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Sample records for 30-day-old obese zucker

  1. Increased in vivo glucose utilization in 30-day-old obese Zucker rat: Role of white adipose tissue

    SciTech Connect

    Krief, S.; Bazin, R.; Dupuy, F.; Lavau, M. )

    1988-03-01

    In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by (3-{sup 3}H)glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia. In obese compared with lean rats, tissue glucose uptake was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart in proximal intestine, and in total muscular mass of limbs. The data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake.

  2. Renal Function and Hemodynamic Study in Obese Zucker Rats

    PubMed Central

    Park, Sung Kwang; Kang, Sung Kyew

    1995-01-01

    Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies were performed in these rats. Results Functional studies showed that obese Zucker rats exhibited increases in kidney weight and GFR(obese Zucker, 1.23±.07)ml/min; lean Zucker, 0.93±.03ml/min). Micropuncture studies revealed that the increase in GFR in obese Zucker rats was attributable to the increases in the single nephron plasma flow rate and glomerular transcapillary hydraulic pressure. The glomerular ultrafiltration coefficient was the same in both groups. Morphologic studies revealed that the increase in GFR in obese Zucker rats was associated with an increase in glomerular volume. Conclusions These results suggest that obesity and hyperinsulinemia, which are the characteristics of type II diabetes, can be associated with glomerular hyperfiltration and glomerular capillary hypertension. PMID:7626557

  3. Obesity decreases serum selenium levels in DMBA-induced mammary tumor using Obese Zucker Rat Model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, we reported that obese Zucker rats had increased susceptibility to DMBA-induced mammary tumors compared to lean Zucker rats. Several studies suggest that lower serum selenium may play an important role in increasing the risk of several types of cancers (e.g, colon, breast and prostate canc...

  4. Amino acid uptake by liver of genetically obese Zucker rats.

    PubMed Central

    Ruiz, B; Felipe, A; Casado, J; Pastor-Anglada, M

    1991-01-01

    Alanine and glutamine uptake by the liver of 50-52-day-old genetically obese Zucker rats and their lean littermates has been studied. The net uptake in vivo of L-alanine is 2-fold higher in the obese animals. No significant change in L-glutamine net balance was found. We also studied the Na(+)-dependent uptake of L-alanine and L-glutamine into plasma-membrane vesicles isolated from either obese- or lean-rat livers. Vmax. values of both L-alanine and L-glutamine transport were 2-fold higher in those preparations from obese rats. No change in Km was observed. As suggested by inhibition studies, this seemed to be mediated by an enhancement of the activities of systems A, ASC and N. We conclude that the liver of the obese Zucker rat is extremely efficient in taking up neutral amino acids from the afferent blood, which results in an enhanced net uptake of L-alanine in vivo. The changes in transport activities at the plasma-membrane level might contribute to increase amino acid disposal by liver, probably for lipogenic purposes, as recently reported by Terrettaz & Jeanrenaud [Biochem. J. (1990) 270, 803-807]. PMID:1684102

  5. Comparison of tissue metal concentrations in Zucker lean, Zucker obese, and Zucker diabetic fatty rats and the effects of chromium supplementation on tissue metal concentrations.

    PubMed

    Staniek, Halina; Rhodes, Nicholas R; Di Bona, Kristin R; Deng, Ge; Love, Sharifa T; Pledger, Leigh Ann; Blount, Jeremy; Gomberg, Emmalea; Grappe, Frances; Cernosek, Chelsea; Peoples, Brittany; Rasco, Jane F; Krejpcio, Zbigniew; Vincent, John B

    2013-03-01

    Diabetes results in several metabolic changes, including alterations in the transport, distribution, excretion, and accumulation of metals. While changes have been examined in several rat models of insulin resistance and diabetes, the metal ion concentrations in the tissues of Zucker lean, Zucker obese (an insulin resistance and early stage diabetes model), and Zucker diabetic fatty (ZDF, a type 2 diabetes model) have not previously been examined in detail. The concentration of Cu, Zn, Fe, Mg, and Ca were examined in the liver, kidney, heart and spleen, and Cr concentration in the liver and kidney of these rats were examined. Zucker obese rats have a reduction in the concentration of Cu, Zn, Fe, Mg in the liver compared to ZDF and/or lean Zucker rats, presumably as a result of the increased fat content of the liver of the obese rats. ZDF rats have increased concentrations of kidney Cu compared to the lean rats, while kidney Ca concentrations are increased in the Zucker obese rats. Spleen Fe concentrations are decreased in Zucker obese rats compared to the lean rats. No effects on metal concentrations in the heart were observed between the lean, obese, and ZDF rats, and no effects on Cr concentrations were identified. Cr(III) complexes have previously been shown to have beneficial effects on the signs of insulin resistance in Zucker obese and ZDF rats. The effects of daily gavage administration of chromium picolinate ([Cr(pic)(3)]) (1 mg Cr/kg body mass), CrCl(3) (1 mg Cr/kg body mass), and Cr3 ([Cr(3)O(propionate)(6)(H(2)O)(3)](+)) (33 μg and 1 mg Cr/kg body mass) on metal concentrations in these tissues were examined. Treatment with CrCl(3) and Cr3, but not [Cr(pic)(3)], at 1 mg Cr/kg resulted in a statistically significant accumulation of Cr in the kidney of lean and obese but not ZDF rats but resulted in lowering the elevated levels of kidney Cu in ZDF rats, suggesting a beneficial effect on this symptom of type 2 diabetes.

  6. Elevation of circulating LOX-1 ligand levels in Zucker obese and diabetic rats.

    PubMed

    Wakabayashi, Ichiro; Shimomura, Tomoko; Nakanishi, Mamoru; Uchida, Kagehiro

    2015-01-01

    LOX-1 ligands containing apolipoprotein B (LAB) reflect ligand activity of LOX-1, which is a key molecule for initiation of atherosclerosis. The Zucker rat is a well-known model used for research on obesity and diabetes. Blood levels of LAB were compared among Zucker fatty (ZF), Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. Log-transformed LAB was significantly higher in ZF and ZDF rats than in control ZL rats, while no significant difference was found in log-transformed LAB of ZF and ZDF rats. This study for the first time demonstrated that circulating LOX-1 ligands were elevated in obesity and diabetes model rats.

  7. Tongue Fat Infiltration in Obese Versus Lean Zucker Rats

    PubMed Central

    Brennick, Michael J.; Delikatny, James; Pack, Allan I.; Pickup, Stephen; Shinde, Sarika; Zhu, Jing-Xu; Roscoe, Ivana; Kim, David Y.; Buxbaum, Laurence U.; Cater, Jacqueline R.; Schwab, Richard J.

    2014-01-01

    Study Objectives: Obesity is the most important risk factor for obstructive sleep apnea (OSA), and the effects of obesity may be mediated by tongue fat. Our objective was to examine the effects of obesity on upper airway structures in obese (OBZ) and non-obese (NBZ) Zucker rats. Design: Animal study. Setting: Academic Medical Center. Participants: OBZ (638.2 ± 39 g; 14.9 ± 1.1 w) and age-matched NBZ Zucker (442.6 ± 37 g, 15.1 ± 1.5 w) rats. Interventions: Tongue fat and volume and were assessed using: in vivo magnetic resonance spectroscopy (MRS), magnetic resonance imaging including Dixon imaging for tongue fat volume, ex vivo biochemistry (fat quantification; triglyceride (mg)/tissue (g), and histology (Oil Red O stain). Measurements and Results: MRS: overall OBZ tongue fat/water ratio was 2.9 times greater than NBZ (P < 0.002) with the anterior OBZ tongue up to 3.3 times greater than NBZ (P < 0.002). Biochemistry: Triglyceride (TG) in the tongue was 4.4 times greater in OBZ versus NBZ (P < 0.0006). TG was greater in OBZ tongue (3.57 ± 1.7 mg/g) than OBZ masseter muscle (0.28 ± 0.1; P < 0.0001) but tongue and masseter TG were not different in NBZ rats (0.82 ± 0.3 versus 0.28 ± 0.1 mg/g, P = 0.67). Dixon fat volume was significantly increased in OBZ (56 ± 15 mm3) versus NBZ (34 ± 5 mm3, P < 0.004). Histology demonstrated a greater degree of intracellular muscle fat and extramuscular fat infiltration in OBZ versus NBZ rats. Conclusions: Genetically obese rats had a large degree of fat infiltration in the tongue compared to both skeletal muscle and tongue tissues of the non-obese age-matched littermates. The significant fat increase and sequestration in the obese tongue may play a role in altered tongue neuromuscular function, tongue stiffness or metabolic function. Citation: Brennick MJ, Delikatny J, Pack AI, Pickup S, Shinde S, Zhu JX, Roscoe I, Kim DY, Buxbaum LU, Cater JR, Schwab RJ. Tongue fat infiltration in obese versus lean Zucker rats. SLEEP 2014

  8. PROGRESSIVE RENAL VASCULAR PROLIFERATION AND INJURY IN OBESE ZUCKER RATS

    PubMed Central

    Iliescu, Radu; Chade, Alejandro R.

    2010-01-01

    Objective Obesity, an independent risk factor for chronic kidney disease, may induce renal injury by promoting inflammation. Inflammatory cytokines can induce neovascularization in different organs, including the kidneys. However, whether obesity triggers renal neovascularization and, if so, its effect on renal function has never been investigated. Methods Blood pressure, proteinuria and glomerular-filtration-rate (GFR) were measured in-vivo. Renal microvascular (MV) architecture was studied by 3D micro-CT in lean and obese Zucker rats (LZR and OZR, n=7/group) at 12, 22, and 32 weeks of age. Renal inflammation was assessed by quantifying interleukin (IL)-6, tumor-necrosis-factor (TNF)-alpha, and ED-1 expression, as renal fibrosis in trichrome-stained cross-sections. Results Mild inflammation and lower GFR was only observed in younger OZR, without renal fibrosis or changes in MV density. Interestingly, renal MV density increased in OZR at 32 weeks of age, accompanied by pronounced increase in renal IL-6 and TNF-alpha, ED-1+ cells, proteinuria, decreased GFR, and fibrosis. Conclusion This study shows increased renal cortical vascularization in experimental obesity, suggesting neovascularization as an evolving process as obesity progresses. Increased renal vascularization, possibly triggered by inflammation, may reflect an initially compensatory mechanism in obesity. However, increased inflammation and inflammatory-induced neovascularization may further promote renal injury as obesity advances. PMID:20536738

  9. Pepsin egg white hydrolysate modulates gut microbiota in Zucker obese rats.

    PubMed

    Requena, Teresa; Miguel, Marta; Garcés-Rimón, Marta; Martínez-Cuesta, M Carmen; López-Fandiño, Rosina; Peláez, Carmen

    2017-01-25

    There is limited information that relates the intake of food-derived bioactive peptides and the gut microbiota. We have previously described a pepsin hydrolysate of egg white (EWH) that ameliorates fat accumulation and dyslipidemia, while reducing oxidative stress and inflammation markers in obese Zucker rats. The aim of this study was to associate the beneficial effects of EWH with gut microbiota changes in these animals. Obese Zucker rats received daily 750 mg kg(-1) EWH in drinking water for 12 weeks and faeces were analysed for microbial composition and metabolic compounds in comparison with Zucker lean rats and obese controls. EWH supplementation modulated the microbiological characteristics of the obese rats to values similar to those of the lean rats. Specifically, counts of total bacteria, Lactobacillus/Enterococcus and Clostridium leptum in EWH fed obese Zucker rats were more similar to the lean rats than to the obese controls. Besides, feeding the obese Zucker rats with EWH reduced (P < 0.05) the faecal concentration of lactic acid. The physiological benefits of EWH in the improvement of obesity associated complications of Zucker rats could be associated with a more lean-like gut microbiota and a tendency to diminish total short-chain fatty acids (SCFA) production and associated obesity complications. The results warrant the use of pepsin egg white hydrolysate as a bioactive food ingredient.

  10. Improved functional vasodilation in obese Zucker rats following exercise training.

    PubMed

    Sebai, Mohamad; Lu, Silu; Xiang, Lusha; Hester, Robert L

    2011-09-01

    Obese individuals exhibit impaired functional vasodilation and exercise performance. We have demonstrated in obese Zucker rats (OZ), a model of morbid obesity, that insulin resistance impairs functional vasodilation via an increased thromboxane receptor (TP)-mediated vasoconstriction. Chronic treadmill exercise training improves functional vasodilation in the spinotrapezius muscle of the OZ, but the mechanisms responsible for the improvement in functional vasodilation are not clear. Based on evidence that exercise training improves insulin resistance, we hypothesized that, in the OZ, exercise training increases functional vasodilation and exercise capability due to decreases TP-mediated vasoconstriction associated with improved insulin sensitivity. Six-week-old lean Zucker rats (LZ) and OZ were exercised on a treadmill (24 m/min, 30 min/day, 5 days/wk) for 6 wk. An oral glucose tolerance test was performed at the end of the training period. We measured functional vasodilation in both exercise trained (spinotrapezius) and nonexercise trained (cremaster) muscles to determine whether the improved functional vasodilation following exercise training in OZ is due to a systemic improved insulin resistance. Compared with LZ, the sedentary OZ exhibited impairments in glucose tolerance and functional vasodilation in both muscles. The TP antagonist SQ-29548 improved the vasodilator responses in the sedentary OZ with no effect in the LZ. Exercising training of the LZ increased the functional vasodilation in spinotrapezius muscle, with no effect in the cremaster muscle. Exercising training of the OZ improved glucose tolerance, along with increased functional vasodilation, in both the spinotrapezius and cremaster muscles. SQ-29548 treatment had no effect on the vasodilator responses in either cremaster or spinotrapezius muscles of the exercise-trained OZ. These results suggest that, in the OZ, there is a global effect of exercising training to improve insulin resistance and

  11. Cardiovascular effects of captopril and enalapril in obese Zucker rats.

    PubMed

    Duarte, J; Martinez, A; Bermejo, A; Vera, B; Gámez, M J; Cabo, P; Zarzuelo, A

    1999-01-22

    The effects of two weeks of oral administration of the angiotensin-converting enzyme inhibitors captopril (a sulphydryl-containing drug) and enalapril (which lacks the sulphydryl group) on skeletal muscle glucose uptake, arterial blood pressure, cardiac hypertrophy, proteinuria and aortic vascular reactivity in obese Zucker rats were evaluated. Captopril (50 mg kg(-1) once daily) and enalapril (10 mg kg(-1) did not modify body weight gain or food or water intake. Both drugs decreased systolic blood pressure (157+/-6, 133+/-4 and 136+/-3 mm Hg, in vehicle-, captopril- and enalapril-treated rats, respectively), blood glucose (172+/-8 vs. 151+/-7 and 158+/-5 mg dl(-1), respectively), proteinuria (46+/-10 vs. 17+/-2 and 18+/-2.5 mg dl(-1), respectively) and heart weight (2.17+/-0.03, 1.98+/-0.02 and 1.99+/-0.04 mg g(-1)of body weight, respectively). Plasma insulin concentration was significantly increased by enalapril (17+/-2 ng ml(-1) vs. 9+/-2) but not by captopril (12+/-1). In the absence of insulin, the diaphragms from captopril- or enalapril-treated rats showed a significantly higher glucose uptake than that of controls (31% and 30% vs. control group, respectively). The presence of insulin in the incubation medium did not stimulate peripheral glucose uptake in the control group but significantly increased glucose uptake in diaphragms from captopril- or enalapril-treated rats (enhancement of glucose uptake vs. control: 52% and 43%, respectively). Endothelium-intact aortic rings from control Zucker rats showed a poor relaxant response to acetylcholine (maximal relaxation of 38.4+/-4.7%). Captopril significantly improved the endothelium-dependent vascular relaxation responses to acetylcholine and the endothelium-independent relaxation to the nitric oxide donor sodium nitroprusside whereas enalapril did not modify these relaxant responses. Neither captopril nor enalapril significantly affected the vascular contractile responses to the vasoconstrictors noradrenaline or

  12. Obese and lean Zucker rats respond similarly to intraperitoneal administration of gastrin-releasing peptides.

    PubMed

    Washington, Martha C; Park, Karen H; Sayegh, Ayman I

    2014-08-01

    The Zucker rat is an animal model used to study obesity and the control of food intake by various satiety peptides. The amphibian peptide bombesin (Bn) reduces cumulative food intake similarly in both obese and lean weanling Zucker rats. Here, we hypothesized that intraperitoneal (i.p) administration of gastrin-releasing peptides-10, -27 and -29 (GRP-10, GRP-27, GRP-29), which are the mammalian forms of Bn, would reduce first meal size (MS, 10% sucrose) and prolong the intermeal interval (IMI, time between first and second meals) similarly in obese and lean adult Zucker rats. To test this hypothesis, we administered GRP-10, GRP-27 and GRP-29 (0, 2.1, 4.1 and 10.3 nmol/kg) i.p. to obese and lean male Zucker rats (who were deprived of overnight food but not water) and then measured the first and second MS, IMI and satiety ratio (SR, IMI/MS). We found that in both obese and lean rats, all forms of GRP reduced the first MS, and in lean rats, they also decreased the second MS. Additionally, GRP-10 and GRP-29 prolonged the IMI in both obese and lean rats, but GRP-27 only prolonged it in lean rats. Finally, we found that all forms of GRP increased the SR in both obese and lean rats. In agreement with our hypothesis, we conclude that all forms of GRP reduce food intake in obese and lean adult Zucker rats similar to Bn in weanling rats.

