epidemic of pediatric obesity has occurred across the world in recent years. There are subgroups within the population at high-risk of becoming obese and especially of having experience of precocious cardiovascular and metabolic co-morbidities of obesity. One of these subgroups comprises patients treated for childhood cancers and namely survivors of craniopharyngioma. The high incidence of obesity in this group makes these patients an important disease model to better understand the metabolic disturbances and the mechanisms of weight gain among cancer survivors. The hypothalamic-pituitary axis damage secondary to cancer therapies or to primary tumor location affect long-term outcomes. Nevertheless, the aetiology of obesity in craniopharyngioma is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population. PMID:21846381

Overweight and Obesity (For Parents)

MedlinePlus

... Videos for Educators Search English Español Overweight and Obesity KidsHealth / For Parents / Overweight and Obesity What's in ... who lead by example. What Health Problems Can Obesity Cause? Obesity puts kids at risk for medical ...

Orexin: Pathways to obesity resistance?

PubMed Central

Butterick, Tammy A.; Billington, Charles J.; Kotz, Catherine M.; Nixon, Joshua P.

2016-01-01

Obesity has increased in prevalence worldwide, attributed in part to the influences of an obesity-promoting environment and genetic factors. While obesity and overweight increasingly seem to be the norm, there remain individuals who resist obesity. We present here an overview of data supporting the idea that hypothalamic neuropeptide orexin A (OXA; hypocretin 1) may be a key component of brain mechanisms underlying obesity resistance. Prior work with models of obesity and obesity resistance in rodents has shown that increased orexin and/or orexin sensitivity is correlated with elevated spontaneous physical activity (SPA), and that orexin-induced SPA contributes to obesity resistance via increased non-exercise activity thermogenesis (NEAT). However, central hypothalamic orexin signaling mechanisms that regulate SPA remain undefined. Our ongoing studies and work of others support the hypothesis that one such mechanism may be upregulation of a hypoxia-inducible factor 1 alpha (HIF-1α)-dependent pathway, suggesting that orexin may promote obesity resistance both by increasing SPA and by influencing the metabolic state of orexin-responsive hypothalamic neurons. We discuss potential mechanisms based on both animal and in vitro pharmacological studies, in the context of elucidating potential molecular targets for obesity prevention and therapy. PMID:24005942

Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure.

PubMed

Lavie, Carl J; Alpert, Martin A; Arena, Ross; Mehra, Mandeep R; Milani, Richard V; Ventura, Hector O

2013-04-01

Obesity has reached epidemic proportions in the United States and worldwide. Considering the adverse effects of obesity on left ventricular (LV) structure, diastolic and systolic function, and other risk factors for heart failure (HF), including hypertension and coronary heart disease, HF incidence and prevalence, not surprisingly, is markedly increased in obese patients. Nevertheless, as with most other cardiovascular diseases, numerous studies have documented an obesity paradox, in which overweight and obese patients, defined by body mass index, percent body fat, or central obesity, demonstrate a better prognosis compared with lean or underweight HF patients. This review will describe the data on obesity in the context of cardiopulmonary exercise testing in HF. Additionally, the implications of obesity on LV assist devices and heart transplantation are reviewed. Finally, despite the obesity paradox, we address the current state of weight reduction in HF. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Childhood obesity for pediatric gastroenterologists.

PubMed

Huang, Jeannie S; Barlow, Sarah E; Quiros-Tejeira, Ruben E; Scheimann, Ann; Skelton, Joseph; Suskind, David; Tsai, Patrika; Uko, Victor; Warolin, Joshua P; Xanthakos, Stavra A

2013-01-01

Obesity in childhood is one of the major health issues in pediatric health care today. As expected, the prevalence of obesity-related comorbidities has risen in parallel with that of obesity. Consultation regarding these concomitant diseases and subsequent management by subspecialists, including pediatric gastroenterologists, is now common and has resulted in obesity being recognized as a chronic disease requiring coordination of care. Although medications and even surgery may provide effective, though often temporary, treatments for obesity and its comorbidities, behavioral interventions addressing healthy dietary and physical activity habits remain a mainstay in the obesity treatment paradigm. Therefore, the issue of weight management must be addressed by both general practitioner and subspecialist alike. In this report, we review select aspects of pediatric obesity and obesity-related management issues because it relates in particular to the field of pediatric gastroenterology and hepatology.

Childhood Obesity for Pediatric Gastroenterologists

PubMed Central

Huang, Jeannie S.; Barlow, Sarah E.; Quiros-Tejeira, Ruben E.; Scheimann, Ann; Skelton, Joseph; Suskind, David; Tsai, Patrika; Uko, Victor; Warolin, Joshua P.; Xanthakos, Stavra A.

2014-01-01

Obesity in childhood is one of the major health issues in pediatric health care today. As expected, the prevalence of obesity-related comorbidities has risen in parallel with that of obesity. Consultation regarding these concomitant diseases and subsequent management by subspecialists, including pediatric gastroenterologists, is now common and has resulted in obesity being recognized as a chronic disease requiring coordination of care. Although medications and even surgery may provide effective, though often temporary, treatments for obesity and its comorbidities, behavioral interventions addressing healthy dietary and physical activity habits remain a mainstay in the obesity treatment paradigm. Therefore, the issue of weight management must be addressed by both general practitioner and subspecialist alike. In this report, we review select aspects of pediatric obesity and obesity-related management issues because it relates in particular to the field of pediatric gastroenterology and hepatology. PMID:23282941

Comparison of serum androgens and endometrial thickness in obese and non-obese postmenopausal women

PubMed Central

Arıkan, İlker İnan; Barut, Aykut; Arıkan, Deniz; Harma, Müge; Harma, Mehmet İbrahim; Bozkurt, Serpil

2010-01-01

Objective In this study, we investigated whether serum androgen levels and endometrial thickness differed in obese and non-obese women. Material and Methods Thirtytwo non-obese (BMI <30) and 48 obese (BMI ≥ 30) women were enrolled. Blood samples were analyzed for testosterone, free testosterone, androstenedione, DHEAS, and SHBG, and transvaginal ultrasonography was performed. Results Obese women had significantly higher free testosterone and endometrial thickness and significantly lower SHBG. Eight of 17 women with endometrial thickness >5 mm had significant pathology. Conclusion These results suggest that obesity may be a risk factor for endometrial carcinoma and other pathologies in post-menopausal women through an action on androgen concentrations. PMID:24591922

Epigenetic regulation in obesity.