  13. Circadian rhythms of temperature and activity in obese and lean Zucker rats

    NASA Technical Reports Server (NTRS)

    Murakami, D. M.; Horwitz, B. A.; Fuller, C. A.

    1995-01-01

    The circadian timing system is important in the regulation of feeding and metabolism, both of which are aberrant in the obese Zucker rat. This study tested the hypothesis that these abnormalities involve a deficit in circadian regulation by examining the circadian rhythms of body temperature and activity in lean and obese Zucker rats exposed to normal light-dark cycles, constant light, and constant dark. Significant deficits in both daily mean and circadian amplitude of temperature and activity were found in obese Zucker female rats relative to lean controls in all lighting conditions. However, the circadian period of obese Zucker rats did not exhibit differences relative to lean controls in either of the constant lighting conditions. These results indicate that although the circadian regulation of temperature and activity in obese Zucker female rats is in fact depressed, obese rats do exhibit normal entrainment and pacemaker functions in the circadian timing system. The results suggest a deficit in the process that generates the amplitude of the circadian rhythm.

  14. Cyclooxygenase-2 Inhibition Restored Endothelium-Mediated Relaxation in Old Obese Zucker Rat Mesenteric Arteries

    PubMed Central

    Vessières, Emilie; Belin de Chantemèle, Eric J.; Toutain, Bertrand; Guihot, Anne-Laure; Jardel, Alain; Loufrani, Laurent; Henrion, Daniel

    2010-01-01

    Metabolic syndrome is associated with reduced endothelial vasodilator function. It is also associated with the induction of cyclooxygenase-2 (COX2), which produces vasoactive prostanoids. The frequency of metabolic syndrome increases with age and aging per se is a risk factor associated with reduced endothelium-mediated relaxation. Nevertheless, the combined effect of aging and metabolic syndrome on the endothelium is less known. We hypothesized that COX2 derived prostanoids may affect endothelium function in metabolic syndrome associated with aging. We used obese Zucker rats, a model of metabolic syndrome. First order mesenteric arteries were isolated from 4- and 12-month-old rats and acetylcholine (endothelium)-dependent relaxation determined using wire-myography. Endothelium-mediated relaxation, impaired in young Zucker rats (89 versus 77% maximal relaxation; lean versus Zucker), was further reduced in old Zucker rats (72 versus 51%, lean versus Zucker). The effect of the nitric oxide-synthesis inhibitor L-NAME on the relaxation was reduced in both young and old Zucker rats without change in eNOS expression level. COX inhibition (indomethacin) improved acetylcholine-mediated relaxation in old obese rats only, suggesting involvement of vasoconstrictor prostanoids. In addition, COX2 inhibition (NS398) and TxA2/PGH2 receptor blockade (SQ29548) both improved relaxation in old Zucker rat arteries. Old Zucker rats had the highest TxB2 (TxA2 metabolite) blood level associated with increased COX2 immunostaining. Chronic COX2 blockade (Celecoxib, 3 weeks) restored endothelium-dependent relaxation in old Zucker rats to the level observed in old lean rats. Thus the combination of aging and metabolic syndrome further impairs endothelium-dependent relaxation by inducing an excessive production of COX2-derived vasoconstrictor(s); possibly TxA2. PMID:21423385

  15. Cyclooxygenase-2 inhibition restored endothelium-mediated relaxation in old obese zucker rat mesenteric arteries.

    PubMed

    Vessières, Emilie; Belin de Chantemèle, Eric J; Toutain, Bertrand; Guihot, Anne-Laure; Jardel, Alain; Loufrani, Laurent; Henrion, Daniel

    2010-01-01

    Metabolic syndrome is associated with reduced endothelial vasodilator function. It is also associated with the induction of cyclooxygenase-2 (COX2), which produces vasoactive prostanoids. The frequency of metabolic syndrome increases with age and aging per se is a risk factor associated with reduced endothelium-mediated relaxation. Nevertheless, the combined effect of aging and metabolic syndrome on the endothelium is less known. We hypothesized that COX2 derived prostanoids may affect endothelium function in metabolic syndrome associated with aging. We used obese Zucker rats, a model of metabolic syndrome. First order mesenteric arteries were isolated from 4- and 12-month-old rats and acetylcholine (endothelium)-dependent relaxation determined using wire-myography. Endothelium-mediated relaxation, impaired in young Zucker rats (89 versus 77% maximal relaxation; lean versus Zucker), was further reduced in old Zucker rats (72 versus 51%, lean versus Zucker). The effect of the nitric oxide-synthesis inhibitor L-NAME on the relaxation was reduced in both young and old Zucker rats without change in eNOS expression level. COX inhibition (indomethacin) improved acetylcholine-mediated relaxation in old obese rats only, suggesting involvement of vasoconstrictor prostanoids. In addition, COX2 inhibition (NS398) and TxA2/PGH2 receptor blockade (SQ29548) both improved relaxation in old Zucker rat arteries. Old Zucker rats had the highest TxB2 (TxA2 metabolite) blood level associated with increased COX2 immunostaining. Chronic COX2 blockade (Celecoxib, 3 weeks) restored endothelium-dependent relaxation in old Zucker rats to the level observed in old lean rats. Thus the combination of aging and metabolic syndrome further impairs endothelium-dependent relaxation by inducing an excessive production of COX2-derived vasoconstrictor(s); possibly TxA2.

  16. Phenobarbital in the genetically obese Zucker rat. II. In vivo and in vitro assessments of microsomal enzyme induction.

    PubMed

    Brouwer, K L; Kostenbauder, H B; McNamara, P J; Blouin, R A

    1984-12-01

    In vivo and in vitro alterations in drug metabolism and the extent of enzyme induction of the hepatic microsomal cytochrome P-450 system were evaluated in obese and lean Zucker and lean Sprague-Dawley rats. Phenobarbital enzyme-inducing regimens were administered p.o. to achieve similar steady-state phenobarbital plasma concentrations. Control rats received p.o. placebo solution. No significant intra- or inter-strain differences in antipyrine clearance (milliliters per hour) or apparent volume of distribution (liters) were observed between the placebo-treated lean Sprague-Dawley, lean Zucker and obese Zucker rats. Intra- and inter-strain differences in hepatic microsomal protein and cytochrome P-450 content were observed. Compared to placebo, antipyrine clearance (milliliters per hour) after chronic phenobarbital pretreatment was increased in the Sprague-Dawley (198%) and lean Zucker rats (131%), but not significantly altered in the obese Zucker rats. Similarly, increases in hepatic weight, whole liver microsomal protein and cytochrome P-450 content were also observed in the Sprague-Dawley (34, 124 and 352%, respectively) and the lean Zucker rats (24, 96 and 249%, respectively). However, no significant alterations in these parameters were observed in the obese Zucker rats after phenobarbital treatment. Results from these in vivo and in vitro studies implicate alterations in drug metabolism and genetic differences in cytochrome P-450 content in Zucker rats relative to the Sprague-Dawley strain. Obese Zucker rats failed to exhibit a significant induction response after phenobarbital pretreatment.

  17. Fluoxetine alters mu opioid receptor expression in obese Zucker rat extrahypothalamic regions.

    PubMed

    Churruca, Itziar; Portillo, María P; Zumalabe, José María; Macarulla, María T; Sáenz Del Burgo, Laura; Zarate, Jon; Echevarría, Enrique

    2006-03-01

    The aim of this article was to describe the effects of chronic fluoxetine on mu opioid receptor expression in obese Zucker rat extrahypothalamic regions. Male obese Zucker (fa/fa) rats were administered with fluoxetine (10 mg/kg; i.p.) daily for two weeks. Brain regional immunostaining for mu opioid receptor was carried out. An increase in the numbers of neural cells immunostained for mu opioid receptor in caudatus-putamen, dentate gyrus, lateral septum, amygdala, and frontal, parietal, and piriform cortices was observed. Increased mu opioid receptor expression in the central amygdaloid nuclei suggests a decreased opioidergic tone at this level that could be involved in fluoxetine anorectic action.

  18. Hepatic oxidative stress, genotoxicity and vascular dysfunction in lean or obese Zucker rats.

    PubMed

    Løhr, Mille; Folkmann, Janne K; Sheykhzade, Majid; Jensen, Lars J; Kermanizadeh, Ali; Loft, Steffen; Møller, Peter

    2015-01-01

    Metabolic syndrome is associated with increased risk of cardiovascular disease, which could be related to oxidative stress. Here, we investigated the associations between hepatic oxidative stress and vascular function in pressurized mesenteric arteries from lean and obese Zucker rats at 14, 24 and 37 weeks of age. Obese Zucker rats had more hepatic fat accumulation than their lean counterparts. Nevertheless, the obese rats had unaltered age-related level of hepatic oxidatively damaged DNA in terms of formamidopyrimidine DNA glycosylase (FPG) or human oxoguanine DNA glycosylase (hOGG1) sensitive sites as measured by the comet assay. There were decreasing levels of oxidatively damaged DNA with age in the liver of lean rats, which occurred concurrently with increased expression of Ogg1. The 37 week old lean rats also had higher expression level of Hmox1 and elevated levels of DNA strand breaks in the liver. Still, both strain of rats had increased protein level of HMOX-1 in the liver at 37 weeks. The external and lumen diameters of mesenteric arteries increased with age in obese Zucker rats with no change in media cross-sectional area, indicating outward re-modelling without hypertrophy of the vascular wall. There was increased maximal response to acetylcholine-mediated endothelium-dependent vasodilatation in both strains of rats. Collectively, the results indicate that obese Zucker rats only displayed a modest mesenteric vascular dysfunction, with no increase in hepatic oxidative stress-generated DNA damage despite substantial hepatic steatosis.

  19. The metabolic clearance rate of corticosterone in lean and obese male Zucker rats

    SciTech Connect

    White, B.D.; Corll, C.B.; Porter, J.R.

    1989-06-01

    The obese Zucker rat is an animal model of human juvenile-onset obesity. These rats exhibit numerous endocrine and metabolic abnormalities. Adrenalectomy of obese rats has been shown to reduce or reverse several of these abnormalities, thereby implying that corticosterone may contribute to the expression of obesity in this animal. Furthermore, it has been shown that the circadian rhythm of plasma corticosterone is disturbed in obese Zucker rats resulting in elevated morning plasma corticosterone concentrations in obese rats as compared to lean rats. In a effort to better elucidate the mechanism of the elevated morning levels of plasma corticosterone, the metabolic clearance rate of corticosterone was determined in the morning for lean and obese male Zucker rats (12 to 20 weeks). Additionally, the biliary and urinary excretion of labeled corticosterone and/or its metabolites were determined. The metabolic clearance rate of corticosterone was significantly greater in obese rats than in their lean counterparts. Both the metabolic clearance rate and the volume of compartments significantly correlated with body weight. No correlation was found between body weight and the elimination rate constant. The increased metabolic clearance rate of obese rats appeared to be due to an increase in the physiologic distribution of corticosterone and not to an alteration in the enzymes responsible for corticosterone metabolism. It appears that the metabolic clearance rate of corticosterone in obese Zucker rats does not contribute to elevated morning concentrations of plasma corticosterone previously observed in these animals. It suggests that the adrenal corticosterone secretion rate must actually be greater than one would expect from the plasma corticosterone concentrations alone.

  20. Impulsive-choice patterns for food in genetically lean and obese Zucker rats.

    PubMed

    Boomhower, Steven R; Rasmussen, Erin B; Doherty, Tiffany S

    2013-03-15

    Behavioral-economic studies have shown that differences between lean and obese Zuckers in food consumption depend on the response requirement for food. Since a response requirement inherently increases the delay to reinforcement, differences in sensitivity to delay may also be a relevant mechanism of food consumption in the obese Zucker rat. Furthermore, the endocannabinoid neurotransmitter system has been implicated in impulsivity, but studies that attempt to characterize the effects of cannabinoid drugs (e.g., rimonabant) on impulsive choice may be limited by floor effects. The present study aimed to characterize impulsive-choice patterns for sucrose using an adjusting-delay procedure in genetically lean and obese Zuckers. Ten lean and ten obese Zucker rats chose between one lever that resulted in one pellet after a standard delay (either 1 s or 5 s) and a second lever that resulted in two or three pellets after an adjusting delay. After behavior stabilized under baseline, rimonabant (0-10 mg/kg) was administered prior to some choice sessions in the two-pellet condition. Under baseline, obese Zuckers made more impulsive choices than leans in three of the four standard-delay/pellet conditions. Additionally, in the 2-pellet condition, rimonabant increased impulsive choice in lean rats in the 1-s standard-delay condition; however, rimonabant decreased impulsive choice in obese rats in the 1-s and 5-s standard-delay conditions. These data suggest that genetic factors that influence impulsive choice are stronger in some choice conditions than others, and that the endocannabinoid system may be a relevant neuromechanism.

  1. Investigation of oxidant stress and vasodepression to glyceryl trinitrate in the obese Zucker rat in vivo

    PubMed Central

    Laight, David W; Kengatharan, K M; Gopaul, Nitin K; Änggård, Erik E; Carrier, Martin J

    1998-01-01

    We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic, chain-breaking antioxidants vitamin E (0.5% w w−1) or probucol (0.5% w w−1) or the superoxide anion scavenger tiron (1% w v−1 in drinking water).The basal plasma level of the isoprostane 8-epi-PGF2α, an in vivo marker of lipid peroxidation, was elevated by approximately 5 fold in the obese Zucker rat and markedly reduced by dietary lipophilic antioxidants and depressed by dietary tiron.Vasodepression to bolus does GTN (0.1–100 μg kg−1 i.v.), but not endothelium-dependent vasodepression to bolus dose acetylcholine (ACh, 0.02–2.0 μg kg−1 i.v.), was impaired in obese animals and completely restored by dietary antioxidants.Nitrate tolerance developed in vivo during a 1 h infusion of GTN (40 μg kg−1 min−1 i.v.) appeared more severe in obese animals. However, rapid nitrate tolerance was not affected by dietary antioxidants in either the obese or lean Zucker rat.We therefore provide evidence that elevated oxidant stress in the obese Zucker rat is associated with an impairment in nitrate vasodepressor activity. However, our data are not consistent with either a role for oxidant stress in rapid nitrate tolerance development in the anaesthetized Zucker rat or the aggravation of this tolerance by pre-existing oxidant stress. PMID:9831930

  2. Obese and lean Zucker rats demonstrate differential sensitivity to rates of food reinforcement in a choice procedure.

    PubMed

    Buckley, Jessica L; Rasmussen, Erin B

    2012-12-25

    The obese Zucker rat carries two recessive fa alleles that result in the expression of an obese phenotype. Obese Zuckers have higher food intake than lean controls in free-feed studies in which rats have ready access to a large amount of one type of food. The present study examined differences in obese and lean Zucker rats using concurrent schedules of reinforcement, which more ecologically models food selection using two food choices that have limited, but generally predictable availability. Lever-pressing of ten lean (Fa/Fa or Fa/fa) and ten obese (fa/fa) Zucker rats was placed under three concurrent variable interval variable interval (conc VI VI) schedules of sucrose and carrot reinforcement, in which the programmed reinforcer ratios for 45-mg food pellets were 5:1, 1:1, and 1:5. Allocation of responses to the two food alternatives was characterized using the generalized matching equation, which allows sensitivity to reinforcer rates (a) and bias toward one alternative (log k) to be quantified. All rats showed a bias toward sucrose, though there were no differences between lean and obese Zucker rats. In addition, obese Zucker rats exhibited higher sensitivity to reinforcement rates than lean rats. This efficient pattern of responding was related to overall higher deliveries of food pellets. Effective matching for food, then, may be another behavioral pattern that contributes to an obese phenotype.

  3. The Effect of Exercise Training on Skeletal Muscle Glucose Transorter Isoform GLUT4 Concentration in the Obese Zucker Rat

    DTIC Science & Technology

    1991-05-01

    NUMBERS The Effect of Exercise Training on Skeletal Muscle Glucose Transorter Isoform GLUT4 Concentration in the Obese Zucker Rat 6. AUTHOR(S) Eric A...Zr) THE EFFECT OF EXERCISE TRAINING ON SKELETAL MUSCLE GLUCOSE TRANSPORTER ISOFORM GLUT4 CONCENTRATION IN THE OBESE ZUCKER RAT by Eric Anthony Banks...laboratory for their help. Eric A. Banks v ABSTRACT THE EFFECT OF EXERCISE TRAINING ON SKELETAL MUSCLE GLUCOSE TRANSPORTER ISOFORM GLUT4 CONCENTRATION IN

  4. Reproductive function of the male obese Zucker rats: alteration in sperm production and sperm DNA damage.

    PubMed

    Vendramini, V; Cedenho, A P; Miraglia, S M; Spaine, D M

    2014-02-01

    Obesity has been considered a public health issue in many countries and is of increasing concern for authorities over the past 6 years. The Zucker rat is a good experimental model for obesity and diabetes studies due to its metabolic characteristics that are similar to those developed by humans. A total of 12 obese Zucker rats and their lean littermates were killed in pubertal and young adult phases for assessing organ weights (testis and epididymis), testicular histomorphometric and stereological analyses, daily sperm production, and transit time in the epididymis. Sperm integrity was also investigated in the adult animals using the Comet assay. Alterations in organ weights, seminiferous epithelium architecture, sperm production, and transit time were noticed in the pubertal fatty rats. The volume density of the lymphatic space was decreased in both the ages. Adult animals had a significant increase in the extent of damage found in sperm DNA. Our results show for the first time that leptin receptor deficiency compromises sperm production during puberty and that genetic obese Zucker rats have increased sperm DNA fragmentation.

  5. Cold-increase in brown fat thyroxine 5'-monodeiodinase is attenuated in Zucker obese rat

    SciTech Connect

    Wu, S.Y.; Stern, J.S.; Fisher, D.A.; Glick, Z.

    1987-01-01

    In this study the authors examined the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for enzymic conversion of thyroxine (T/sub 4/) to triiodothyronine (T/sub 3/) in BAT. A total of 34 lean and obese rats, approx.4 mo old were divided into three treatment groups: group 1 (5 lean and 6 obese) was fed Purina rat chow for 21 days, and group two (5 lean and 6 obese) was fed a cafeteria diet for 21 days, and groups 3 (6 lean and 6 obese) was fed Purina rat chow and maintained in the cold (8 +/- 1/sup 0/C) for 7 days. Activity of T/sub 4/ 5'-deiodinase was determined as the rate of T/sub 3/ production from added T/sub 4/ under controlled in vitro conditions. Serum T/sub 4/ and T/sub 3/ were determined by radioimmunoassay. The rate of T/sub 4/-to-T/sub 3/ conversion in BAT was similar in the lean and obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet. However, expressed per scapular BAT depot, lean rats exposed to cold displayed about a fivefold increase in BAT T/sub 3/ production whereas only a small increase was observed in the cold-exposed obese rats. Serum T/sub 3/ levels tended to be reduced in the Zucker obese rats. The data indicate a reduced capacity for T/sub 3/ production of Zucker rat BAT exposed to cold. This defect may account for the reduced tolerance of the obese animals to cold, but it does not account for their reduced diet-induced BAT thermogenesis.

  6. Pepsin Egg White Hydrolysate Ameliorates Obesity-Related Oxidative Stress, Inflammation and Steatosis in Zucker Fatty Rats

    PubMed Central

    Garcés-Rimón, M.; González, C.; Uranga, J. A.; López-Miranda, V.; López-Fandiño, R.; Miguel, M.

    2016-01-01

    The aim of this work was to evaluate the effect of the administration of egg white hydrolysates on obesity-related disorders, with a focus on lipid metabolism, inflammation and oxidative stress, in Zucker fatty rats. Obese Zucker rats received water, pepsin egg white hydrolysate (750 mg/kg/day) or Rhizopus aminopeptidase egg white hydrolysate (750 mg/kg/day) for 12 weeks. Lean Zucker rats received water. Body weight, solid and liquid intakes were weekly measured. At the end of the study, urine, faeces, different organs and blood samples were collected. The consumption of egg white hydrolysed with pepsin significantly decreased the epididymal adipose tissue, improved hepatic steatosis, and lowered plasmatic concentration of free fatty acids in the obese animals. It also decreased plasma levels of tumor necrosis factor-alpha and reduced oxidative stress. Pepsin egg white hydrolysate could be used as a tool to improve obesity-related complications. PMID:26985993

  7. Leucine and protein metabolism in obese zucker rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Glucose transport and cell surface GLUT-4 protein in skeletal muscle of the obese Zucker rat.

    PubMed

    Etgen, G J; Wilson, C M; Jensen, J; Cushman, S W; Ivy, J L

    1996-08-01

    The relationship between 3-O-methyl-D-glucose transport and 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1, 3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA)-labeled cell surface GLUT-4 protein was assessed in fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles of lean and obese (fa/fa) Zucker rats. In the absence of insulin, glucose transport as well as cell surface GLUT-4 protein was similar in both epitrochlearis and soleus muscles of lean and obese rats. In contrast, insulin-stimulated glucose transport rates were significantly higher for lean than obese rats in both soleus (0.74 +/- 0.05 vs. 0.40 +/- 0.02 mumol.g-1.10 min-1) and epitrochlearis (0.51 +/- 0.05 vs. 0.17 +/- 0.02 mumol.g-1.10 min-1) muscles. The ability of insulin to enhance glucose transport in fast- and slow-twitch muscles from both lean and obese rats corresponded directly with changes in cell surface GLUT-4 protein. Muscle contraction elicited similar increases in glucose transport in lean and obese rats, with the effect being more pronounced in fast-twitch (0.70 +/- 0.07 and 0.77 +/- 0.04 mumol.g-1.10 min-1 for obese and lean, respectively) than in slow-twitch muscle (0.36 +/- 0.03 and 0.40 +/- 0.02 mumol.g-1.10 min-1 for obese and lean, respectively). The contraction-induced changes in glucose transport directly corresponded with the observed changes in cell surface GLUT-4 protein. Thus the reduced glucose transport response to insulin in skeletal muscle of the obese Zucker rat appears to result directly from an inability to effectively enhance cell surface GLUT-4 protein.

  9. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats.

    PubMed

    Aldini, Giancarlo; Orioli, Marica; Rossoni, Giuseppe; Savi, Federica; Braidotti, Paola; Vistoli, Giulio; Yeum, Kyung-Jin; Negrisoli, Gianpaolo; Carini, Marina

    2011-06-01

    The metabolic syndrome is a risk factor that increases the risk for development of renal and vascular complications. This study addresses the effects of chronic administration of the endogenous dipeptide carnosine (β-alanyl-L-histidine, L-CAR) and of its enantiomer (β-alanyl-D-histidine, D-CAR) on hyperlipidaemia, hypertension, advanced glycation end products, advanced lipoxidation end products formation and development of nephropathy in the non-diabetic, Zucker obese rat. The Zucker rats received a daily dose of L-CAR or D-CAR (30 mg/kg in drinking water) for 24 weeks. Systolic blood pressure was recorded monthly. At the end of the treatment, plasma levels of triglycerides, total cholesterol, glucose, insulin, creatinine and urinary levels of total protein, albumin and creatinine were measured. Several indices of oxidative/carbonyl stress were also measured in plasma, urine and renal tissue. We found that both L- and D-CAR greatly reduced obese-related diseases in obese Zucker rat, by significantly restraining the development of dyslipidaemia, hypertension and renal injury, as demonstrated by both urinary parameters and electron microscopy examinations of renal tissue. Because the protective effect elicited by L- and D-CAR was almost superimposable, we conclude that the pharmacological action of L-CAR is not due to a pro-histaminic effect (D-CAR is not a precursor of histidine, since it is stable to peptidic hydrolysis), and prompted us to propose that some of the biological effects can be mediated by a direct carbonyl quenching mechanism.

  10. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats

    PubMed Central

    Aldini, Giancarlo; Orioli, Marica; Rossoni, Giuseppe; Savi, Federica; Braidotti, Paola; Vistoli, Giulio; Yeum, Kyung-Jin; Negrisoli, Gianpaolo; Carini, Marina

    2011-01-01

    Abstract The metabolic syndrome is a risk factor that increases the risk for development of renal and vascular complications. This study addresses the effects of chronic administration of the endogenous dipeptide carnosine (β-alanyl-L-histidine, L-CAR) and of its enantiomer (β-alanyl-D-histidine, D-CAR) on hyperlipidaemia, hypertension, advanced glycation end products, advanced lipoxidation end products formation and development of nephropathy in the non-diabetic, Zucker obese rat. The Zucker rats received a daily dose of L-CAR or D-CAR (30 mg/kg in drinking water) for 24 weeks. Systolic blood pressure was recorded monthly. At the end of the treatment, plasma levels of triglycerides, total cholesterol, glucose, insulin, creatinine and urinary levels of total protein, albumin and creatinine were measured. Several indices of oxidative/carbonyl stress were also measured in plasma, urine and renal tissue. We found that both L- and D-CAR greatly reduced obese-related diseases in obese Zucker rat, by significantly restraining the development of dyslipidaemia, hypertension and renal injury, as demonstrated by both urinary parameters and electron microscopy examinations of renal tissue. Because the protective effect elicited by L- and D-CAR was almost superimposable, we conclude that the pharmacological action of L-CAR is not due to a pro-histaminic effect (D-CAR is not a precursor of histidine, since it is stable to peptidic hydrolysis), and prompted us to propose that some of the biological effects can be mediated by a direct carbonyl quenching mechanism. PMID:20518851

  11. Long-term treatment of obese Zucker rats with LY255582 and other appetite suppressants.

    PubMed

    Shaw, W N

    1993-11-01

    LY255582, administered subcutaneously, decreased food intake and body weight gain of fed obese Zucker rats during the entire 30-day period of treatment. No tolerance to these biologic effects of LY255582 could be demonstrated. d-Amphetamine and naltrexone, administered subcutaneously, and d,l-fenfluramine and salbutamol, administered orally, decreased food intake for no more than 6 to 12 days, in contrast to the long-lasting effects of LY255582. Salbutamol suppressed the appetite of obese rats for 3-4 days only. After an additional 12 days of treatment, weight gain decreased significantly accompanied by no appetite suppression. Thus, there is a difference in the duration of action of the opioid antagonist, LY255582, when compared to amphetamine, fenfluramine, naltrexone, and salbutamol, on food intake and body weight gain of obese rats.

  12. 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.

  13. Corn oil, but not cocaine, is a more effective reinforcer in obese than in lean Zucker rats.

    PubMed

    Townsend, Edward A; Beloate, Lauren N; Huskinson, Sally L; Roma, Peter G; Freeman, Kevin B

    2015-05-01

    Obesity is associated with abnormal brain reactivity in response to palatable food consumption, a factor that may contribute to non-homeostatic eating. However, little is known about how obesity interacts with the reinforcing effects of highly palatable constituents of food (e.g., fat), and if altered reinforcement processes associated with obesity generalize to non-food reinforcers. The current study compared the reinforcing effects of a fat (corn oil) and a drug of abuse (cocaine) in obese and lean Zucker rats. Specifically, obese and lean Zucker rats self-administered corn oil or intravenous cocaine in a behavioral economic demand procedure. For corn oil, maximum demand was higher and demand elasticity was lower in the obese rats compared to their lean counterparts. However, there were no differences in demand for cocaine between the obese and lean rats. These results demonstrate that a fat in the form of corn oil is a more effective reinforcer in obese Zucker rats. However, the fact that demand for cocaine was not different between the obese and lean rats suggests that differences in reward mechanisms may be reinforcer-specific and do not necessarily generalize to non-food reinforcers.

  14. Effects of fluoxetine administration on hypothalamic melanocortin system in obese Zucker rats.

    PubMed

    Churruca, I; Portillo, M P; Casis, L; Gutiérrez, A; Macarulla, M T; Echevarría, E

    2008-06-01

    The aim of the present work was to study the potential involvement of melanocortin system in the anorectic mechanism of fluoxetine, a selective serotonin reuptake inhibitors, in obese Zucker rats. Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. RT-PCR for pro-opiomelanocortin (POMC), Agouti gene related peptide (AgRP) and melanocortin receptor 4 (MC4-R) in the hypothalamus, as well as regional immunostaining for alpha-melanocyte stimulating hormone (alpha-MSH) and MC4-R were carried out. Fluoxetine administration increased POMC expression and reduced MC4-R expression in the hypothalamus, without changes in AgRP mRNA levels. Moreover, an increase in the numbers of alpha-MSH positively immunostained neural cells in the hypothalamic arcuate nucleus (ARC), as well as a significant decrease in the numbers of neural cells positively immunostained for MC4-R in the paraventricular nucleus (PVN), without changes in lateral hypothalamic area (LHA), were observed. These results suggest the involvement of alpha-MSH in central fluoxetine anorectic action.

  15. Effects of fluoxetine administration on regional galanin expression in obese Zucker rat hypothalamus.

    PubMed

    Churruca, Itziar; Portillo, María P; Gutiérreza, Arantza; Casis, Luis; Macarulla, María Teresa; Zarate, Jon; Echevarría, Enrique

    2004-06-01

    The aim of the present work was to study the potential involvement of hypothalamic galanin system in the anorectic mechanism of fluoxetine in obese Zucker rats. Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. Significant decreases in food intake, final body weight and total body fat were observed after fluoxetine treatment. Although fluoxetine-treated rats showed a decrease in urine elimination, this effect was not enough to compensate decreased water intake, leading to dehydration, as showed by decreased body water content. Chronic fluoxetine administration increased the numbers of galanin positively immunostained neural cells in medial and lateral preoptic areas, lateral hypothalamic area and paraventricular nucleus (rostral and magnocellular regions), without changes in dorsomedial, ventromedial, supraoptic, suprachiasmatic and arcuate nuclei. Taken into account that galanin stimulates appetite, these results could represent rather a compensatory response against reduced food intake than a direct anorectic mechanism. Changes in the magnocellular region of the hypothalamic paraventricular nucleus suggest a role for galanin neural circuits at this level in fluoxetine-induced hydro-osmotic impairment.

  16. Diminished natriuretic response to dopamine D1 receptor agonist, SKF-38393 in obese Zucker rats.

    PubMed

    Marwaha, Aditi; Lokhandwala, Mustafa F

    2003-11-01

    Dopamine causes natriuresis and diuresis via activation of D1 receptors located on the renal proximal tubules and subsequent inhibition of the sodium transporters, Na-H exchanger and Na+/K+ ATPase. We have reported that dopamine fails to inhibit the activities of these two transporters in the obese Zucker rats (OZR). The present study was designed to examine the functional consequence of this phenomenon by determining the natriuretic and diuretic response to D1 receptor activation in lean Zucker rats (LZR) and OZR. In 11-12 week-old OZR and LZR, natriuretic and diuretic responses to intravenously administered D1 receptor agonist, SKF 38393 (3 microg/kg/min for 30 min) were measured under Inactin anesthesia. Plasma insulin and glucose levels were significantly higher in the obese rats as compared to the lean rats. Intravenous infusion of SKF 38393 caused significant increases in urine flow, urinary sodium excretion (U(Na)V), fractional excretion of sodium (FE(Na)), and glomerular filtration rate (GFR) in the lean rats. However, the natriuretic and diuretic response to SKF 38393 was markedly blunted in OZR. Infusion of SKF 38393 did not cause significant changes in the mean blood pressure and heart rate in either of the two groups. We suggest that the diminished natriuretic response to D1 receptor activation in OZR is the consequence of the previously reported defect in the D1 receptor-G-protein coupling and the failure of dopamine to inhibit the sodium transporters in these animals.

  17. Upregulation of orexin receptor in paraventricular nucleus promotes sympathetic outflow in obese Zucker rats.

    PubMed

    Zhou, Jing-Jing; Yuan, Fang; Zhang, Yi; Li, De-Pei

    2015-12-01

    Sympathetic vasomotor tone is elevated in obesity-related hypertension. Orexin importantly regulates energy metabolism and autonomic function. We hypothesized that alteration of orexin receptor in the paraventricular nucleus (PVN) of the hypothalamus leads to elevated sympathetic vasomotor tone in obesity. We used in vivo measurement of sympathetic vasomotor tone and microinjection into brain nucleus, whole-cell patch clamp recording in brain slices, and immunocytochemical staining in obese Zucker rats (OZRs) and lean Zucker rats (LZRs). Microinjection of orexin 1 receptor (OX1R) antagonist SB334867 into the PVN reduced basal arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in anesthetized OZRs but not in LZRs. Microinjection of orexin A into the PVN produced greater increases in ABP and RSNA in OZRs than in LZRs. Western blot analysis revealed that OX1R expression levels in the PVN were significantly increased in OZRs compared with LZRs. OX1R immunoreactivity was positive in retrogradely labeled PVN-spinal neurons. The basal firing rate of labeled PVN-spinal neurons was higher in OZRs than in LZRs. SB334867 decreased the basal firing activity of PVN-spinal neurons in OZRs but had no effect in LZRs. Orexin A induced a greater increase in the firing rate of PVN-spinal neurons in OZRs than in LZRs. In addition, orexin A induced larger currents in PVN-spinal neurons in OZRs than in LZRs. These data suggest that upregulation of OX1R in the PVN promotes hyperactivity of PVN presympathetic neurons and elevated sympathetic outflow in obesity.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26475592

  19. 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.