PubMed

Drummond, Elaine M; Gibney, Eileen R

2013-07-01

Research suggests that 65% of variation in obesity is genetic. However, much of the known genetic associations have little known function and their effect size small, thus the gene-environment interaction, including epigenetic influences on gene expression, is suggested to be an important factor in the susceptibilty to obesity. This review will explore the potential of epigenetic markers to influence expression of genes associated with obesity. Epigenetic changes in utero are known to have direct implications on the phenotype of the offspring. More recently work has focused on how such epigenetic changes continue to regulate risk of obesity from infancy through to adulthood. Work has shown that, for example, hypomethylation of the MC4 gene causes an increase in expression, and has a direct impact on appetite and intake, and thus influences risk of obesity. Similar influences are also seen in other aspects of obesity including inflammation and adiposity. Maternal diet during foetal development has many epigenetic implications, which affect the offspring's risk factors for obesity during childhood and adulthood, and even in subsequent generations. Genes associated with risk of obesity, are susceptible to epigenetic mutations, which have subsequent effects on disease mechanisms, such as appetite and impaired glucose and insulin tolerance.

Epigenetics of Obesity.

PubMed

Lopomo, A; Burgio, E; Migliore, L

2016-01-01

Obesity is a metabolic disease, which is becoming an epidemic health problem: it has been recently defined in terms of Global Pandemic. Over the years, the approaches through family, twins and adoption studies led to the identification of some causal genes in monogenic forms of obesity but the origins of the pandemic of obesity cannot be considered essentially due to genetic factors, because human genome is not likely to change in just a few years. Epigenetic studies have offered in recent years valuable tools for the understanding of the worldwide spread of the pandemic of obesity. The involvement of epigenetic modifications-DNA methylation, histone tails, and miRNAs modifications-in the development of obesity is more and more evident. In the epigenetic literature, there are evidences that the entire embryo-fetal and perinatal period of development plays a key role in the programming of all human organs and tissues. Therefore, the molecular mechanisms involved in the epigenetic programming require a new and general pathogenic paradigm, the Developmental Origins of Health and Disease theory, to explain the current epidemiological transition, that is, the worldwide increase of chronic, degenerative, and inflammatory diseases such as obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer. Obesity and its related complications are more and more associated with environmental pollutants (obesogens), gut microbiota modifications and unbalanced food intake, which can induce, through epigenetic mechanisms, weight gain, and altered metabolic consequences. Copyright © 2016 Elsevier Inc. All rights reserved.

[Eating disorders and obesity].

PubMed

Wolf, L M; Houdent, C

1989-02-16

In most cases, obesity does not stem from a specific psychologic disturbance. Some obese people overeat, as do their family or their socio-professional peers, and this cannot be considered a pathologic behaviour. Many obese patients increase their energy intake when frustrated, anxious, or tired, like many normal individuals who enjoy a better weight regulation. But when obesity increases suddenly and/or severely in these circumstances, and in gross obesity, abnormal feeding behaviour is usually responsible: prandial or, more often extraprandial overeating (nibbling, gorging, binge eating, night eating, excess alcohol, carbohydrate craving). Serotoninergic mechanisms of the latter have focused wide interest. Conflicting situations and/or anxiety are usually a factor in child obesity. Deppreciated self-image and feelings of culpability, partly secondary to obesity itself and dietary failures often contribute to feeding disturbances, sometimes surreptitious, carrying a risk of vicious circle. But weight reduction itself, while improving self image, carries a risk of unmasking depressive tendencies, especially when too quick. Hence the importance of careful and comprehensive management.

Reimagining Obesity

ERIC Educational Resources Information Center

Schultz, Jaime

2017-01-01

This article draws on Mills' sociological imagination (from the 1959 publication "The Sociological Imagination") to consider the connections between personal trouble and social issues when it comes to the causes and consequences of obesity. These connections may be important for assuaging the "obesity bias" that pervades our…

Obesity Prevention and Screening.

PubMed

Mackey, Eleanor R; Olson, Alexandra; DiFazio, Marc; Cassidy, Omni

2016-03-01

Obesity is widespread, associated with several physical and psychosocial comorbidities, and is difficult to treat. Prevention of obesity across the lifespan is critical to improving the health of individuals and society. Screening and prevention efforts in primary care are an important step in addressing the obesity epidemic. Each period of human development is associated with unique risks, challenges, and opportunities for prevention and intervention. Screening tools for overweight/obesity, although imperfect, are quick and easy to administer. Screening should be conducted at every primary care visit and tracked longitudinally. Screening tools and cutoffs for overweight and obesity vary by age group. Copyright © 2016 Elsevier Inc. All rights reserved.

Economics and obesity policy.

PubMed

Lusk, J L

2017-06-01

This paper elucidates the challenges surrounding the economics of some popular obesity-related policy proposals. Solid economic justifications for anti-obesity policies are often lacking, and evidence suggests policies like fat and soda taxes or restrictions on food stamp spending are unlikely to substantively affect obesity prevalence. In short, many of the same factors that make obesity such a complicated and multifaceted issue extend to the economic analysis of public health policies.

Workplace obesity prevention.

PubMed

Chalupka, Stephanie

2011-05-01

Employers can effectively reduce obesity, lower their health care costs, reduce absenteeism, and increase employee productivity through workplace obesity prevention programs. Copyright 2011, SLACK Incorporated.

Genetics of obesity.

PubMed

O'Rahilly, Stephen; Farooqi, I Sadaf

2006-07-29

Considerable attention is currently being paid to the secular changes in food intake and physical activity that underlie the increase in the prevalence of obesity that is apparent in many societies. While this is laudable it would be unwise to view these environmental factors in isolation from the biological factors that normally control body weight and composition and the compelling evidence that inter-individual differences in susceptibility to obesity have strong genetic determinants. This is particularly important, as it is only in the past decade that we have begun to obtain substantive information regarding the molecular constituents of pathways controlling mammalian energy balance and therefore, for the first time, are in a position to achieve a better mechanistic understanding of this disease. Population-based association and linkage studies have highlighted a number of loci at which genetic variation is associated with obesity and related phenotypes and the identification and characterization of monogenic obesity syndromes has been particularly fruitful. While there is widespread acceptance that hereditary factors might predispose to human obesity, it is frequently assumed that such factors would influence metabolic rate or the selective partitioning of excess calories into fat. However, it is notable that, thus far, all monogenic defects causing human obesity actually disrupt hypothalamic pathways and have a profound effect on satiety and food intake. To conclude, the evidence we have to date suggests that the major impact of genes on human obesity is just as likely (or perhaps more likely) to directly impact on hunger, satiety and food intake rather than metabolic rate or nutrient partitioning. At the risk of oversimplification, it seems that from an aetiological/genetic standpoint, human obesity appears less a metabolic than a neuro-behavioural disease.

Dietary fiber in the prevention and treatment of metabolic syndrome: a review.

PubMed

Aleixandre, Amaya; Miguel, Marta

2008-11-01

Inclusion of fiber in the diet has been linked to the prevention of a range of illnesses and conditions. This review contains several ideas about the possible benefits of dietary fiber intake in patients with metabolic syndrome. The principal beneficial effects of a fiber-rich diet in these patients are: prevention of obesity, improved glucose levels, and control of the profile of blood lipids. We now also know that dietary fiber may favor the control of arterial blood pressure. Animal experiments have also shown the benefit of different types of fiber on these variables. Of particular relevance are the studies using obese Zucker rats, which present similar anomalies to those seen in patients with metabolic syndrome. There is therefore a growing interest in discovering new sources of natural fiber. Some of these different kinds of fiber may then be used as functional ingredients to obtain foods with properties that are beneficial to health.

American Board of Obesity Medicine (ABOM)

MedlinePlus

... form below to receive more information. PARTNERS Primary Obesity CME Columbia University Institute of Human Nutrition Harvard ... Obesity Medicine Obesity Medicine Association The Obesity Society Obesity-Related CME American Society for Metabolic and Bariatric ...

Obstructive Sleep Apnea: Differences between Normal-Weight, Overweight, Obese, and Morbidly Obese Children.

PubMed

Scott, Brian; Johnson, Romaine F; Mitchell Md, Ron B

2016-05-01

The severity of obstructive sleep apnea in children determines perioperative management and is an indication for postoperative polysomnography. The relationship between increasing weight and sleep apnea severity in children remains unclear. To compare demographic, clinical, and polysomnography parameters in normal-weight, overweight, obese, and morbidly obese children, as well as identify demographic factors that predict sleep apnea severity. Case series with chart review. Academic children's hospital. A retrospective chart review of 290 children aged 2 to 18 years who underwent polysomnography at an academic children's hospital was performed. Demographics, clinical findings, and polysomnographic parameters were recorded. Children were categorized as normal weight, overweight, obese, or morbidly obese. Differences were assessed using linear and logistical regression models. Significance was set at P < .05. Morbidly obese were older than normal-weight children (mean, 8.0 ± 0.5 years vs 5.8 ± 0.3 years; P < .001) and less likely to have a normal polysomnogram (16% vs 48%; P = .02). There were no differences in sex, ethnicity, birth status (term or preterm), or tonsil size between normal-weight, overweight, obese, and morbidly obese children. Sleep efficiency and percentage of time in rapid eye movement were decreased in morbidly obese compared with other children (P < .05). The apnea-hypopnea index was positively correlated with increasing body mass index z score only as a function of increasing age (P < .001). Obstructive sleep apnea severity is correlated with a combination of increasing age and weight but not with either variable independently. This study suggests that obese and morbidly obese older children are most likely to have severe obstructive sleep apnea. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Motor Skills of Obese and Severely Obese Children and Adolescents - A CIRCUIT Study.

PubMed

Häcker, Anna-Luisa; Bigras, Jean-Luc; Henderson, Mélanie; Barnett, Tracie A; Mathieu, Marie-Eve

2017-11-27

During childhood, excessive weight is negatively associated with the development of motor skills, with children with overweight or obesity having poorer motor skills compared to children with normal weight. The objectives of the current study are to identify the differences in motor skills between children and adolescent with obesity and severe obesity and the extent of this difference. To do so, we examined cross-sectionally 165 subjects. Physical fitness was analyzed in both participants with obesity (>97-99.9 BMI percentile) and severe obesity (>99.9 BMI percentile) using eight standardized tests: sit-and-reach, grip force, sit-ups, push-ups, balance, hand-eye coordination, standing long jump and 5-meter shuttle run. Poorer performance were observed in participants with severe obesity in sit-ups (children: 59%; 18.6±17.0 percentile value vs. 29.5±23.2 percentile value, p=0.008), balance (adolescent: 59%; 12.1±12.2 sec. v. 19.3±13.9 sec., p=0.034) and in the 5-meter shuttle run (children: 49%; 14.0±13.9 percentile value vs. 20.8 ± 19.4 percentile value, p=0.046; adolescents: 11%; 13.2±2.2 sec. vs. 11.8±1.6 sec., p=0.008) compared to obese counterparts. In conclusion, while physical performance was found to be similar between the different obesity levels for the majority of tests, youth with severe obesity demonstrated impairments ranging from 11 to 59% in specific tests.

Age-related consequences of childhood obesity.

PubMed

Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

2014-01-01

The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood.

Are Obese Patients at an Increased Risk of Pelvic Floor Dysfunction Compared to Non-obese Patients?

PubMed

Neto, Isaac José Felippe Corrêa; Pinto, Rodrigo Ambar; Jorge, José Marcio Neves; Santo, Marco Aurélio; Bustamante-Lopez, Leonardo Alfonso; Cecconello, Ivan; Nahas, Sérgio Carlos

2017-07-01

Factors associated with increased intra-abdominal pressure such as chronic cough, morbid obesity, and constipation may be related to pelvic floor dysfunction. In this study, we compared anorectal manometry values and clinical data of class II and III morbidly obese patients referred to bariatric surgery with that of non-obese patients. We performed a case-matched study between obese patients referred to bariatric surgery and non-obese patients without anorectal complaints. The groups were matched by age and gender. Men and nulliparous women with no history of abdominal or anorectal surgery were included in the study. Anorectal manometry was performed by the stationary technique, and clinical evaluation was based on validated questionnaires. Mean age was 44.8 ± 12.5 years (mean ± SD) in the obese group and 44.1 ± 11.8 years in the non-obese group (p = 0.829). In the obese group, 65.4% of patients had some degree of fecal incontinence. Mean squeeze pressure was significantly lower in obese than in non-obese patients (155.6 ± 64.1 vs. 210.1 ± 75.9 mmHg, p = 0.004), and there was no significant difference regarding mean rest pressure in obese patients compared to non-obese ones (63.7 ± 23.1 vs. 74.1 ± 21.8 mmHg, p = 0.051). There were no significant differences in anorectal manometry values between continent and incontinent obese patients. The prevalence of fecal incontinence among obese patients was high regardless of age, gender, and body mass index. Anal squeeze pressure was significantly lower in obese patients compared to non-obese controls.

A randomised controlled trial for overweight and obese parents to prevent childhood obesity--Early STOPP (STockholm Obesity Prevention Program).