  20. Flow-induced remodeling in resistance arteries from obese Zucker rats is associated with endothelial dysfunction.

    PubMed

    Bouvet, Céline; Belin de Chantemèle, Eric; Guihot, Anne-Laure; Vessières, Emilie; Bocquet, Arnaud; Dumont, Odile; Jardel, Alain; Loufrani, Laurent; Moreau, Pierre; Henrion, Daniel

    2007-07-01

    Chronic increases in blood flow increase arterial diameter and NO-dependent dilation in resistance arteries. Because endothelial dysfunction accompanies metabolic syndrome, we hypothesized that flow-mediated remodeling might be impaired in obese rat resistance arteries. Obese and lean Zucker rat mesenteric resistance arteries were exposed to chronic flow increases through arterial ligation in vivo: arteries exposed to high flow were compared with normal flow arteries. Diameter was measured in vitro in cannulated arteries using pressure arteriography. After 7 days, outward remodeling (diameter increased from 346+/-9 to 412+/-11 mum at 100 mm Hg) occurred in lean high-flow arteries. Endothelium-dependent tone was reduced in high-flow arteries from obese rats by contrast with lean animals. On the other hand, diameter enlargement occurred similarly in the 2 strains. The involvement of NO in endothelium-dependent dilation (evidenced by NO blockade) and endothelial NO synthase phosphorylation was smaller in obese than in lean rats. Superoxide anion and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunit expression (p67phox and gp91phox) increased in obese rats and were higher in high-flow than in control arteries. Acute Tempol (a catalase mimetic), catalase plus superoxide dismutase, and l-arginine plus tetrahydrobiopterin restored endothelium-dependent dilation in obese rat normal and high-flow arteries to the level found in lean control arteries. Thus, flow-induced remodeling in obese resistance arteries was associated with a reduced endothelium-mediated dilation because of a decreased NO bioavailability and an excessive superoxide production. This dysfunction might have negative consequences in ischemic diseases in patients with obesity or metabolic syndrome.

  1. Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats.

    PubMed

    Llarena, Marta; Andrade, Fernando; Hasnaoui, Mounia; Portillo, María P; Pérez-Matute, Patricia; Arbones-Mainar, Jose M; Hijona, Elizabeth; Villanueva-Millán, María Jesús; Aguirre, Leixuri; Carpéné, Christian; Aldámiz-Echevarría, Luis

    2016-09-01

    Obesity-associated nephropathy is considered to be a leading cause of end-stage renal disease. Resveratrol supplementation represents a promising therapy to attenuate kidney injury, but the poor solubility and limited bioavailability of this polyphenol limits its use in dietary intervention. Piceatannol, a resveratrol analogue, has been suggested as a better option. In this study, we aimed to provide evidence of a preventive action of piceatannol in very early stages of obesity-associated nephropathy. Thirty obese Zucker rats were divided into three experimental groups: one control and two groups orally treated for 6 weeks with 15 and 45 mg piceatannol/kg body weight/day. Enzyme-linked immunosorbent assays (ELISA) were used to determine renal and urinary kidney injury molecule-1 (Kim-1), renal fibrosis markers (transforming growth factor β1 and fibronectin) and renal sirtuin-1 protein. Oxidative stress was assessed in the kidney by measuring lipid peroxidation and nitrosative stress (thiobarbituric acid reactive substrates and 3-nitrotyrosine levels, respectively) together with the activity of the antioxidant enzyme superoxide dismutase. Renal fatty acids profile analysis was performed by thin-layer and gas chromatography. Piceatannol-treated rats displayed lower levels of urinary and renal Kim-1. Renal fibrosis biomarkers and lipid peroxidation exhibited a tendency to decrease in the piceatannol-treated groups. Piceatannol treatment did not modify superoxide dismutase activity or sirtuin-1 protein levels, while it seemed to increase the levels of polyunsaturated and omega-6 polyunsaturated fatty acids in the kidneys. Our findings suggest a mild renoprotective effect of piceatannol in obese Zucker rats and the need of intervention at early stages of renal damage.

  2. Anti-obesity effects of onion extract in Zucker diabetic fatty rats.

    PubMed

    Yoshinari, Orie; Shiojima, Yoshiaki; Igarashi, Kiharu

    2012-10-22

    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.

  3. Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats.

    PubMed

    Marchionne, Elizabeth M; Diamond-Stanic, Maggie K; Prasonnarong, Mujalin; Henriksen, Erik J

    2012-01-01

    We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker (fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser(473) phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the

  4. 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.

  5. Exaggerated sympathoexcitatory reflexes develop with changes in the rostral ventrolateral medulla in obese Zucker rats.

    PubMed

    Huber, Domitila A; Schreihofer, Ann M

    2016-08-01

    Obesity leads to altered autonomic reflexes that reduce stability of mean arterial pressure (MAP). Sympathoinhibitory reflexes such as baroreflexes are impaired, but reflexes that raise MAP appear to be augmented. In obese Zucker rats (OZR) sciatic nerve stimulation evokes larger increases in MAP by unknown mechanisms. We sought to determine the autonomic underpinnings of this enhanced somatic pressor reflex and whether other sympathoexcitatory reflexes are augmented. We also determined whether their final common pathway, glutamatergic activation of the rostral ventrolateral medulla (RVLM), was enhanced in male OZR compared with lean Zucker rats (LZR). Sciatic nerve stimulation or activation of the nasopharyngeal reflex evoked larger rises in splanchnic sympathetic nerve activity (SNA) (79% and 45% larger in OZR, respectively; P < 0.05) and MAP in urethane-anesthetized, ventilated, paralyzed adult OZR compared with LZR. After elimination of baroreflex feedback by pharmacological prevention of changes in MAP and heart rate, these two sympathoexcitatory reflexes were still exaggerated in OZR (167% and 69% larger, respectively, P < 0.05). In adult OZR microinjections of glutamate, AMPA, or NMDA into the RVLM produced larger rises in SNA (∼61% larger in OZR, P < 0.05 for each drug) and MAP, but stimulation of axonal fibers in the upper thoracic spinal cord yielded equivalent responses in OZR and LZR. In juvenile OZR and LZR, sympathoexcitatory reflexes and physiological responses to RVLM activation were comparable. These data suggest that the ability of glutamate to activate the RVLM becomes enhanced in adult OZR and may contribute to the development of exaggerated sympathoexcitatory responses independent of impaired baroreflexes.

  6. Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors

    PubMed Central

    Blaha, Igor; Recio, Paz; Martínez, María Pilar; López-Oliva, María Elvira; Ribeiro, Ana S. F.; Agis-Torres, Ángel; Martínez, Ana Cristina; Benedito, Sara; García-Sacristán, Albino; Fernandes, Vítor S.; Hernández, Medardo

    2016-01-01

    Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR. PMID:27285468

  7. Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors.

    PubMed

    Blaha, Igor; Recio, Paz; Martínez, María Pilar; López-Oliva, María Elvira; Ribeiro, Ana S F; Agis-Torres, Ángel; Martínez, Ana Cristina; Benedito, Sara; García-Sacristán, Albino; Fernandes, Vítor S; Hernández, Medardo

    2016-01-01

    Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR.

  8. Fatty acids impair endothelium-dependent vasorelaxation: a link between obesity and arterial stiffness in very old Zucker rats.

    PubMed

    Sloboda, Natacha; Fève, Bruno; Thornton, Simon N; Nzietchueng, Rosine; Regnault, Véronique; Simon, Ginny; Labat, Carlos; Louis, Huguette; Max, Jean-Pierre; Muscat, Adeline; Osborne-Pellegrin, Mary; Lacolley, Patrick; Benetos, Athanase

    2012-09-01

    To analyze age-related interactions between obesity, its associated metabolic disorders, and macrocirculation, we studied large artery stiffness and fatty acid responsiveness in lean and obese Zucker rats, aged 25 (adult) and 80 weeks (very old). Systolic arterial pressure was higher in old obese than in old lean rats (178 ± 10 vs 134 ± 8 mmHg, respectively). Carotid elastic modulus-wall stress curves showed increased age-dependent arterial stiffening, which was greater in obese animals. Old obese exhibited endothelial dysfunction with increased systemic oxidative stress. Adult obese had elevated plasma free fatty acid levels (1,866 ± 177 vs 310 ± 34 μg/μL in lean animals). In old obese, linoleate and palmitate increased contractility to phenylephrine and reduced relaxation to acetylcholine. Thus, obesity at 25 weeks appears to trigger accelerated arterial aging observed at 80 weeks. The early increase in free fatty acids may be a key effector in the severe arterial stiffness of the aged obese Zucker model.

  9. Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle

    PubMed Central

    2013-01-01

    Background In the present study, we tested the hypothesis that carnitine supplementation counteracts obesity-induced muscle fiber transition from type I to type II. Methods 24 obese Zucker rats were randomly divided into two groups of 12 rats each (obese control, obese carnitine) and 12 lean Zucker rats were selected for lean control group. A control diet was given to both control groups and a carnitine supplemented diet (3 g/kg diet) was given to obese carnitine group for 4 wk. Components of the muscle fiber transformation in skeletal muscle were examined. Results The plasma level of carnitine were lower in the obese control group compared to the lean control group and higher in the obese carnitine group than in the other groups (P < 0.05). Plasma concentrations of triglycerides and non-esterified fatty acids were increased in obese animals compared to lean animals and the obese carnitine group had lower level compared to the obese control group (P < 0.05). The obese carnitine group had an increased number of type I muscle fibers and higher mRNA levels of type I fiber-specific myosin heavy chain, regulators of muscle fiber transition and of genes involved in carnitine uptake, fatty acid transport, β-oxidation, angiogenesis, tricarboxylic acid cycle and thermo genesis in M. rectus femoris compared to the other groups (P < 0.05). Conclusion The results demonstrate that carnitine supplementation to obese Zucker a rat counteracts the obesity-induced muscle fiber transition and restores the muscle oxidative metabolic phenotype. Carnitine supplementation is supposed to be beneficial for the treatment of elevated levels of plasma lipids during obesity or diabetes. PMID:23842456

  10. Beneficial effects of melatonin on obesity and lipid profile in young Zucker diabetic fatty rats.

    PubMed

    Agil, Ahmad; Navarro-Alarcón, Miguel; Ruiz, Rosario; Abuhamadah, Sawsan; El-Mir, Mohamad-Yehia; Vázquez, Gumersindo Fernández

    2011-03-01

    The study objective was to investigate the effects of melatonin on obesity and obesity-associated systolic hypertension and dyslipidemia in young male Zucker diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome. ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups (n=10): naive (N), vehicle-treated (V), and melatonin-treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. Melatonin reduced mean weight gain (51±2/100g BW) versus N-ZDF group (58±3, P<0.05) without food intake differences. M-ZDF rats showed an apparent reduction in systolic hypertension that proved not to be statistically significant, and a significant improvement in dyslipidemia, with a reduction in hypertriglyceridemia from 580±40 to 420.6±40.9mg/dL (P<0.01). Melatonin raised high-density-lipoprotein (HDL) cholesterol in ZDF (from 81.6±4.9 to 103.1±4.5mg/dL, P<0.01) and ZL rats (from 62.8±4.8 to 73.5±4.8mg/dL, P<0.05) and significantly reduced low-density-lipoprotein (LDL) cholesterol in ZDF rats from 5.20±0.4 to 4.14±0.3 mg/dL (P<0.05) but had no effect on total cholesterol levels. To our knowledge, this is the first evidence of a positive effect of melatonin on overweight and lipid pattern of obese Zucker diabetic rats, supporting the proposition that melatonin administration may ameliorate overweight and lipid metabolism in humans. Because these benefits occurred in youth, before advanced metabolic and vascular complications, melatonin might help to prevent cardiovascular disease associated with obesity and dyslipidemia.

  11. 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

  12. Activity of thyroxine 5' deiodinase in brown fat of lean and obese zucker rats

    SciTech Connect

    Wu, S.Y.; Fisher, D.A.; Stern, J.S.; Glick, Z.

    1986-03-01

    This study examines the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for conversion of T/sub 4/ to T/sub 3/ in BAT, through activity of T/sub 4/ 5' deiodinase. Eighteen lean (Fa/.) and 18 age matched obese (fa/fa), about 16 weeks old, were each divided into 3 groups (n=6 per group). Group 1 and 2 were fed Purina Rat Chow and a cafeteria diet respectively for 21 days, and maintained at 22/sup 0/C+/-2. Group 3 was fed rat chow and maintained at 8/sup 0/C+/-1 for 7 days. Activity of T/sub 4/5'deiodinase was determined in vitro. T/sub 3/ was measured by a radioimmunoassay. The rate of T/sub 4/ to T/sub 3/ conversion was similar in the lean and the obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet (about 40 to 50 pmol T/sub 3//scapular BAT depot, per hour). However, lean rats exposed to the cold displayed about a 5 fold increase in T/sub 4/5' deiodinase activity (p<0.0001), with only a small increase displayed by the cold exposed obese rats. Our data suggest that a reduced capacity of the brown rat to produce T/sub 3/ may account for the reduced tolerance of obese animals to cold, but it does not account for their reduced diet induced BAT thermogenesis.

  13. Reduced Endothelium-Dependent Relaxation to Anandamide in Mesenteric Arteries from Young Obese Zucker Rats

    PubMed Central

    Lobato, Nubia S.; Filgueira, Fernando P.; Prakash, Roshini; Giachini, Fernanda R.; Ergul, Adviye; Carvalho, Maria Helena C.; Webb, R. Clinton; Tostes, Rita C.; Fortes, Zuleica B.

    2013-01-01

    Impaired vascular function, manifested by an altered ability of the endothelium to release endothelium-derived relaxing factors and endothelium-derived contracting factors, is consistently reported in obesity. Considering that the endothelium plays a major role in the relaxant response to the cannabinoid agonist anandamide, the present study tested the hypothesis that vascular relaxation to anandamide is decreased in obese rats. Mechanisms contributing to decreased anandamide-induced vasodilation were determined. Resistance mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs) were used. Vascular reactivity was evaluated in a myograph for isometric tension recording. Protein expression and localization were analyzed by Western blotting and immunofluorescence, respectively. Vasorelaxation to anandamide, acetylcholine, and sodium nitroprusside, as well as to CB1, CB2, and TRPV1 agonists was decreased in endothelium-intact mesenteric arteries from OZRs. Incubation with an AMP-dependent protein kinase (AMPK) activator or a fatty acid amide hydrolase inhibitor restored anandamide-induced vascular relaxation in OZRs. CB1 and CB2 receptors protein expression was decreased in arteries from OZRs. Incubation of mesenteric arteries with anandamide evoked endothelial nitric oxide synthase (eNOS), AMPK and acetyl CoA carboxylase phosphorylation in LZRs, whereas it decreased phosphorylation of these proteins in OZRs. In conclusion, obesity decreases anandamide-induced relaxation in resistance arteries. Decreased cannabinoid receptors expression, increased anandamide degradation, decreased AMPK/eNOS activity as well as impairment of the response mediated by TRPV1 activation seem to contribute to reduce responses to cannabinoid agonists in obesity. PMID:23667622

  14. Satellite cell proliferation is reduced in muscles of obese Zucker rats but restored with loading.

    PubMed

    Peterson, Jonathan M; Bryner, Randall W; Alway, Stephen E

    2008-08-01

    The obese Zucker rat (OZR) is a model of metabolic syndrome, which has lower skeletal muscle size than the lean Zucker rat (LZR). Because satellite cells are essential for postnatal muscle growth, this study was designed to determine whether reduced satellite cell proliferation contributes to reduced skeletal mass in OZR vs. LZR. Satellite cell proliferation was determined by a constant-release 5-bromo-2-deoxyuridine (BrdU) pellet that was placed subcutaneously in each animal. Satellite cell proliferation, as determined by BrdU incorporation, was significantly attenuated in control soleus and plantaris muscles of the OZR compared with that shown in the LZR. To determine whether this attenuation of satellite cell activity could be rescued in OZR muscles, soleus and gastrocnemius muscles were denervated, placing a compensatory load on the plantaris muscle. In the LZR and the OZR after 21 days of loading, increases of approximately 25% and approximately 30%, respectively, were shown in plantaris muscle wet weight compared with that shown in the contralateral control muscle. The number of BrdU-positive nuclei increased similarly in loaded plantaris muscles from LZR and OZR. Myogenin, MyoD, and Akt protein expressions were lower in control muscles of OZR than in those of the LZR, but they were all elevated to similar levels in the loaded plantaris muscles of OZR and LZR. These data indicate that metabolic syndrome may reduce satellite cell proliferation, and this may be a factor that contributes to the reduced mass in control muscles of OZR; however, satellite cell proliferation can be restored with compensatory loading in OZR.