PubMed

Sobko, Tanja; Svensson, Viktoria; Ek, Anna; Ekstedt, Mirjam; Karlsson, Håkan; Johansson, Elin; Cao, Yingting; Hagströmer, Maria; Marcus, Claude

2011-05-18

Overweight and obesity have a dramatic negative impact on children's health not only during the childhood but also throughout the adult life. Preventing the development of obesity in children is therefore a world-wide health priority. There is an obvious urge for sustainable and evidenced-based interventions that are suitable for families with young children, especially for families with overweight or obese parents. We have developed a prevention program, Early STOPP, combating multiple obesity-promoting behaviors such unbalanced diet, physical inactivity and disturbed sleeping patterns. We also aim to evaluate the effectiveness of the early childhood obesity prevention in a well-characterized population of overweight or obese parents. This protocol outlines methods for the recruitment phase of the study. This randomized controlled trial (RCT) targets overweight and/or obese parents with infants, recruited from the Child Health Care Centers (CHCC) within the Stockholm area. The intervention starts when infants are one year of age and continues until they are six and is regularly delivered by a trained coach (dietitian, physiotherapist or a nurse). The key aspects of Early STOPP family intervention are based on Swedish recommendations for CHCC, which include advices on healthy food choices and eating patterns, increasing physical activity/reducing sedentary behavior and regulating sleeping patterns. The Early STOPP trial design addresses weaknesses of previous research by recruiting from a well-characterized population, defining a feasible, theory-based intervention and assessing multiple measurements to validate and interpret the program effectiveness. The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge, this longitudinal RCT is the first attempt to demonstrate whether an early, long-term, targeted health promotion program focusing on healthy eating, physical activity/reduced sedentary behaviors and normalizing

Economic Differences in Risk Factors for Obesity among Overweight and Obese Children

ERIC Educational Resources Information Center

Kim, Hee Soon; Ham, Ok Kyung; Jang, Mi Na; Yun, Hyun Jung; Park, Jiyoung

2014-01-01

The purpose of the study was to identify the economic differences in familial, physiological, psychological, and lifestyle characteristics associated with overweight and obese children in South Korea. A total of 407 overweight and obese children participated in the study. The obesity rate was 69.0% and the prevalence of metabolic syndrome (MS) was…

Serum fetuin-A levels in obese and non-obese subjects with and without type 2 diabetes mellitus.

PubMed

Zhou, Zhong-Wei; Ju, Hui-Xiang; Sun, Ming-Zhong; Chen, Hong-Mei; Fu, Qing-Ping; Jiang, Dong-Mei

2018-01-01

Higher fetuin-A expression is linked to both obesity and type 2 diabetes mellitus (T2DM), However, studies in non-obese patients with T2DM are scarce. 345 newly diagnosed T2DM patients and 300 subjects with normal glucose tolerance (NGT) were divided into obese and non-obese subgroups, respectively. Serum fetuin-A and adiponectin levels and related parameters were measured. T2DM patients with obesity had higher fetuin-A levels compared with non-obese patients and obese NGT subjects (p<0.001). Significant correlations were observed between fetuin-A and most metabolic parameters in obese NGT and T2DM subjects, but which was not in non-obese patients with T2DM. The independent associations were found between fetuin-A and free fatty acids, HOMA-IR, C-reactive protein and adiponectin only in obese NGT and T2DM subjects (all p<0.05). The adjusted odds ratios for obesity were increased with increasing quartile of fetuin-A in both T2DM and NGT subjects in logistic regression models (p for trend<0.001), but which was more significant in T2DM patients. Higher serum fetuin-A levels in obese T2DM patients compared with non-obese patients and obese NGT subjects supports the hypothesis that fetuin-A may be as a bridge connecting obesity and obesity-related T2DM. Copyright © 2017 Elsevier B.V. All rights reserved.

Childhood obesity: causes and consequences.

PubMed

Sahoo, Krushnapriya; Sahoo, Bishnupriya; Choudhury, Ashok Kumar; Sofi, Nighat Yasin; Kumar, Raman; Bhadoria, Ajeet Singh

2015-01-01

Childhood obesity has reached epidemic levels in developed as well as in developing countries. Overweight and obesity in childhood are known to have significant impact on both physical and psychological health. Overweight and obese children are likely to stay obese into adulthood and more likely to develop non-communicable diseases like diabetes and cardiovascular diseases at a younger age. The mechanism of obesity development is not fully understood and it is believed to be a disorder with multiple causes. Environmental factors, lifestyle preferences, and cultural environment play pivotal roles in the rising prevalence of obesity worldwide. In general, overweight and obesity are assumed to be the results of an increase in caloric and fat intake. On the other hand, there are supporting evidence that excessive sugar intake by soft drink, increased portion size, and steady decline in physical activity have been playing major roles in the rising rates of obesity all around the world. Childhood obesity can profoundly affect children's physical health, social, and emotional well-being, and self esteem. It is also associated with poor academic performance and a lower quality of life experienced by the child. Many co-morbid conditions like metabolic, cardiovascular, orthopedic, neurological, hepatic, pulmonary, and renal disorders are also seen in association with childhood obesity.

Gastrointestinal Complications of Obesity

PubMed Central

Camilleri, Michael; Malhi, Harmeet; Acosta, Andres

2017-01-01

Obesity usually is associated with morbidity related to diabetes mellitus and cardiovascular diseases. However, there are many gastrointestinal and hepatic diseases for which obesity is the direct cause (eg, nonalcoholic fatty liver disease) or is a significant risk factor, such as reflux esophagitis and gallstones. When obesity is a risk factor, it may interact with other mechanisms and result in earlier presentation or complicated diseases. There are increased odds ratios or relative risks of several gastrointestinal complications of obesity: gastroesophageal reflux disease, erosive esophagitis, Barrett’s esophagus, esophageal adenocarcinoma, erosive gastritis, gastric cancer, diarrhea, colonic diverticular disease, polyps, cancer, liver disease including nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, gallstones, acute pancreatitis, and pancreatic cancer. Gastroenterologists are uniquely poised to participate in the multidisciplinary management of obesity as physicians caring for people with obesity-related diseases, in addition to their expertise in nutrition and endoscopic interventions. PMID:28192107

Ciliary dysfunction and obesity.

PubMed

Mok, C A; Héon, E; Zhen, M

2010-01-01

Obesity associates with increased health risks such as heart disease, stroke and diabetes. The steady rise in the obese population worldwide poses an increasing burden on health systems. Genetic factors contribute to the development of obesity, and the elucidation of their physiological functions helps to understand the cause, and improve the prevention, diagnosis and treatment for this disorder. Primary cilia are evolutionarily conserved organelles whose dysfunctions lead to human disorders now defined as ciliopathies. Human ciliopathies present pleiotropic and overlapping phenotypes that often include retinal degeneration, cystic renal anomalies and obesity. Increasing evidence implicates an intriguing involvement of cilia in lipid/energy homeostasis. Here we discuss recent studies in support of the key roles of ciliary genes in the development and pathology of obesity in various animal models. Genes affecting ciliary development and function may pose promising candidate underlying genetic factors that contribute to the development of common obesity.

Thinking Evolutionarily About Obesity

PubMed Central

Genné-Bacon, Elizabeth A.

2014-01-01

Obesity, diabetes, and metabolic syndrome are growing worldwide health concerns, yet their causes are not fully understood. Research into the etiology of the obesity epidemic is highly influenced by our understanding of the evolutionary roots of metabolic control. For half a century, the thrifty gene hypothesis, which argues that obesity is an evolutionary adaptation for surviving periods of famine, has dominated the thinking on this topic. Obesity researchers are often not aware that there is, in fact, limited evidence to support the thrifty gene hypothesis and that alternative hypotheses have been suggested. This review presents evidence for and against the thrifty gene hypothesis and introduces readers to additional hypotheses for the evolutionary origins of the obesity epidemic. Because these alternate hypotheses imply significantly different strategies for research and clinical management of obesity, their consideration is critical to halting the spread of this epidemic. PMID:24910556

Prevalence of overweight, obesity, abdominal-obesity and short stature of adult population of Rosario, Argentina.

PubMed

Zapata, María Elisa; Bibiloni, María Del Mar; Tur, Josep A

2016-09-20

The aim of this work was to assess the prevalence of overweight, obesity, abdominal-obesity and short stature among Rosario (Argentina) adult population. A cross-sectional nutritional survey was carried out in Rosario (2012-2013). A random sample (n = 1194) of adult population (18-70 years old) was interviewed. Anthropometric measurements and a general questionnaire incorporating questions related to socio-demographic and lifestyle characteristics, education level and physical activity were used. The current study detected a high prevalence of overweight and obesity among adult population in Rosario. The prevalence of overweight was 32.7% (43.9% in men and 27.6% in women, p < 0.001), of obesity was 23.5% (21.6% in men and 24.3% in women), and of abdominal obesity was 57.5% (63.5% in men vs.54.8% in women, p < 0.005). Multivariate analysis showed that the prevalence of overweight/obesity and abdominal obesity increased according the age and abdominal obesity decreased with high physical activity in men. In women prevalence of overweight/obesity, and abdominal obesity increased with age, marital status (married or coupled), presence of at least one child at home and low educational level. The prevalence of short stature was higher in women (16.4% vs. 8.4%, p < 0.001) and was related with age, overweight and abdominal obesity.

Current mapping of obesity.

PubMed

Pérez Rodrigo, Carmen

2013-09-01

Obesity is a major risk factor for non-communicable diseases (NCDs), such as diabetes, cardiovascular diseases, and cancers. The worldwide prevalence of obesity has almost doubled between 1980 and 2008. In some regions, such as Europe, the Eastern Mediterranean and the Americas, more than 50% of women are overweight. Tonga, Nauru and the Cook Islands show the highest prevalence of obesity worldwide, above 60% in men and in women. China and the United States are the countries that experienced the largest absolute increase in the number of overweight and obese people between 1980 and 2008, followed by Brazil and Mexico. The regions with the largest increase in the prevalence of female obesity were Central Latin America, Oceania and Southern Latin America. Updated data provide evidence that the progression of the epidemic has effectively slowed for the past ten years in several countries. In low-income countries obesity is generally more prevalent among the better-off, while disadvantaged groups are increasingly affected as countries grow. Many studies have shown an overall socio-economic gradient in obesity in modern industrialized societies. Rates tend to decrease progressively with increasing socio-economic status. Children obesity rates in Spain are amongst the highest in the OECD. One in 3 children aged 13 to 14 are overweight. Overweight in infants and young children is observed in the upper middle-income countries. However, the fastest growth occurs in the group of lower middle-income countries. There is a growing body of evidence for an inverse association between SES and child obesity in developed countries. The prevalence of overweight and obesity is high in all age groups in many countries, but especially worrying in children and adolescents in developed countries and economies in transition. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

The Interactive Association of General Obesity and Central Obesity with Prevalent Hypertension in Rural Lanzhou, China

PubMed Central

Wang, Yuhong; Wan, Liping; Wang, Zengwu; Wang, Xin; Di, Zhaoxin; Liu, Xiaoyu

2016-01-01

Objective To evaluate the interactive association between obesity with different anthropometry indices and prevalence of hypertension in rural Lanzhou. Methods A cross-sectional survey was conducted in rural Lanzhou from April to July in 2013. The available information of 1275 rural residents aged more than 35 years was collected with a unified questionnaire and their blood pressure and anthropometry indices were measured in the field. The male-to-female ratio was 1:1.1. A generalized estimate equation (GEE) linear model was used to determine the association between obesity with different indexes and hypertension. Results There was a moderate prevalence of general obesity (~11%) and very high prevalence of central obesity (53.2~67%) among the adults of rural Lanzhou. The prevalence of hypertension approximated 28%. GEE linear models showed that obesity with any one of anthropometry indices was associated significantly with the increased prevalence of hypertension among both males and females. In females, general obesity increased the prevalence of hypertension by 37% (0.37, 95%CI: 0.27,0.47) but in males by 23% (0.23, 95%CI: 0.12,0.35). The hypertensive effect of all central obesity was much lower than that of general obesity but approximately comparable to that of overweight. In addition, the interactions of the classified body mass index (BMI) and central obesity showed that when general obesity or overweight coexisted with any one of central obesity, the prevalence of hypertension was increased significantly, and this effect was a little higher than the corresponding main effect of general obesity or overweight in females but was much higher in males. In addition, general obesity or overweight which did not coexist with central obesity was not significantly associated with the increased prevalence of hypertension, nor were the other situations of central obesity in the normal weight or underweight except for the situation of central obesity with waist

[Obesity and male infertility].

PubMed

Heráček, J; Sobotka, V; Urban, M

2012-10-01

The authors present a review on the effects of obesity on male fertility. Current scientific findings suggest an elevated risk of infertility among couples in which the male partner is obese. In obese men can be found reduced serum levels of androgens and SHBG and increased estrogen levels without compensatory increase in FSH. Among other impacts of male obesity that may contribute to increased risk of infertility are altered retention and metabolism of environmental toxins, lifestyle, sexual dysfunction, genetic factors, excessive secretion of hormones derived from adipose tissue, oxidative stress, sperm specific proteomic changes or elevated levels of cytokines. The increasing prevalence of obesity calls for greater clinical awareness of its impact on male fertility.

Hypercortisolism in obesity-associated hypertension.

PubMed

Varughese, Amy G; Nimkevych, Oksana; Uwaifo, Gabriel I

2014-07-01

Obesity is prevalent worldwide and associated with co-morbidities that result in increased cardiovascular risk. Hypertension is the most prevalent obesity comorbidity associated with increased cardiovascular risk. Obesity hypertension is a distinct subtype of essential hypertension. While endogenous Cushing's syndrome is an uncommon cause of both obesity and hypertension, the recent recognition of other hypercortisolemic states has raised the profile of hypercortisolism as an important contributor in obesity hypertension. The high prevalence of exogenous, iatrogenic, pseudo, and subclinical Cushing's syndromes makes hypercortisolism an important diagnostic consideration in the evaluation and management of patients with obesity hypertension who are resistant to conventional management. Available data suggest that the renin-angiotensin-aldosterone system modulating antihypertensives have the best efficacy in hypercortisolism-mediated obesity hypertension. Strategies aimed at reducing cortisol production and action also have utility. This review provides a comprehensive overview of the epidemiology, etiopathogenesis and management options available for glucocorticoid-mediated obesity hypertension.

Decreased Emotional Perception in Obesity.