  15. An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat.

    PubMed

    Bernard, Jeffrey R; Liao, Yi-Hung; Ding, Zhenping; Hara, Daisuke; Kleinert, Maximilian; Nelson, Jeffrey L; Ivy, John L

    2013-07-01

    The purpose of this investigation was to test an amino acid mixture on glucose tolerance in obese Zucker rats [experiment (Exp)-1] and determine whether differences in blood glucose were associated with alterations in muscle glucose uptake [experiment (Exp)-2]. Exp-1 rats were gavaged with either carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1), carbohydrate plus amino acid mixture with increased leucine concentration (OB-AA-2) or water (OB-PLA). The glucose response in OB-AA-1 and OB-AA-2 were similar, and both were lower compared to OB-CHO. This effect of the amino acid mixtures did not appear to be solely attributable to an increase in plasma insulin. Rats in Exp-2 were gavaged with carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1) or water (OB-PLA). Lean Zuckers were gavaged with carbohydrate (LN-CHO). Fifteen minutes after gavage, a radiolabeled glucose analog was infused through a catheter previously implanted in the right jugular vein. Blood glucose was significantly lower in OB-AA-1 compared to OB-CHO while the insulin responses were similar. Glucose uptake was greater in OB-AA-1 compared with OB-CHO, and similar to that in LN-CHO in red gastrocnemius muscle (5.15 ± 0.29, 3.8 ± 0.27, 5.18 ± 0.34 µmol/100 g/min, respectively). Western blot analysis showed that Akt substrate of 160 kDa (AS160) phosphorylation was enhanced for OB-AA-1 and LN-CHO compared to OB-CHO. These findings suggest that an amino acid mixture improves glucose tolerance in an insulin resistant model and that these improvements are associated with an increase in skeletal muscle glucose uptake possibly due to improved intracellular signaling.

  16. Molecules implicated in glucose homeostasis are differentially expressed in the trachea of lean and obese Zucker rats.

    PubMed

    Merigo, F; Boschi, F; Lasconi, C; Benati, D; Sbarbati, A

    2016-02-01

    Recent studies indicate that the processes mediated by the (T1R2/T1R3) glucose/sugar receptor of gustatory cells in the tongue, and hormones like leptin and ghrelin contribute to the regulation of glucose homeostasis. Altered plasma levels of leptin and ghrelin are associated with obesity both in humans and rodents. In the present study, we evaluated the ultrastructure of the mucosa, and the expression of molecules implicated in the regulation of glucose homeostasis (GLUT2, SGLT1, T1R3, ghrelin and its receptor) in the trachea of an animal model of obesity (Zucker rats). We found that the tracheal epithelium of obese animals was characterized by the presence of poorly differentiated cells. Ciliated and secretory cells were the cell lineages with greatest loss of differentiation. Severe epithelial alterations were associated with marked deposit of extracellular matrix in the lamina propria. The expression pattern of GLUT2 and SGLT1 glucose transporters was similar in the trachea of both the Zucker rat genotypes, whereas that of T1R3 was reduced in ciliated cells of obese rats. A different immunolocalization for ghrelin was also found in the trachea of obese rats. In conclusion, the tracheal morphological alterations in obese animals seem to compromise the expression of molecules involved in the homeostasis of glucose.

  17. Crinophagy in Thyroid Follicular and Parafollicular Cells of Male Obese Zucker Rat.

    PubMed

    Gilloteaux, Jacques; Pardhan, Danish

    2015-01-01

    Comparison between lean (Fa/?) and obese (fa/fa) young adult male Zucker rat thyroids reveals that obese rats display larger clusters of parafollicular cells than the lean ones with a lesser blood supply. Fa/? thyroid typically shows single or "twin" C cells in follicles; fa/fa parafollicular cells appear with three functional aspects. Crinophagy is found in the fa/fa C cells amassing numerous aberrant calcitonin-containing vesicles among which lysosomes build these autophagic bodies by capturing vesicle contents, other organelles and, fusing with each other, increase their size. Other C cells contain many secretory vesicles but show few or no crinophagic structures. Another parafollicular cell type is revealed with scant organelles and highly contrasted secretory vesicles, different from calcitonin. Hypercalcemia of fa/fa rats corresponds to increased C cells population with accrued calcitonin production but a low calcitonin plasma level - verified by others - is likely caused by crinophagy of the altered vesicles. In addition, the T thyrocytes of fa/fa rats exhibit crinophagy bodies; this can confirm their hypothyroidism. Possibly, the known leptin mutation along with other unknown paracrine secretions alter both T and C thyrocytes' functions of the fa/fa rats, allowing high intracellular calcium and lower pH favoring autophagocytosis. Other longitudinal, interdisciplinary studies should further clarify the complex paracrine interactions existing between these endocrine structures because this animal model could be useful to understand human defects, such as the metabolic syndrome that involves obesity, cardiovascular, renal, hepatic, non-insulin dependent diabetes mellitus (NIDDM), hypothyroidism defects, as well as the etiology of thyroid medullary tumors.

  18. Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats.

    PubMed

    Legette, Leecole L; Luna, Arlyn Y Moreno; Reed, Ralph L; Miranda, Cristobal L; Bobe, Gerd; Proteau, Rosita R; Stevens, Jan F

    2013-07-01

    Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid-chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (p<0.05) elevated in the highest dose group. There was a dose-dependent effect on body weight and plasma glucose levels. The highest dose group (n=6) had significantly lower plasma glucose levels compared to the control group (n=6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group (16.9 mg/kg BW) compared to rats that received no xanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome.

  19. Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metabolism and Host-Microbial Interactions.

    PubMed

    Phetcharaburanin, Jutarop; Lees, Hannah; Marchesi, Julian R; Nicholson, Jeremy K; Holmes, Elaine; Seyfried, Florian; Li, Jia V

    2016-06-03

    The Zucker (fa/fa) rat is a valuable and extensively utilized model for obesity research. However, the metabolic networks underlying the systemic response in the obese Zucker rats remain to be elucidated. This information is important to further our understanding of the circulation of the microbial or host-microbial metabolites and their impact on host metabolism. (1)H nuclear magnetic resonance spectroscopy-based metabolic profiling was used to probe global metabolic differences in portal vein and peripheral blood plasma, urine and fecal water between obese (fa/fa, n = 12) and lean (fa/+, n = 12) Zucker rats. Urinary concentrations of host-microbial co-metabolites were found to be significantly higher in lean Zucker rats. Higher concentrations of fecal lactate, short chain fatty acids (SCFAs), 3-hydroxyphenyl propionic acid and glycerol, and lower levels of valine and glycine were observed in obese rats compared with lean animals. Regardless of phenotype, concentrations of SCFAs, tricarboxylic acid cycle intermediates, and choline metabolites were higher in portal vein blood compared to peripheral blood. However, higher levels of succinate, phenylalanine and tyrosine were observed in portal vein blood compared with peripheral blood from lean rats but not in obese rats. Our findings indicate that the absorption of propionate, acetate, choline, and trimethylamine is independent of the Zucker rat phenotypes. However, urinary host-microbial co-metabolites were highly associated with phenotypes, suggesting distinct gut microbial metabolic activities in lean and obese Zucker rats. This work advances our understanding of metabolic processes associated with obesity, particularly the metabolic functionality of the gut microbiota in the context of obesity.

  20. Differential adipogenic and inflammatory properties of small adipocytes in Zucker Obese and Lean rats.

    PubMed

    Liu, Alice; Sonmez, Alper; Yee, Gail; Bazuine, Merlijn; Arroyo, Matilde; Sherman, Arthur; McLaughlin, Tracey; Reaven, Gerald; Cushman, Samuel; Tsao, Philip

    2010-10-01

    We recently reported that a preponderance of small adipose cells, decreased expression of cell differentiation markers, and enhanced inflammatory activity in human subcutaneous whole adipose tissue were associated with insulin resistance. To test the hypothesis that small adipocytes exhibited these differential properties, we characterised small adipocytes from epididymal adipose tissue of Zucker Obese (ZO) and Lean (ZL) rats. Rat epididymal fat pads were removed and adipocytes isolated by collagenase digestion. Small adipocytes were separated by sequential filtration through nylon meshes. Adipocytes were fixed in osmium tetroxide for cell size distribution analysis via Beckman Coulter Multisizer. Quantitative real-time PCR for cell differentiation and inflammatory genes was performed. Small adipocytes represented a markedly greater percentage of the total adipocyte population in ZO than ZL rats (58±4% vs. 12±3%, p<0.001). In ZO rats, small as compared with total adipocytes had 4-fold decreased adiponectin, and 4-fold increased visfatin and IL-6 levels. Comparison of small adipocytes in ZO versus ZL rats revealed 3-fold decreased adiponectin and PPARγ levels, and 2.5-fold increased IL-6. In conclusion, ZO rat adipose tissue harbours a large proportion of small adipocytes that manifest impaired cell differentiation and pro-inflammatory activity, two mechanisms by which small adipocytes may contribute to insulin resistance.

  1. 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.

  2. AT2 receptor non-peptide agonist C21 promotes natriuresis in obese Zucker rats.

    PubMed

    Ali, Quaisar; Hussain, Tahir

    2012-06-01

    Previously, we demonstrated that angiotensin II type 2 (AT(2)) receptors have a role in natriuresis in obese Zucker rats (OZR). In the present study, we investigated the role of a novel, non-peptide agonist, C21, in natriuresis via AT(2) receptor activation in OZR. Infusion of C21 (1 and 5 μg kg(-1) min(-1)) into rats under anesthesia caused a dose-dependent increase in urine flow (UF) and urinary Na volume (U(Na)V). These effects of C21 were blocked by pre-infusion of the AT(2) receptor antagonist, PD123319, (50 μg kg(-1) min(-1)), suggesting involvement of the AT(2) receptor. Infusion of C21 (5 μg kg(-1) min(-1)) significantly increased the fractional excretion of sodium without changing the glomerular filtration rate or blood pressure, suggesting a tubular effect. Similarly, C21 infusion increased the fractional excretion of lithium, suggesting a proximal tubular effect. Furthermore, we tested the effect of C21 on natriuresis after blocking two main, distal-nephron Na transporters, the epithelial Na channels (ENaC), with amiloride (AM, 3 mg kg(-1) body wt), and the NaCl cotransporters (NCC), with bendroflumethiazide (BFTZ, 7 mg kg(-1) body wt). Infusion of AM + BFTZ caused significant increases in both diuresis and natriuresis, which were further increased by infusion of C21 (5 μg kg(-1) min(-1)). Natriuresis in response to C21 was associated with increases in urinary NO and cGMP levels. The data indicate that the AT(2) receptor agonist, C21, promotes natriuresis via AT(2) receptor activation and that this effect is potentially based in the proximal tubules and linked to the nitric oxide/cyclic guanosine monophosphate pathway. The natriuretic response to C21 may have therapeutic significance by improving kidney function in obesity.

  3. 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.

  4. Cyclooxygenase-2-derived prostanoids reduce inward arterial remodeling induced by blood flow reduction in old obese Zucker rat mesenteric arteries.

    PubMed

    Vessières, Emilie; Belin de Chantemèle, Eric J; Guihot, Anne-Laure; Jardel, Alain; Toutain, Bertrand; Loufrani, Laurent; Henrion, Daniel

    2013-01-01

    Obesity is associated with altered arterial structure and function leading to arterial narrowing in most vascular beds, especially when associated with aging. Nevertheless, mesenteric blood flow remains elevated in obese rats, although the effect of aging remains unknown. We investigated mesenteric artery narrowing following blood flow reduction in vivo in 3- and 12-month-old obese Zucker rats. After 21 days, inward remodeling occurred in low flow (LF) arteries in young and old lean rats and in young obese rats (30% diameter reduction). Diameter did not significantly decrease in old obese rats. Phenylephrine-mediated contraction was reduced by approximately 20% in LF arteries in all groups but in old obese rat arteries in which the decrease reached 80%. LF arteries expressed cyclooxygenase-2 and blood 6-keto-PGF1alpha (prostacyclin metabolite) was elevated in old obese rats. In old obese rats, acute cyclooxygenase-2 blockade restored phenylephrine-mediated contraction in LF arteries and chronic cyclooxygenase-2 blockade restored inward remodeling and contractility to control level. Thus, in old obese rats, cyclooxygenase-2-derived prostacyclin prevented the diameter reduction induced by a chronic decrease in blood flow. This adaptation is in favor of a preserved perfusion of the mesentery by contrast with other vascular territories, possibly amplifying the vascular disorders occurring in obesity.

  5. Chronic AT2 receptor activation attenuates renal AT1 receptor function and blood pressure in obese Zucker rats

    PubMed Central

    Ali, Quaisar; Wu, Yonnie; Hussain, Tahir

    2013-01-01

    Abnormal regulation of the renin angiotensin system such as enhanced renal AT1R function and reduced ACE2 activity contributes to obesity-related hypertension. Here we tested whether long-term AT2R activation affects renal function in obesity using lean and obese Zucker rats treated with the AT2R agonist CGP42112A for 2-weeks. This caused blood pressure to decrease by 13 mmHg which was associated with increased urinary sodium excretion in the obese rats. Cortical ACE2 expression and activity, the Mas receptor (MasR), and its ligand angiotensin-(1-7) were all increased in CGP-treated obese compared with control rats. Candesartan-induced natriuresis, a measure of AT1R function, was reduced but cortical AT1R expression and angiotensin II levels were similar in CGP-treated obese compared to control rats. Renin and AT2R expression in obese rats was not affected by CGP-treatment. In HK-2 cells in-vitro, CGP-treatment caused increased ACE2 activity and MasR levels but decreased AT1R levels and renin activity. Thus, long-term AT2R activation shifts the opposing arms of renin angiotensin system and contributes to natriuresis and blood pressure reduction in obese animals. Our study highlights the importance of AT2R as a target for treating obesity related hypertension. PMID:23823602

  6. Dehydroepiandrosterone decreases serum tumor necrosis factor-alpha and restores insulin sensitivity: independent effect from secondary weight reduction in genetically obese Zucker fatty rats.

    PubMed

    Kimura, M; Tanaka, S; Yamada, Y; Kiuchi, Y; Yamakawa, T; Sekihara, H

    1998-07-01

    Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant circulating adrenal steroids in humans. Administration of DHEA has been reported to have beneficial effects on obesity, hyperlipidemia, diabetes, and atherosclerosis in obese rodents, although its effects on insulin resistance have not been fully elucidated. In this study, the effects of DHEA treatment on insulin sensitivity were investigated in genetically obese Zucker rats, an animal model of insulin resistance, using the euglycemic clamp technique. After 0.4% DHEA was administered for 10 days to female obese Zucker rats aged 16 weeks, body weight and plasma insulin decreased and glucose disposal rate (GDR), which was normally reduced in obese rats, rose significantly compared with age- and sex-matched control obese rats. On the other hand, although the pair-fed obese rats also showed levels of weight reduction similar to those of DHEA-treated rats, the increase in GDR of DHEA-treated rats was significantly greater than in pair-fed rats, suggesting a direct ameliorating effect of DHEA on insulin sensitivity of obese rats. Serum concentration of tumor necrosis factor (TNF)-alpha, one of cytokines causing insulin resistance, was also reduced significantly in DHEA-treated, but not in pair-fed obese rats. In conclusion, our results suggest that DHEA treatment reduces body weight and serum TNF-alpha independently, and that both may ameliorate insulin resistance in obese Zucker fatty rats.

  7. Wild blueberry consumption attenuates local inflammation in the perivascular adipose tissue of obese Zucker rats.

    PubMed

    Vendrame, Stefano; Tsakiroglou, Panagiotis; Kristo, Aleksandra S; Schuschke, Dale A; Klimis-Zacas, Dorothy

    2016-10-01

    Perivascular adipose tissue (PVAT) has been shown to play important roles in regulating vascular tone and linking local and systemic vascular inflammation. We examined the impact of PVAT on phenylephrine-mediated vasoconstriction in the aorta of obese Zucker rats (OZR) and their lean littermates (LZR) by comparing aortic rings with or without PVAT. Subsequently we placed OZR and LZR on a control (C) or an 8% wild blueberry (WB) diet and evaluated the effect of WB consumption on such response. PVAT-released adipokine concentrations were also measured as a function of WB diet. Maximal constrictor force (Fmax) in aortic rings without PVAT was significantly lower in OZR-C compared with LZR-C (0.41 ± 0.05 and 0.71 ± 0.06 g, respectively). Following WB diet, Fmax significantly increased in OZR (0.54 ± 0.06 g). In aortas with intact PVAT, Fmax was significantly lower in all groups (0.31 ± 0.06 OZR-C, 0.30 ± 0.05 OZR-WB, 0.29 ± 0.03 LZR-C, and 0.30 ± 0.04 g LZR-WB), but no difference was observed between treatments. PVAT concentrations of monocyte chemoactractant protein 1 (MCP-1), tumor necrosis factor alpha, and adiponectin were significantly higher in OZR compared with LZR (+102%, +108%, and +45%, respectively). Following WB diet, PVAT concentrations of interleukin-8 were significantly lower in both OZR (-37%) and LZR (-30%), while adiponectin concentrations significantly increased in both OZR (+11%) and LZR (+16%). MCP-1 concentrations significantly decreased (-31%) in the PVAT of OZR with the WB diet. WB consumption appears to attenuate local inflammation in PVAT, which may impact systemic vascular inflammation and endothelial function.

  8. 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.

  9. 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.

  10. Nebivolol Improves Diastolic Dysfunction and Myocardial Remodeling through Reductions in Oxidative Stress in the Zucker Obese Rat

    PubMed Central

    Zhou, Xinli; Ma, Lixin; Habibi, Javad; Whaley-Connell, Adam; Hayden, Melvin R; Tilmon, Roger D; Brown, Ashley N; Kim, Jeong-a; DeMarco, Vincent G.; Sowers, James R

    2010-01-01

    Insulin resistance is associated with obesity and may be accompanied by left ventricular diastolic dysfunction and myocardial remodeling. Decreased insulin metabolic signaling and increased oxidative stress may promote these maladaptive changes. In this context, the β-blocker nebivolol has been reported to improve insulin sensitivity, increase eNOS activity, and reduce NADPH oxidase-induced superoxide generation. We hypothesized that nebivolol would attenuate diastolic dysfunction and myocardial remodeling by blunting myocardial oxidant stress and promoting insulin metabolic signaling in a rodent model of obesity, insulin resistance, and hypertension. Six week old male Zucker obese (ZO) and age-matched Zucker lean (ZL) rats were treated with nebivolol (10 mg·kg−1·day−1) for 21 days and myocardial function was assessed by cine magnetic resonance imaging. Compared to untreated ZL rats, untreated ZO rats exhibited prolonged diastolic relaxation time (27.7±2.5 vs 40.9±2.0 ms; P<0.05) and reduced initial diastolic filling rate (6.2±0.5 vs 2.8±0.6 μl/ms; P<0.05) in conjunction with increased HOMA-IR (7±2 vs 95±21; P<0.05), interstitial and pericapillary fibrosis, abnormal cardiomyocyte histoarchitecture, 3-nitrotyrosine, and NADPH oxidase-dependent superoxide. Nebivolol improved diastolic relaxation (32.8±0.7 ms; P<0.05 vs untreated ZO), reduced fibrosis and remodeling in ZO rats, in concert with reductions in nitrotyrosine, NADPH oxidase-dependent superoxide, and improvements in the insulin metabolic signaling, eNOS activation, and weight gain (381±7 vs 338±14 g; P<0.05). Results support the hypothesis that nebivolol reduces myocardial structural maladaptive changes and improves diastolic relaxation in concert with improvements in insulin sensitivity, and eNOS activation, concomitantly with reductions in oxidative stress. PMID:20176997

  11. The effects of treadmill exercise on expression of UCP-2 of brown adipose tissue and TNF-α of soleus muscle in obese Zucker rats

    PubMed Central

    Kim, Dong-Hee; Kim, Seok-Hwan; Kim, Won-Hee; Moon, Chae-Ryen

    2013-01-01

    Sorts of abnormal state, obesity and inflammation are involved in a number of serious disease occurring and both of them became important research topics among molecular biologists. UCP-2 and TNF-α respectively reflecting obese and inflammatory status have often been used to evaluate the effects of independent variable, such as exercise, on them. Because exercise has shown its potent control on obesity and inflammation, it is necessary to determine if exercise is working via same bioindices. The purpose of this study was to determine the effects of different treadmill exercise intensities on UCP-2 of brown adipose tissue and TNF-α of soleus muscle during 8 weeks in Zucker rat. Zucker rats were divided into four groups (n = 7 in each group): control group, low intensity exercise group, moderate intensity exercise group and high intensity exercise group. Zucker rats of the exercise groups were made to run on a motorized treadmill for 30 minutes once a day during 8 weeks. Rats were sacrificed 24 hours after the last bout of exercise. Blood glucose in Zucker rats were measured by Gluco-Card Ⅱ. Brown adipose tissue were extracted to analyze the level of UCP-2 and TNF-α, respectively. UCP-2 and TNF-α were analyzed using the Western Blotting technique. Statistical techniques for data analysis were repeated measure ANOVA and one way ANOVA to determine the difference between groups, and for post hoc test was Duncan' test. The 5% level of significance was utilized as the critical level for acceptance of hypotheses for the study. The following results were obtained from this study; UCP-2 protein expression of brown adipose tissue in Zucker rats were increased significantly following exercise of the low and moderate intensities compared to those of control group after 8 weeks. It was shown that TNF-α protein expression of soleus muscle in Zucker rats were decreased significantly following exercise of the low and moderate intensities compared to those of control group

  12. 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.

  13. Oxidative Stress Causes Imbalance of Renal Renin Angiotensin System (RAS) Components and Hypertension in Obese Zucker Rats

    PubMed Central

    Luo, Hao; Wang, Xinquan; Chen, Caiyu; Wang, Jialiang; Zou, Xue; Li, Chuanwei; Xu, Zaicheng; Yang, Xiaoli; Shi, Weibin; Zeng, Chunyu

    2015-01-01

    Background Oxidative stress plays an important role in the pathogenesis of hypertension, especially in obesity‐related hypertension. The natriuretic and antinatriuretic components of the renal renin angiotensin system (RAS) maintain sodium homeostasis and blood pressure. Here, we test the hypothesis that increased oxidative stress leads to the imbalance of RAS components and hypertension in obese Zucker rats. Methods and Results Lean and obese rats received vehicle or tempol, a superoxide dismutase mimetic in the drinking water for 4 weeks. Compared with vehicle‐treated lean rats, vehicle‐treated obese rats exhibited higher blood pressure and increased renal oxidative stress, accompanied by increased diuretic and natriuretic responses to AT1R antagonist (Candesartan) and AT2R agonist (CGP‐42112A) and reduced diuretic and natriuretic response to MasR agonist (Ang‐[1 to 7]). Moreover, obese rats had higher ACE, AT1R and AT2R, lower ACE2 and MasR expressions in the kidney. All of the above‐mentioned abnormalities were reversed to some degree by tempol treatment. In primary cultures of renal proximal tubular (RPT) cells from lean and obese rats, tempol treatment also increased AT2R, ACE2, and MasR expressions but decreased AT1R and ACE expressions in obese rats. Conclusions Taken together, our study indicated that the imbalance of renal RAS components was associated with increased oxidative stress in obese rats. Furthermore, antioxidant treatment with tempol reversed the imbalance of renal RAS components and led to diuresis and natriuresis, which, at least in part, explains the blood pressure‐lowering effect of antioxidant supplementation in obesity‐related hypertension. PMID:25687731

  14. Treatment with a novel oleic-acid-dihydroxyamphetamine conjugation ameliorates non-alcoholic fatty liver disease in obese Zucker rats.

    PubMed

    Decara, Juan M; Pavón, Francisco Javier; Suárez, Juan; Romero-Cuevas, Miguel; Baixeras, Elena; Vázquez, Mariam; Rivera, Patricia; Gavito, Ana L; Almeida, Bruno; Joglar, Jesús; de la Torre, Rafael; Rodríguez de Fonseca, Fernando; Serrano, Antonia

    2015-10-01

    Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no effective treatments for this pathology apart from the use of classical fibrates. In this study, we have characterized the in vivo effects of a novel conjugation of oleic acid with an amphetamine derivative (OLHHA) in an animal model of genetic obesity. Lean and obese Zucker rats received a daily intraperitoneal administration of OLHHA (5 mg kg(-1)) for 15 days. Plasma and liver samples were collected for the biochemical and molecular biological analyses, including both immunohistochemical and histological studies. The expression of key enzymes and proteins that are involved in lipid metabolism and energy homeostasis was evaluated in the liver samples. The potential of OLHHA to produce adverse drug reactions or toxicity was also evaluated through the monitoring of interactions with hERG channel and liver cytochrome. We found that OLHHA is a drug with a safe pharmacological profile. Treatment for 15 days with OLHHA reduced the liver fat content and plasma triglyceride levels, and this was accompanied by a general improvement in the profile of plasma parameters related to liver damage in the obese rats. A decrease in fat accumulation in the liver was confirmed using histological staining. Additionally, OLHHA was observed to exert anti-apoptotic effects. This hepatoprotective activity in obese rats was associated with an increase in the mRNA and protein expression of the cannabinoid type 1 receptor and a decrease in the expression of the lipogenic enzymes FAS and HMGCR primarily. However, changes in the mRNA expression of certain proteins were not associated with changes in the protein expression (i.e. L-FABP and INSIG2). The present results demonstrate that OLHHA is a potential anti-steatotic drug that ameliorates the obesity-associated fatty liver and suggest the potential use of this new drug for the treatment of non-alcoholic fatty liver disease.

  15. Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects.

    PubMed

    Hijona, E; Aguirre, L; Pérez-Matute, P; Villanueva-Millán, M J; Mosqueda-Solis, A; Hasnaoui, M; Nepveu, F; Senard, J M; Bujanda, L; Aldámiz-Echevarría, L; Llarena, M; Andrade, F; Perio, P; Leboulanger, F; Hijona, L; Arbones-Mainar, J M; Portillo, M P; Carpéné, C

    2016-09-01

    Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.

  16. Brain glucose overexposure and lack of acute metabolic flexibility in obesity and type 2 diabetes: a PET-[18F]FDG study in Zucker and ZDF rats.

    PubMed

    Liistro, Tiziana; Guiducci, Letizia; Burchielli, Silvia; Panetta, Daniele; Belcari, Nicola; Pardini, Silvia; Del Guerra, Alberto; Salvadori, Piero A; Iozzo, Patricia

    2010-05-01

    Brain glucose exposure may complicate diabetes and obesity. We used positron emission tomography with (18)F-fluorodeoxyglucose in Zucker obese, diabetic, and control rats to determine the contributions of blood glucose mass action versus local mechanisms in regulating central glucose disposal in fasted and acutely glucose-stimulated states, and their adaptations in obesity and diabetes. Our study data indicate that brain glucose uptake is dependent on both local and mass action components, and is stimulated by acute glucose intake in healthy rats. In diseased animals, the organ was chronically overexposed to glucose, due to high fasting glucose uptake, almost abolishing the physiologic response to glucose loading.

  17. Serum lipids, lipoprotein composition and liver cholesterol in genetically obese Zucker rats fed semipurified diets containing either casein or soy protein.

    PubMed

    Terpstra, A H; van Tintelen, G; West, C E

    1983-01-01

    The effect of semipurified diets containing either casein or soy protein on serum lipids, lipoprotein composition and liver cholesterol was studied in genetically obese Zucker rats. The ingestion of a cholesterol-enriched semipurified diet containing casein resulted in elevated levels of serum cholesterol and phospholipids compared to the feeding of a soy protein diet. No differences in serum triglycerides were observed. Differences in serum cholesterol and phospholipids were mainly reflected in the very low density lipoproteins and low density lipoproteins and to a minor extent in the high density lipoproteins. Liver cholesterol paralleled the levels of cholesterol in the serum, the rats fed casein exhibited markedly higher levels of liver cholesterol than those fed soy protein. Furthermore, the rats fed casein also had enlarged livers. Thus, this study clearly shows the differential cholesterolemic effect of dietary casein and soy protein in genetically obese Zucker rats.

  18. Effect of insulin and contraction on glycogen synthase phosphorylation and kinetic properties in epitrochlearis muscles from lean and obese Zucker rats.

    PubMed

    Lin, Fang Chin; Bolling, Astrid; Stuenæs, Jorid T; Cumming, Kristoffer T; Ingvaldsen, Ada; Lai, Yu-Chiang; Ivy, John L; Jensen, Jørgen

    2012-05-15

    In the present study, the effects of insulin and contraction on glycogen synthase (GS) kinetic properties and phosphorylation were investigated in epitrochlearis muscles from lean and obese Zucker rats. Total GS activity and protein expression were ~15% lower in epitrochlearis from obese rats compared with lean rats. Insulin-stimulated GS fractional activity and affinity for UDP-glucose were lower (higher K(m)) in muscles from obese rats. GS Ser(641) and Ser(645,649,653,657) phosphorylation was higher in insulin-stimulated muscles from obese rats, which agreed with lower GS activation. Contraction-mediated GS dephosphorylation of Ser(641), Ser(641+645), Ser(645,649,653,657), and Ser(7+10) was normal in muscles from obese Zucker rats, and GS fractional activity increased to similar levels in epitrochlearis muscles from lean and obese rats. GS affinity for UDP glucose was ~0.8, ~0.4, and ~0.1 mM with assay buffers containing 0, 0.17, and 12 mM glucose 6-phosphate, respectively. Contraction increased affinity for UDP-glucose (reduced K(m)) at a physiological concentration of glucose 6-phosphate (0.17 mM) to ~0.2 mM in muscles from both lean and obese rats. Interestingly, in the absence of glucose 6-phosphate in the assay buffer, contraction (and insulin) did not influence GS affinity for UDP-glucose, indicating that affinity is regulated by sensitivity for glucose 6-phosphate. In conclusion, contraction-mediated activation and dephosphorylation of GS were normal in muscles from obese Zucker rats, whereas insulin-mediated GS activation and dephosphorylation were impaired.

  19. Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension.

    PubMed

    Goodwill, Adam G; James, Milinda E; Frisbee, Jefferson C

    2008-10-01

    This study determined if altered vascular prostacyclin (PGI(2)) and/or thromboxane A(2) (TxA(2)) production with reduced Po(2) contributes to impaired hypoxic dilation of skeletal muscle resistance arterioles of obese Zucker rats (OZRs) versus lean Zucker rats (LZRs). Mechanical responses were assessed in isolated gracilis muscle arterioles following reductions in Po(2) under control conditions and following pharmacological interventions inhibiting arachidonic acid metabolism and nitric oxide synthase and alleviating elevated vascular oxidant stress. The production of arachidonic acid metabolites was assessed using pooled arteries from OZRs and LZRs in response to reduced Po(2). Hypoxic dilation, endothelium-dependent in both strains, was attenuated in OZRs versus LZRs. Nitric oxide synthase inhibition had no significant impact on hypoxic dilation in either strain. Cyclooxygenase inhibition dramatically reduced hypoxic dilation in LZRs and abolished responses in OZRs. Treatment of arterioles from OZRs with polyethylene glycol-superoxide dismutase improved hypoxic dilation, and this improvement was entirely cyclooxygenase dependent. Vascular PGI(2) production with reduced Po(2) was similar between strains, although TxA(2) production was increased in OZRs, a difference that was attenuated by treatment of vessels from OZRs with polyethylene glycol-superoxide dismutase. Both blockade of PGH(2)/TxA(2) receptors and inhibition of thromboxane synthase increased hypoxic dilation in OZR arterioles. These results suggest that a contributing mechanism underlying impaired hypoxic dilation of skeletal muscle arterioles of OZRs may be an increased vascular production of TxA(2), which competes against the vasodilator influences of PGI(2). These results also suggest that the elevated vascular oxidant stress inherent in metabolic syndrome may contribute to the increased vascular TxA(2) production and may blunt vascular sensitivity to PGI(2).

  20. Renal angiotensin II type-2 receptors are upregulated and mediate the candesartan-induced natriuresis/diuresis in obese Zucker rats.