PubMed

Giel, Katrin Elisabeth; Hartmann, Armin; Zeeck, Almut; Jux, Anna; Vuck, Alexander; Gierthmuehlen, Petra C Guess; Wetzler-Burmeister, Edda; Sandholz, Angelika; Marjanovic, Goran; Joos, Andreas

2016-07-01

There is hardly any empirical evidence on emotion processing by controlled studies in obesity. Participants rated their emotions in response to visual emotional stimuli from the International Affective Picture System. Study 1 compared obese women with normal-weight controls and women with eating disorders. Study 2 compared obese men with normal-weight controls. Obese women had reduced emotional intensity scores for all basic emotions and the mixed emotion sadness-fear. Obese men had reduced scores for all emotions except happiness and disgust; anger showed a trend towards significance. The results were mainly based on ratings from non-depressed obese individuals. Obese men and women scored significantly lower on most basic and mixed emotions. Non-depressed obese subjects seem particularly affected. These new findings must be validated by further study, and longitudinal evaluation after weight loss, e.g. by bariatric surgery, will be of interest. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Blood-Brain Barriers in Obesity.

PubMed

Rhea, Elizabeth M; Salameh, Therese S; Logsdon, Aric F; Hanson, Angela J; Erickson, Michelle A; Banks, William A

2017-07-01

After decades of rapid increase, the rate of obesity in adults in the USA is beginning to slow and the rate of childhood obesity is stabilizing. Despite these improvements, the obesity epidemic continues to be a major health and financial burden. Obesity is associated with serious negative health outcomes such as cardiovascular disease, type II diabetes, and, more recently, cognitive decline and various neurodegenerative dementias such as Alzheimer's disease. In the past decade, major advancements have contributed to the understanding of the role of the central nervous system (CNS) in the development of obesity and how peripheral hormonal signals modulate CNS regulation of energy homeostasis. In this article, we address how obesity affects the structure and function of the blood-brain barrier (BBB), the impact of obesity on Alzheimer's disease, the effects of obesity on circulating proteins and their transport into the brain, and how these changes can potentially be reversed by weight loss.

Energy metabolism in human obesity.

PubMed

Jéquier, E

1989-01-01

Obesity results from a chronic imbalance between energy intake and expenditure. Accurate measurements of total energy expenditure of lean and obese individuals with a respiration chamber have clearly shown that obese individuals expand more energy than lean sedentary subjects. Studies on the body composition of obese individuals reveal that not only the fat mass is enlarged, but the fat-free mass is also increased as compared with that of lean subjects. Since basal metabolic rate is proportional to the fat-free mass, obese subjects have a greater basal metabolic rate than lean controls. The energy cost of weight bearing activities such as walking and standing is related to body weight, and is therefore increased in obese individuals. The thermogenic response to food ingestion, the diet-induced thermogenesis, has been found to be reduced in some groups of obese people, but not in all obese individuals. The thermic effect of glucose or to meal ingestion is blunted in obese subjects with insulin resistance. Any alteration in thermogenic responses to a caloric excess can be important to store or to oxidize part of the excessive energy intake. After weight reduction in obese subjects due to a hypocaloric diet, the total 24-hour energy expenditure decreases by 20 to 25 kcal/day for each kilogram of weight loss. Failure to adapt the every day energy intake accordingly will result in body weight gain and relapse of obesity.

Prevalence of Overweight, Obesity, and Abdominal Obesity among Urban Saudi Adolescents: Gender and Regional Variations

PubMed Central

Abahussain, Nada A.; Al-Sobayel, Hana I.; Qahwaji, Dina M.; Alsulaiman, Nouf A.; Musaiger, Abdulrahman O.

2014-01-01

ABSTRACT The nutrition transition with associated lifestyle-related non-communicable diseases has rapidly reached many developing countries, including Saudi Arabia. Therefore, the objective of this study was to examine the prevalence of overweight, obesity, and abdominal obesity among Saudi adolescents. This school-based multicentre cross-sectional study was conducted during 2009-2010 in three major cities in Saudi Arabia: Al-Khobar, Jeddah, and Riyadh. Participants included 2,908 students of secondary schools (1,401 males and 1,507 females) aged 14 to 19 years, randomly selected using a multistage stratified cluster-sampling technique. Weight, height, and waist-circumference were measured; prevalence of overweight and obesity was determined using age- and sex-specific BMI cutoff reference standards of the International Obesity Task Force (IOTF). Abdominal obesity was determined using waist-to-height ratio (WHtR) cutoffs (above 0.5). The prevalence of overweight was 19.5% in males and 20.8% in females while that of obesity was 24.1% in males and 14% in females. The prevalence of abdominal obesity in males and females was 35.9% and 30.3% respectively. Higher prevalence of obesity was observed among adolescents in private schools. Across all ages, overweight and obesity ranged from 39.9% to 45.6% in males and from 30.4% to 38.7% in females. ANCOVA, controlling for age, showed significant interaction effects (city by gender). It is concluded that the proportions of overweight, obesity, and abdominal obesity, observed among Saudi adolescents were remarkably high. Such high prevalence of overweight and obesity is a major public-health concern. PMID:25895197

of obese Turkish female patients

PubMed

Özşahin, Akatlı Kürşad; Altıntaş, Ebru

2018-04-30

Background/aim: Mental disorders may accompany obesity. This study aims to evaluate the association between social anxiety disorder (SAD) and obesity and the risk factors for SAD in obese female patients. Materials and methods: A total of 114 obese patients and 110 healthy controls were included. The Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), State and Trait Anxiety Inventory (STAI I-II), and Liebowitz Social Anxiety Scale (LSAS) were administered to assess anxiety, depression, and social anxiety levels. Scale scores were analyzed statistically. Results: The rate of SAD in obese female patients was found to be 8.8%. Anxiety, depression, and social anxiety levels were significantly higher in the obesity group compared to the control group (P < 0.05). According to linear regression analyses, a significant association between LSAS anxiety level and age, prior surgery, social support, history of being teased, BDI, and BAI was found. Conclusion: The present study shows that many factors are related to obesity and SAD in obese female patients. The clinical implications of these findings should be considered. Interventions for these factors may help prevent SAD in obese female patients.

Obesity among Women in Turkey.

PubMed

Santas, Fatih; Santas, Gulcan

2018-05-01

This study aimed to determine the prevalence and potential risk factors of obesity among women in Turkey. The data source was the Turkey Demographic and Health Survey (TDHS) in 1998, 2003, 2008 and 2013, conducted by Hacettepe University Institute of Population Studies. Cross-tables and binary logistic regression were used in the study. Obesity was a serious problem among women in Turkey. Obesity rate was 21.7% in 1998 and increased to 26.5% in 2013. Age, education level, the number of births, region, residence, and wealth status were included as potential risk factors. Age was an important variable affecting obesity and increased with age. There was an inverse relationship between obesity and education level. Women having no education or not completed primary school and those who were not working were higher at obesity risk. Obesity increased with the giving births of mothers. Obesity was mostly observed in the West and Central. As household welfare increased, obesity increased except for 2013 research. Preventive interventions should be announced particularly among urban women in Turkey. Women should be stimulated by physical activities and informed by realistic food policies.