    PubMed

    Hakam, Amer C; Hussain, Tahir

    2005-02-01

    Recently, there has been a growing interest in studying the role of angiotensin II type-2 (AT(2)) receptor in renal/cardiovascular function in pathological conditions. The present study was designed to determine the functional role of the AT(2) receptors on natriuresis/diuresis and compare the level of the tubular AT(2) receptor expression in obese and lean Zucker rats (12 weeks old). Under anesthesia, candesartan (angiotensin II type 1 [AT(1)]-specific antagonist; 100 microg/kg bolus) produced natriuresis/diuresis to a greater degree in obese than in lean rats. The specific AT(2) antagonist PD123319 (50 microg/kg per minute) after candesartan administration abolished the natriuretic/diuretic effects of candesartan in obese rats but not in lean rats. Infusion of AT(2) receptor agonist, CGP-42112A (1 microg/kg per minute), produced greater increase in sodium and urine excretion over basal in obese than in lean rats. The presence of the AT(2) receptor expression in the brush-border and basolateral membranes was confirmed by Western blotting using specific antibody and antigen-blocking peptide. Densitometric analysis of the bands revealed approximately 1.5- to 2.0-fold increase in the AT(2) receptor proteins in both membranes of obese compared with lean rats. Our results suggest upregulation of the AT(2) receptors, which play a role in mediating the natriuretic/diuretic effects of AT(1) receptor blockers in obese Zucker rats. We speculate that AT(2) receptors, by promoting sodium excretion, may protect obese Zucker rats against blood pressure increase associated with sodium and water retention.

  1. Pharmacological evaluation of a β-hydroxyphosphonate analogue of l-carnitine in obese Zucker fa/fa rats.

    PubMed

    Reyes-Esparza, Jorge; Mendoza-Rivera, Brissa; De la Cruz-Cordero, Ricardo; Rosado, Jorge L; Duarte-Vázquez, Miguel Á; Solis, Mario G; Vite-Vallejo, Odón; Rodríguez-Fragoso, Lourdes

    2013-04-01

    In this study, we evaluated the effect of an analogue of l-carnitine on parameters involved with Metabolic Syndrome in obese Zucker rats. Twenty-four rats were treated for 5 weeks with l-carnitine (300 mg/kg) and its analogue at two concentrations (100 and 250 mg/kg) to assess their impact on glucose, triglycerides and cholesterol in liver and blood samples, as well as the amount of liver glycogen. Liver slices were also analysed. The analogue reduced the levels of glucose, triglycerides and cholesterol in liver and the level of triglycerides in serum. At 100 mg/kg, the analogue proved more effective than l-carnitine in improving the biochemical alterations present in liver. The amount of liver glycogen content was higher in obese animals treated with both l-carnitine and the analogue. No changes on insulin and leptin were observed in animals treated. l-carnitine and its analogue reduced the microvesicular fatty infiltration in liver. This study demonstrated that the analogue tested is more potent and efficient than l-carnitine and improves the pharmacological profile of l-carnitine.

  2. Diminished Neurogenic Femoral Artery Vasoconstrictor Response in a Zucker Obese Rat Model: Differential Regulation of NOS and COX Derivatives

    PubMed Central

    Martínez, Ana Cristina; Hernández, Medardo; Novella, Susana; Martínez, María Pilar; Pagán, Rosa María; Hermenegildo, Carlos; García-Sacristán, Albino; Prieto, Dolores; Benedito, Sara

    2014-01-01

    Objective Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR) by examining cross-talk between endothelial and neural factors. Methods and Results Arterial preparations from lean (LZR) and OZR were subjected to electrical field stimulation (EFS) on basal tone. Nitric oxide synthase (NOS) and cyclooxygenase (COX) isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS) indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS) and inducible NOS (iNOS) were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by large-conductance Ca2+-activated (BKCa) or voltage-dependent (KV) K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR. Conclusions Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation. PMID:25216050

  3. Treatment with a novel oleic-acid–dihydroxyamphetamine conjugation ameliorates non-alcoholic fatty liver disease in obese Zucker rats

    PubMed Central

    Decara, Juan M.; Pavón, Francisco Javier; Suárez, Juan; Romero-Cuevas, Miguel; Baixeras, Elena; Vázquez, Mariam; Rivera, Patricia; Gavito, Ana L.; Almeida, Bruno; Joglar, Jesús; de la Torre, Rafael; Rodríguez de Fonseca, Fernando; Serrano, Antonia

    2015-01-01

    ABSTRACT Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no effective treatments for this pathology apart from the use of classical fibrates. In this study, we have characterized the in vivo effects of a novel conjugation of oleic acid with an amphetamine derivative (OLHHA) in an animal model of genetic obesity. Lean and obese Zucker rats received a daily intraperitoneal administration of OLHHA (5 mg kg−1) for 15 days. Plasma and liver samples were collected for the biochemical and molecular biological analyses, including both immunohistochemical and histological studies. The expression of key enzymes and proteins that are involved in lipid metabolism and energy homeostasis was evaluated in the liver samples. The potential of OLHHA to produce adverse drug reactions or toxicity was also evaluated through the monitoring of interactions with hERG channel and liver cytochrome. We found that OLHHA is a drug with a safe pharmacological profile. Treatment for 15 days with OLHHA reduced the liver fat content and plasma triglyceride levels, and this was accompanied by a general improvement in the profile of plasma parameters related to liver damage in the obese rats. A decrease in fat accumulation in the liver was confirmed using histological staining. Additionally, OLHHA was observed to exert anti-apoptotic effects. This hepatoprotective activity in obese rats was associated with an increase in the mRNA and protein expression of the cannabinoid type 1 receptor and a decrease in the expression of the lipogenic enzymes FAS and HMGCR primarily. However, changes in the mRNA expression of certain proteins were not associated with changes in the protein expression (i.e. L-FABP and INSIG2). The present results demonstrate that OLHHA is a potential anti-steatotic drug that ameliorates the obesity-associated fatty liver and suggest the potential use of this new drug for the treatment of non-alcoholic fatty liver

  4. Acyl-CoA binding protein expression is fiber type- specific and elevated in muscles from the obese insulin-resistant Zucker rat.

    PubMed

    Franch, Jesper; Knudsen, Jens; Ellis, Bronwyn A; Pedersen, Preben K; Cooney, Gregory J; Jensen, Jørgen

    2002-02-01

    Accumulation of acyl-CoA is hypothesized to be involved in development of insulin resistance. Acyl-CoA binds to acyl-CoA binding protein (ACBP) with high affinity, and therefore knowledge about ACBP concentration is important for interpreting acyl-CoA data. In the present study, we used a sandwich enzyme-linked immunosorbent assay to quantify ACBP concentration in different muscle fiber types. Furthermore, ACBP concentration was compared in muscles from lean and obese Zucker rats. Expression of ACBP was highest in the slow-twitch oxidative soleus muscle and lowest in the fast-twitch glycolytic white gastrocnemius (0.46 +/- 0.02 and 0.16 +/- 0.005 microg/mg protein, respectively). Expression of ACBP was soleus > red gastrocnemius > extensor digitorum longus > white gastrocnemius. Similar fiber type differences were found for carnitine palmitoyl transferase (CPT)-1, and a correlation was observed between ACBP and CPT-1. Muscles from obese Zucker rats had twice the triglyceride content, had approximately twice the long-chain acyl CoA content, and were severely insulin resistant. ACBP concentration was approximately 30% higher in all muscles from obese rats. Activities of CPT-1 and 3-hydroxy-acyl-CoA dehydrogenase were increased in muscles from obese rats, whereas citrate synthase activity was similar. In conclusion, ACBP expression is fiber type-specific with the highest concentration in oxidative muscles and the lowest in glycolytic muscles. The 90% increase in the concentration of acyl-CoA in obese Zucker muscle compared with only a 30% increase in the concentration of ACBP supports the hypothesis that an increased concentration of free acyl-CoA is involved in the development of insulin resistance.

  5. Immunohistochemical localization of CB1 cannabinoid receptors in frontal cortex and related limbic areas in obese Zucker rats: effects of chronic fluoxetine treatment.

    PubMed

    Zarate, J; Churruca, I; Echevarría, E; Casis, L; López de Jesús, M; Saenz del Burgo, L; Sallés, J

    2008-10-21

    In the present study, we report on the application of two specific polyclonal antibodies to different intracellular domains of the CB1 cannabinoid receptor to define the expression of the neural CB1 cannabinoid receptor at the histochemical level in frontal cortex and related limbic areas of the obese Zucker rats. Higher levels of CB1 receptor expression in frontal, cingulated and piriform cortex, without differences in temporal, parietal and occipital cortex, were observed in obese Zucker rats, with respect to their lean littermates. CB1 phosphorylated receptor (CB1-P) levels were also higher in frontal, temporal, parietal and occipital cortex in obese rats with respect to lean controls. Potential involvement of brain cortical CB1 cannabinoid receptors in the long-term effects of fluoxetine was studied. Experimental animals were administered with fluoxetine (10 mg/kg, i.p.) daily for 3 weeks, whereas the control group was given 0.9% NaCl solution. In obese Zucker rats, a significant decrease in CB1 receptor levels, measured by western blot, was observed in brain cortex after fluoxetine treatment. Immunostaining for CB1 receptor expression was also carried out, showing a significant decrease in the density of neural cells positive for CB1 receptor in frontal, cingulate and piriform cortex, without changes in parietal, temporal and occipital regions. Regional prosencephalic immunostaining for CB1-P receptor level showed a significant decrease in the density of stained neural cells in frontal, temporal and parietal cortex, without changes in cingulated, piriform and occipital cortex. These results suggest the involvement of endocannabinoid system in the chronic effects of fluoxetine, especially in the frontal cortex.

  6. 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.

  7. The age estimation of blood stains up to 30 days old using visible wavelength hyperspectral image analysis and linear discriminant analysis.

    PubMed

    Li, Bo; Beveridge, Peter; O'Hare, William T; Islam, Meez

    2013-09-01

    A novel application of visible wavelength hyperspectral image analysis has been applied to determine the age of blood stains up to 30 days old. Reflectance spectra from selected locations within the hyperspectral image, obtained from a portable instrument, were subjected to spectral pre-processing. This was followed by the application of a linear discriminant classification model, making estimations possible with an average error of ±0.27days for the first 7 days and an overall average error of ±1.17days up to 30 days. This is also the first reported study of the determination of the age of fresh blood stains (less than one day old) with an error of ±0.09h. The studies have been made under controlled conditions and represent, at this stage, proof of concept results but also are the most accurate age estimation results for measurements between 0 and 30 days reported to date. The results are consistent with well-established kinetic processes suggesting that the pre-processing stages described are revealing spectroscopic changes which are reliably following the time dependent oxidation of HbO2. The potential for parameterisation of environmental factors to make the method generally applicable at crime scenes is discussed, along with the developments required to further improve classification and to make the instrument genuinely portable.

  8. Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats.

    PubMed

    Asghar, Mohammad; Monjok, Emmanuel; Kouamou, Ghislaine; Ohia, Sunny E; Bagchi, Debasis; Lokhandwala, Mustafa F

    2007-10-01

    Super CitriMax (HCA-SX) is a novel calcium/potassium salt of (-)-hydroxycitric acid extracted from the dried fruit rind of the plant Garcinia cambogia, and commonly consumed as weight loss dietary supplement. In the present study, we investigated the effect of HCA-SX on inflammation, oxidative stress and insulin resistance in developing obese Zucker rats, an animal model of type II diabetes associated with inflammation and oxidative stress. Male Zucker rats (5-week old) were supplemented with vehicle (control) and HCA-SX in drinking water for 7 weeks. Oxidative stress markers, including malondialdehyde (MDA), protein carbonyl (DNPH), and protein tyrosine nitration (tyr-NO(2)) were measured in the liver and kidney tissues using biochemical and immunoblotting techniques. Compared to controls, the levels of MDA, DNPH and tyr-NO(2) were lower in the liver and kidney of HCA-SX-treated animals. Furthermore, the levels of C-reactive protein and interleukin-6, markers of inflammation measured by ELISA, were lower in the plasma of HCA-SX-supplemented animals compared to controls, as were levels of fasting plasma insulin, glucose, and triglycerides. Interestingly, insulin resistance did not develop in HCA-SX-supplemented rats. Food-intake and body weight gain was also lower in rats supplemented with HCA-SX compared to their control counterparts. These results suggest that HCA-SX supplementation in obese Zucker rats reduces food-intake, body weight gain, and also attenuates the increases in inflammation, oxidative stress, and insulin resistance observed in untreated animals. Therefore, HCA-SX may be used as an intervention to overcome obesity-related complications, including inflammation, oxidative stress, and insulin resistance.

  9. Chronic AT2 receptor activation increases renal ACE2 activity, attenuates AT1 receptor function and blood pressure in obese Zucker rats.

    PubMed

    Ali, Quaisar; Wu, Yonnie; Hussain, Tahir

    2013-11-01

    Abnormal regulation of the renin angiotensin system such as enhanced renal AT1R function and reduced ACE2 activity contributes to obesity-related hypertension. Here, we tested whether long-term AT2R activation affects renal function in obesity using lean and obese Zucker rats treated with the AT2R agonist CGP42112A for 2 weeks. This caused blood pressure to decrease by 13 mm Hg, which was associated with increased urinary sodium excretion in the obese rats. Cortical ACE2 expression and activity, the Mas receptor (MasR), and its ligand angiotensin-(1-7) were all increased in CGP-treated obese compared with control rats. Candesartan-induced natriuresis, a measure of AT₁R function, was reduced but cortical AT₁R expression and angiotensin II levels were similar in CGP-treated obese compared with control rats. Renin and AT2R expression in obese rats was not affected by CGP treatment. In HK-2 cells in vitro, CGP treatment caused increased ACE2 activity and MasR levels but decreased AT₁R levels and renin activity. Thus, long-term AT2R activation shifts the opposing arms of renin angiotensin system and contributes to natriuresis and blood pressure reduction in obese animals. Our study highlights the importance of AT2R as a target for treating obesity-related hypertension.

  10. Mild caloric restriction reduces blood pressure and activates endothelial AMPK-PI3K-Akt-eNOS pathway in obese Zucker rats.

    PubMed

    García-Prieto, C F; Pulido-Olmo, H; Ruiz-Hurtado, G; Gil-Ortega, M; Aranguez, I; Rubio, M A; Ruiz-Gayo, M; Somoza, B; Fernández-Alfonso, M S

    2015-01-01

    Genetic obesity models exhibit endothelial dysfunction associated to adenosine monophosphate-activated protein kinase (AMPK) dysregulation. This study aims to assess if mild short-term caloric restriction (CR) restores endothelial AMPK activity leading to an improvement in endothelial function. Twelve-week old Zucker lean and obese (fa/fa) male rats had access to standard chow either ad libitum (AL, n=8) or 80% of AL (CR, n=8) for two weeks. Systolic blood pressure was significantly higher in fa/fa AL rats versus lean AL animals, but was normalized by CR. Endothelium-dependent relaxation to acetylcholine (ACh, 10(-9) to 10(-4) M) was reduced in fa/fa AL compared to control lean AL rats (p<0.001), and restored by CR. The AMPK activator AICAR (10(-5) to 8·10(-3) M) elicited a lower relaxation in fa/fa AL rings that was normalized by CR (p<0.001). Inhibition of PI3K (wortmannin, 10(-7) M), Akt (triciribine, 10(-5) M), or eNOS (L-NAME, 10(-4) M) markedly reduced AICAR-induced relaxation in lean AL, but not in fa/fa AL rats. These inhibitions were restored by CR in Zucker fa/fa rings. These data show that mild short-term CR improves endothelial function and lowers blood pressure in obesity due to the activation of the AMPK-PI3K-Akt-eNOS pathway.

  11. Dietary CLA combined with palm oil or ovine fat differentially influences fatty acid deposition in tissues of obese Zucker rats.

    PubMed

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

    2012-01-01

    The effect of dietary conjugated linoleic acid (CLA) supplementation in combination with fat from vegetable versus animal origin on the fatty acid deposition, including that of individual 18:1 and 18:2 (conjugated and non-conjugated) isomers, in the liver and muscle of obese rats was investigated. For this purpose, 32 male Zucker rats were randomly assigned to one of four diets containing palm oil or ovine fat, supplemented or not with 1% of 1:1 cis(c)9,trans(t)11 and t10,c12 CLA isomers mixture. Total fatty acid content decreased in the liver and muscle of CLA-fed rats. In the liver, CLA increased saturated fatty acids (SFA) in 11.9% and decreased monounsaturated fatty acids (MUFA) in 6.5%. n-3 Polyunsaturated fatty acids (PUFA) relative proportions were increased in 30.6% by CLA when supplemented to the ovine fat diet. In the muscle, CLA did not affect SFA but decreased MUFA and PUFA percentages. The estimation of Δ9-indices 16 and 18 suggested that CLA inhibited the stearoyl-CoA desaturase activity in the liver (a decrease of 13-38%), in particular when supplemented to the ovine fat diet. Concerning CLA supplementation, the t10,c12 isomer percentage was 60-80% higher in the muscle than in the liver. It is of relevance that rats fed ovine fat, containing bio-formed CLA, had more c9,t11 CLA isomer deposited in both tissues than rats fed palm oil plus synthetic CLA. These results highlight the importance to further clarify the biological effects of consuming foods naturally enriched in CLA, alternatively to CLA dietary supplementation.