Meta-review of protein network regulating obesity between validated obesity candidate genes in the white adipose tissue of high-fat diet-induced obese C57BL/6J mice.

PubMed

Kim, Eunjung; Kim, Eun Jung; Seo, Seung-Won; Hur, Cheol-Goo; McGregor, Robin A; Choi, Myung-Sook

2014-01-01

Worldwide obesity and related comorbidities are increasing, but identifying new therapeutic targets remains a challenge. A plethora of microarray studies in diet-induced obesity models has provided large datasets of obesity associated genes. In this review, we describe an approach to examine the underlying molecular network regulating obesity, and we discuss interactions between obesity candidate genes. We conducted network analysis on functional protein-protein interactions associated with 25 obesity candidate genes identified in a literature-driven approach based on published microarray studies of diet-induced obesity. The obesity candidate genes were closely associated with lipid metabolism and inflammation. Peroxisome proliferator activated receptor gamma (Pparg) appeared to be a core obesity gene, and obesity candidate genes were highly interconnected, suggesting a coordinately regulated molecular network in adipose tissue. In conclusion, the current network analysis approach may help elucidate the underlying molecular network regulating obesity and identify anti-obesity targets for therapeutic intervention.

Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents.

PubMed

Liang, J; Matheson, B E; Kaye, W H; Boutelle, K N

2014-04-01

Childhood obesity rates have risen dramatically over the past few decades. Although obesity has been linked to poorer neurocognitive functioning in adults, much less is known about this relationship in children and adolescents. Therefore, we conducted a systematic review to examine the relationship between obesity and obesity-related behaviors with neurocognitive functioning in youth. We reviewed articles from 1976 to 2013 using PsycInfo, PubMed, Medline and Google Scholar. Search terms included cognitive function, neurocognitive function/performance, executive function, impulsivity, self-regulation, effortful control, cognitive control, inhibition, delayed gratification, memory, attention, language, motor, visuo-spatial, academic achievement, obesity, overweight, body mass index, waist-hip ratio, adiposity and body fat. Articles were excluded if participants had health problems known to affect cognitive functioning, the study used imaging as the only outcome measure, they were non-peer-reviewed dissertations, theses, review papers, commentaries, or they were non-English articles. Sixty-seven studies met inclusion criteria for this review. Overall, we found data that support a negative relationship between obesity and various aspects of neurocognitive functioning, such as executive functioning, attention, visuo-spatial performance, and motor skill. The existing literature is mixed on the effects among obesity, general cognitive functioning, language, learning, memory, and academic achievement. Executive dysfunction is associated with obesity-related behaviors, such as increased intake, disinhibited eating, and less physical activity. Physical activity is positively linked with motor skill. More longitudinal research is needed to determine the directionality of such relationships, to point towards crucial intervention time periods in the development of children, and to inform effective treatment programs.

Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents

PubMed Central

Liang, J.; Matheson, BE.; Kaye, WH.; Boutelle, KN.

2015-01-01

Childhood obesity rates have risen dramatically over the past few decades. Although obesity has been linked to poorer neurocognitive functioning in adults, much less is known about this relationship in children and adolescents. Therefore, we conducted a systematic review to examine the relationship between obesity and obesity-related behaviors with neurocognitive functioning in youth. We reviewed articles from 1976 to 2013 using PsycInfo, PubMed, Medline and Google Scholar. Search terms included cognitive function, neurocognitive function/performance, executive function, impulsivity, self-regulation, effortful control, cognitive control, inhibition, delayed gratification, memory, attention, language, motor, visuo-spatial, academic achievement, obesity, overweight, body mass index, waist-hip ratio, adiposity and body fat. Articles were excluded if participants had health problems known to affect cognitive functioning, the study used imaging as the only outcome measure, they were non-peer-reviewed dissertations, theses, review papers, commentaries, or they were non-English articles. Sixty-seven studies met inclusion criteria for this review. Overall, we found data that support a negative relationship between obesity and various aspects of neurocognitive functioning, such as executive functioning, attention, visuo-spatial performance, and motor skill. The existing literature is mixed on the effects among obesity, general cognitive functioning, language, learning, memory, and academic achievement. Executive dysfunction is associated with obesity-related behaviors, such as increased intake, disinhibited eating, and less physical activity. Physical activity is positively linked with motor skill. More longitudinal research is needed to determine the directionality of such relationships, to point towards crucial intervention time periods in the development of children, and to inform effective treatment programs. PMID:23913029

Assessing and counseling the obese patient: Improving resident obesity counseling competence.

PubMed

Iyer, Shwetha; Jay, Melanie; Southern, William; Schlair, Sheira

To evaluate obesity counseling competence among residents in a primary care training program METHODS: We delivered a 3h obesity curriculum to 28 Primary Care residents and administered a pre-curriculum and post curriculum survey looking specifically at self-assessed obesity counseling competence. Nineteen residents completed both the pre curriculum survey and the post curriculum survey. The curriculum had a positive impact on residents' ability to ascertain patient's stage of change, use different methods to obtain diet history (including 24h recall, food record or food frequency questionnaire), respond to patient's questions regarding treatment options, assist patients in setting realistic goals for weight loss based on making permanent lifestyle changes, and use of motivational interviewing to change behavior. When looking at the 5As domains, there was a significant improvement in the domains of Assess, Advise, and Assist. The proportion of residents with a lower level of self-assessed obesity counseling competence reduced from 75% before the curriculum to 37.5% (p=0.04) after the curriculum. Our curriculum addressing weight loss counseling using the 5As model increased obesity counseling competence among residents in a primary care internal medicine residency program. Copyright © 2018 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Association between overweight and obesity in schoolchildren with rs9939609 polymorphism (FTO) and family history for obesity.

PubMed

Reuter, Cézane Priscila; Burgos, Miria Suzana; Bernhard, Joana Carolina; Tornquist, Debora; Klinger, Elisa Inês; Borges, Tássia Silvana; Renner, Jane Dagmar Pollo; de Moura Valim, Andréia Rosane; de Mello, Elza Daniel

2016-01-01

To determine the association between overweight/obesity in schoolchildren with FTO rs9939609 polymorphism (fatmass and obesity associated) and family history of obesity. Cross-sectional study comprising a sample of 406 children aged 7-17 years in a city in southern Brazil. Overweight/obesity in schoolchildren was assessed by body mass index (BMI), and family history of obesity was self-reported by parents. Polymorphism genotyping was performed by real time PCR (polymerase chain reaction). The association between the nutritional status of schoolchildren with the presence of family obesity, stratified by polymorphism genotypes (AA [at-risk for obesity], AT, and TT), was assessed by prevalence ratio values (PR) through Poisson regression. Among schoolchildren with the AA genotype, 57.4% had overweight/obesity; the percentage was lower for the AT and TT genotypes (33.1% and 28.9%, respectively). Overweight/obesity in schoolchildren was associated with a family history of obesity, especially among children with the AA genotype. The prevalence was higher among those with an obese mother (PR: 1.28; p<0.001), obese maternal or paternal grandmother (PR: 1.22; p=0.047), and obese paternal grandfather (PR: 1.32; p<0.001). There is an association between the AA genotype of rs9939609 polymorphism and BMI among schoolchildren. The association between overweight/obesity in schoolchildren with a family history of obesity was found mainly among students with the AA genotype. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Obesity bias among health and non-health students attending an Australian university and their perceived obesity education.

PubMed

Robinson, Emma L; Ball, Lauren E; Leveritt, Michael D

2014-01-01

This study compared the level of prejudice against obese individuals (obesity bias) among final-year health and non-health students, and associated obesity education. Cross-sectional online survey of 479 final-year students (292 health and 187 non-health) from Griffith University, Australia. Implicit and explicit obesity bias was measured using validated tools, and perceived obesity education ranked from "none" to "excellent." Data were analyzed quantitatively using analysis of variance and independent sample t tests. Statistical significance was set at P < .05. Students' mean age was 26.2 ± 7.6 years and body mass index was 23.2 ± 4.7 kg/m(2). Health and non-health students exhibited significant levels of obesity bias. Non-health students were more likely to suggest that obese individuals lacked willpower (P = .03). Students' self-reported obesity education varied considerably. Those who reported a higher level of genetics-related obesity education were less likely to believe that obese individuals were "bad" (P = .002) or to show concern about putting on weight (P = .01). Obesity bias exists in health students in Australia and is similar to non-health students' obesity bias levels. Students' self-reported genetics-related obesity education may be associated with obesity bias. Modifications to existing health curricula should be considered to reduce obesity bias among future health professionals. Copyright © 2014 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Childhood obesity and self-esteem.

PubMed

Strauss, R S

2000-01-01

Although childhood obesity may have detrimental consequences for childhood self-esteem, the prevalence and magnitude of this problem is controversial. In addition, the social and emotional effects of decreased self-esteem in obese children are unknown. A total of 1520 children, 9 to 10 years of age, born to mothers in the National Longitudinal Survey of Youth were studied. Comprehensive demographic data including race and family income were available in 97% of the cohort. Self-esteem was measured using Self-Perception Profile for Children. The 4-year follow-up Self-Perception Profile for Children scores were available in 79% of the children. Obesity was defined as a body mass index greater than the 95th percentile for age and gender. Additional data include a self-administered questionnaire at 13 to 14 years of age concerning emotional well being, smoking, and alcohol consumption. Data were stratified by race and gender. The data were weighted to reflect a nationally representative sample of children born to mothers 17 to 28 years of age. Scholastic and global self-esteem scores were not significantly different among 9- to 10-year-old obese and nonobese children. However, over the 4-year period, obese Hispanic females and obese white females showed significantly decreased levels of global self-esteem compared with nonobese Hispanic females and nonobese white females, respectively. Mild decreases in self-esteem also were observed in obese boys compared with nonobese boys. As a result, by 13 to 14 years of age, significantly lower levels of self-esteem were observed in obese boys, obese Hispanic girls, and obese white girls compared with their nonobese counterparts. Decreasing levels of self-esteem in obese children were associated with significantly increased rates of sadness, loneliness, and nervousness compared with obese children whose self-esteem increased or remained unchanged. In addition, obese children with decreasing levels of self-esteem over the 4-year

Obesity and Headache: Part I – A Systematic Review of the Epidemiology of Obesity and Headache

PubMed Central

Chai, Nu Cindy; Scher, Ann I.; Moghekar, Abhay; Bond, Dale S.; Peterlin, B. Lee

2014-01-01

Individually, both obesity and headache are conditions associated with a substantial personal and societal impact. Recent data support that obesity is comorbid with headache in general and migraine specifically, as well as with certain secondary headache conditions such as idiopathic intracranial hypertension. In the current manuscript, we first briefly review the epidemiology of obesity and common primary and secondary headache disorders individually. This is followed by a systematic review of the general population data evaluating the association between obesity and headache in general, and then obesity and migraine and tension-type headache disorders. Finally, we briefly discuss the data on the association between obesity and a common secondary headache disorder that is associated with obesity, idiopathic intracranial hypertension. Taken together, these data suggest that it is important for clinicians and patients to be aware of the headache/migraine-obesity association, given that it is potentially modifiable. Hypotheses for mechanisms of the obesity-migraine association and treatment considerations for overweight and obese headache sufferers are discussed in the companion manuscript, as part II of this topic. PMID:24512574

Obesity Prevention in the Nordic Countries.

PubMed

Stockmarr, Anders; Hejgaard, Tatjana; Matthiessen, Jeppe

2016-06-01

Previous studies have shown that mean BMI and prevalences of overweight/obesity and obesity have increased over the last decades in the Nordic countries, despite highly regulated societies with a focus on obesity prevention. We review recent overweight/obesity and obesity prevention initiatives within four of the five Nordic countries: Sweden, Denmark, Finland, and Iceland. Moreover, we analyze the current situation based on monitoring data on BMI collected in 2011 and 2014, and obtain overall estimates of overweight/obesity and obesity prevalences for the Nordic Region. Data analysis shows that obesity in adults has increased from 2011 to 2014, while no significant changes were found for children. No significant increases were found for mean BMI and overweight/obesity prevalence. Obesity prevention initiatives among the Nordic countries are highly similar although minor differences are present, which is rooted in transnational Nordic cooperation and comparable societal structures.

7th to 9th grade obese adolescents' perceptions about obesity in Tamaulipas, Mexico.

PubMed

de la Luz Martínez-Aguilar, Ma; Flores-Peña, Yolanda; de las Mercedes Rizo-Baeza, Ma; Aguilar-Hernández, Rosa Ma; Vázquez-Galindo, Laura; Gutiérres-Sánchez, Gustavo

2010-01-01

The objective was to explore obese adolescents perceptions about obesity among students in the seventh to ninth grade of a public school in Tamaulipas, Mexico. This is a qualitative study. Participants were 24 adolescents with a body mass index equal to or greater than the 95th percentile. Semistructured interviews were conducted until data saturation was reached and the meaning was understood. The adolescents defined obesity according to standards of measurement. They identified the hereditary factor as the main obesity cause, tended to underestimate obesity and had low self-esteem. They reported problems to do physical exercise and get clothes in order to improve their image, and feel rejected by their peers in school. It was identified that these adolescents have psychological defense mechanisms against obesity and that some of them are making efforts to lose weight. Obesity entails social and psychological health implications for persons suffering from this problem. Interventions should be put in practice.