  12. 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.

  13. Upregulation of SK3 and IK1 Channels Contributes to the Enhanced Endothelial Calcium Signaling and the Preserved Coronary Relaxation in Obese Zucker Rats

    PubMed Central

    Climent, Belén; Moreno, Laura; Martínez, Pilar; Contreras, Cristina; Sánchez, Ana; Pérez-Vizcaíno, Francisco; García-Sacristán, Albino; Rivera, Luis; Prieto, Dolores

    2014-01-01

    Background and Aims Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO) release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals. Methods and Results In coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR) compared to Lean Zucker Rats (LZR). Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer. Conclusions Obesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity. PMID:25302606

  14. Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese Zucker rats

    PubMed Central

    Ali, Quaisar; Patel, Sanket

    2015-01-01

    High-sodium intake is a risk factor for the pathogenesis of hypertension, especially in obesity. The present study is designed to investigate whether angiotensin type 2 receptor (AT2R) activation with selective agonist C21 prevents high-sodium diet (HSD)-induced hypertension in obese animals. Male obese rats were treated with AT2R agonist C21 (1 mg·kg−1·day−1, oral) while maintained on either normal-sodium diet (NSD; 0.4%) or HSD (4%) for 2 wk. Radiotelemetric recording showed a time-dependent increase in systolic blood pressure in HSD-fed obese rats, being maximal increase (∼27 mmHg) at day 12 of the HSD regimen. C21 treatment completely prevented the increase in blood pressure of HSD-fed rats. Compared with NSD controls, HSD-fed obese rats had greater natriuresis/diuresis and urinary levels of nitrates, and these parameters were further increased by C21 treatment. Also, C21 treatment improved glomerular filtration rate in HSD-fed rats. HSD-fed rats expressed higher level of cortical ANG II, which was reduced to 50% by C21 treatment. HSD feeding and/or C21 treatment had no effects on cortical renin activity and the expression of angiotensin-converting enzyme (ACE) and chymase, which are ANG II-producing enzymes. However, ANG(1–7) concentration and ACE2 activity in the renal cortex were reduced by HSD feeding, and C21 treatment rescued both the parameters. Also, C21 treatment reduced the cortical expression of AT1R in HSD-fed rats, but had no effect of AT2R expression. We conclude that chronic treatment with the AT2R agonist C21 prevents salt-sensitive hypertension in obese rats, and a reduction in the renal ANG II/AT1R and enhanced ACE2/ANG(1–7) levels may play a potential role in this phenomenon. PMID:25855512

  15. Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese Zucker rats.

    PubMed

    Ali, Quaisar; Patel, Sanket; Hussain, Tahir

    2015-06-15

    High-sodium intake is a risk factor for the pathogenesis of hypertension, especially in obesity. The present study is designed to investigate whether angiotensin type 2 receptor (AT2R) activation with selective agonist C21 prevents high-sodium diet (HSD)-induced hypertension in obese animals. Male obese rats were treated with AT2R agonist C21 (1 mg·kg(-1)·day(-1), oral) while maintained on either normal-sodium diet (NSD; 0.4%) or HSD (4%) for 2 wk. Radiotelemetric recording showed a time-dependent increase in systolic blood pressure in HSD-fed obese rats, being maximal increase (∼27 mmHg) at day 12 of the HSD regimen. C21 treatment completely prevented the increase in blood pressure of HSD-fed rats. Compared with NSD controls, HSD-fed obese rats had greater natriuresis/diuresis and urinary levels of nitrates, and these parameters were further increased by C21 treatment. Also, C21 treatment improved glomerular filtration rate in HSD-fed rats. HSD-fed rats expressed higher level of cortical ANG II, which was reduced to 50% by C21 treatment. HSD feeding and/or C21 treatment had no effects on cortical renin activity and the expression of angiotensin-converting enzyme (ACE) and chymase, which are ANG II-producing enzymes. However, ANG(1-7) concentration and ACE2 activity in the renal cortex were reduced by HSD feeding, and C21 treatment rescued both the parameters. Also, C21 treatment reduced the cortical expression of AT1R in HSD-fed rats, but had no effect of AT2R expression. We conclude that chronic treatment with the AT2R agonist C21 prevents salt-sensitive hypertension in obese rats, and a reduction in the renal ANG II/AT1R and enhanced ACE2/ANG(1-7) levels may play a potential role in this phenomenon.

  16. 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.

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

    PubMed

    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.

  18. 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

  19. The effects of wild blueberry consumption on plasma markers and gene expression related to glucose metabolism in the obese Zucker rat.

    PubMed

    Vendrame, Stefano; Zhao, Alice; Merrow, Thomas; Klimis-Zacas, Dorothy

    2015-06-01

    Impaired fasting blood glucose is one of the landmark signs of metabolic syndrome, together with hyperinsulinemia, dyslipidemia, hypertension, and a chronic proinflammatory, pro-oxidative, and prothrombotic environment. This study investigates the effect of wild blueberry (WB) consumption on blood glucose levels and other parameters involved in glucose metabolism in the obese Zucker rat (OZR), an experimental model of metabolic syndrome. Sixteen OZRs and 16 lean littermate controls (lean Zucker rat [LZR]) were fed an 8% enriched WB diet or a control (C) diet for 8 weeks. Plasma concentrations of glucose, insulin, glycated hemoglobin GHbA1c, resistin, and retinol-binding protein 4 (RBP4) were measured. Expression of the resistin, RBP4, and glucose transporter GLUT4 genes was also determined both in the liver and the abdominal adipose tissue (AAT). Plasma glycated hemoglobin HbA1c, RBP4, and resistin concentrations were significantly lower in OZRs following the WB diet (-20%, -22%, and -27%, respectively, compared to C diet, P<.05). Following WB consumption, resistin expression was significantly downregulated in the liver of both OZRs and LZRs (-28% and -61%, respectively, P<.05), while RBP4 expression was significantly downregulated in the AAT of both OZRs and LZRs (-87% and -43%, respectively, P<.05). All other markers were not significantly affected following WB consumption. In conclusion, WB consumption normalizes some markers related to glucose metabolism in the OZR model of metabolic syndrome, but has no effect on fasting blood glucose or insulin concentrations.

  20. A water-alcohol extract of Citrus grandis whole fruits has beneficial metabolic effects in the obese Zucker rats fed with high fat/high cholesterol diet.

    PubMed

    Raasmaja, Atso; Lecklin, Anne; Li, Xiang Ming; Zou, Jianqiang; Zhu, Guo-Guang; Laakso, Into; Hiltunen, Raimo

    2013-06-01

    Epidemiological studies suggest that citrus fruits and compounds such as flavonoids, limonoids and pectins have health promoting effects. Our aim was to study the effects of Citrus grandis (L.) Osbeck var. tomentosa hort. fruit extract on the energy metabolism. A whole fruit powder from dry water and alcohol extracts of C. grandis containing 19% naringin flavonoid was prepared. The effects of the citrus extract were followed in the obese Zucker rats fed with the HFD. The circulatory levels of GLP-1 decreased significantly by the extract in comparison to the HFD group, whereas the decreased ghrelin levels were reversed. The levels of PYY were decreased in all HFD groups. The leptin amounts decreased but not significantly whereas insulin and amylin were unchanged. The cholesterol and glucose levels were somewhat but not systematically improved in the HFD fed rats. Further studies are needed to identify the active compounds and their mechanisms.

  1. 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.

  2. 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.

  3. Altered arachidonic acid metabolism via COX-1 and COX-2 contributes to the endothelial dysfunction of penile arteries from obese Zucker rats

    PubMed Central

    Sánchez, A; Contreras, C; Villalba, N; Martínez, P; Martínez, AC; Bríones, A; Salaíces, M; García-Sacristán, A; Hernández, M; Prieto, D

    2010-01-01

    Background and purpose: The aim of the current study was to investigate the role of arachidonic acid (AA) metabolism via cyclooxygenase (COX) in the endothelial dysfunction of penile arteries from pre-diabetic, obese Zucker rats (OZR). Experimental approach: Penile arteries from OZR and from lean Zucker rats (LZR) were mounted in microvascular myographs to assess vascular function and COX expression was determined by immunohistochemistry. Key results: Acetylcholine (ACh) and AA elicited relaxations that were impaired in arteries from OZR. Inhibition of both COX-1 and COX-2 reduced the relaxant effects of ACh and AA in LZR but not in OZR. Inhibitors of COX-1 and of the TXA2/PGH2 (TP) receptor enhanced the relaxations induced by AA in both LZR and OZR, whereas COX-2 inhibition enhanced these responses only in OZR. TP receptor blockade did not restore ACh relaxant responses in arteries from OZR. Inhibition of COX-1 increased basal tension in OZR and this contraction was blunted by TP receptor blockade. The vasoconstrictor responses to noradrenaline were augmented by indomethacin and by COX-2 inhibition in LZR but not in OZR. Immunohistochemical staining showed that both COX-1 and COX-2 are expressed in the endothelium of penile arteries from both LZR and OZR. Conclusions and implications: Vasoactive prostanoids were formed via constitutively active COX-1 and COX-2 pathways in normal rat penile arteries. Under conditions of insulin resistance, the release and/or effects of vasodilator prostanoids were impaired, contributing to the blunted endothelium-dependent vasodilatation and to the enhanced vasoconstriction. PMID:20082610

  4. Role of Neural NO Synthase (nNOS) Uncoupling in the Dysfunctional Nitrergic Vasorelaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

    PubMed Central

    Sánchez, Ana; Contreras, Cristina; Martínez, María Pilar; Climent, Belén; Benedito, Sara; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

    2012-01-01

    Objective Erectile dysfunction (ED) is considered as an early sign of vascular disease due to its high prevalence in patients with cardiovascular risk factors. Endothelial and neural dysfunction involving nitric oxide (NO) are usually implicated in the pathophysiology of the diabetic ED, but the underlying mechanisms are unclear. The present study assessed the role of oxidative stress in the dysfunctional neural vasodilator responses of penile arteries in the obese Zucker rat (OZR), an experimental model of metabolic syndrome/prediabetes. Methods and Results Electrical field stimulation (EFS) under non-adrenergic non-cholinergic (NANC) conditions evoked relaxations that were significantly reduced in penile arteries of OZR compared with those of lean Zucker rats (LZR). Blockade of NO synthase (NOS) inhibited neural relaxations in both LZR and OZR, while saturating concentrations of the NOS substrate L-arginine reversed the inhibition and restored relaxations in OZR to levels in arteries from LZR. nNOS expression was unchanged in arteries from OZR compared to LZR and nNOS selective inhibition decreased the EFS relaxations in LZR but not in OZR, while endothelium removal did not alter these responses in either strain. Superoxide anion production and nitro-tyrosine immunostaining were elevated in the erectile tissue from OZR. Treatment with the NADPH oxidase inhibitor apocynin or acute incubation with the NOS cofactor tetrahydrobiopterin (BH4) restored neural relaxations in OZR to levels in control arteries, while inhibition of the enzyme of BH4 synthesis GTP-cyclohydrolase (GCH) reduced neural relaxations in arteries from LZR but not OZR. The NO donor SNAP induced decreases in intracellular calcium that were impaired in arteries from OZR compared to controls. Conclusions The present study demonstrates nitrergic dysfunction and impaired neural NO signalling due to oxidative stress and nNOS uncoupling in penile arteries under conditions of insulin resistance. This

  5. High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT2R-MasR axis in obese Zucker rats

    PubMed Central

    Samuel, Preethi; Ali, Quaisar; Sabuhi, Rifat; Wu, Yonnie

    2012-01-01

    High sodium intake is known to regulate the renal renin-angiotensin system (RAS) and is a risk factor for the pathogenesis of obesity-related hypertension. The complex nature of the RAS reveals that its various components may have opposing effects on natriuresis and blood pressure regulation. We hypothesized that high sodium intake differentially regulates and shifts a balance between opposing components of the renal RAS, namely, angiotensin-converting enzyme (ACE)-ANG II-type 1 ANG II receptor (AT1R) vs. AT2-ACE2-angiotensinogen (Ang) (1–7)-Mas receptor (MasR), in obesity. In the present study, we evaluated protein and/or mRNA expression of angiotensinogen, renin, AT1A/BR, ACE, AT2R, ACE2, and MasR in the kidney cortex following 2 wk of a 8% high-sodium (HS) diet in lean and obese Zucker rats. The expression data showed that the relative expression pattern of ACE and AT1BR increased, renin decreased, and ACE2, AT2R, and MasR remained unaltered in HS-fed lean rats. On the other hand, HS intake in obese rats caused an increase in the cortical expression of ACE, a decrease in ACE2, AT2R, and MasR, and no changes in renin and AT1R. The cortical levels of ANG II increased by threefold in obese rats on HS compared with obese rats on normal salt (NS), which was not different than in lean rats. The HS intake elevated mean arterial pressure in obese rats (27 mmHg) more than in lean rats (16 mmHg). This study suggests that HS intake causes a pronounced increase in ANG II levels and a reduction in the expression of the ACE2-AT2R-MasR axis in the kidney cortex of obese rats. We conclude that such changes may lead to the potentially unopposed function of AT1R, with its various cellular and physiological roles, including the contribution to the pathogenesis of obesity-related hypertension. PMID:22592638

  6. High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT(2)R-MasR axis in obese Zucker rats.

    PubMed

    Samuel, Preethi; Ali, Quaisar; Sabuhi, Rifat; Wu, Yonnie; Hussain, Tahir

    2012-08-01

    High sodium intake is known to regulate the renal renin-angiotensin system (RAS) and is a risk factor for the pathogenesis of obesity-related hypertension. The complex nature of the RAS reveals that its various components may have opposing effects on natriuresis and blood pressure regulation. We hypothesized that high sodium intake differentially regulates and shifts a balance between opposing components of the renal RAS, namely, angiotensin-converting enzyme (ACE)-ANG II-type 1 ANG II receptor (AT(1)R) vs. AT(2)-ACE2-angiotensinogen (Ang) (1-7)-Mas receptor (MasR), in obesity. In the present study, we evaluated protein and/or mRNA expression of angiotensinogen, renin, AT(1A/B)R, ACE, AT(2)R, ACE2, and MasR in the kidney cortex following 2 wk of a 8% high-sodium (HS) diet in lean and obese Zucker rats. The expression data showed that the relative expression pattern of ACE and AT(1B)R increased, renin decreased, and ACE2, AT(2)R, and MasR remained unaltered in HS-fed lean rats. On the other hand, HS intake in obese rats caused an increase in the cortical expression of ACE, a decrease in ACE2, AT(2)R, and MasR, and no changes in renin and AT(1)R. The cortical levels of ANG II increased by threefold in obese rats on HS compared with obese rats on normal salt (NS), which was not different than in lean rats. The HS intake elevated mean arterial pressure in obese rats (27 mmHg) more than in lean rats (16 mmHg). This study suggests that HS intake causes a pronounced increase in ANG II levels and a reduction in the expression of the ACE2-AT(2)R-MasR axis in the kidney cortex of obese rats. We conclude that such changes may lead to the potentially unopposed function of AT(1)R, with its various cellular and physiological roles, including the contribution to the pathogenesis of obesity-related hypertension.

  7. Genetic obestiy: estrogenic influences on the body weight and food intake of lean and obese adult Zucker (fa/fa) rats.

    PubMed

    Gale, S K; Van Itallie, T B

    1979-07-01

    The effects of chronic estrogen withdrawal and subsequent hormone replacement on the feeding and body weight of adult lean and genetically obese Zucker rats were investigated. Following confirmation of a delay in the vaginal canalization of the fatty rat, subgroups of each genotype received either ovariectomy or sham surgery (Experiment 1). One hundred days later all subjects were injected subcutaneously (SC) with 1.0 microgram of estradiol benzoate (EB) daily for 16 treatment days (Experiment 2A). A second series of daily 2.0 microgram EB injections was administered intraperitoneally (IP) for 1 week (Experiment 2B). The first experiment revealed that ovariectomy produced overeating and similar weight gains in both genotypes. In the second experiment, SC hormone treatment completely reversed ovarian obesity in lean animals but failed to alter the food intake or weight gain of fatty rats. IP administration of EB depressed the feeding of fatty and lean animals to a comparable degree but a reduction in weight gain was observed only in the lean rats. These findings are discussed in light of current theories of estrogenic modulation of energy balance.

  8. The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats.

    PubMed

    de Nigris, Filomena; Balestrieri, Maria Luisa; Williams-Ignarro, Sharon; D'Armiento, Francesco P; Fiorito, Carmela; Ignarro, Louis J; Napoli, Claudio

    2007-08-01

    Metabolic syndrome includes most widely distributed clinical conditions such as obesity, hypertension, dislipidemia, and diabetes. Pomegranate fruit extract (PFE), rich in polyphenolic antioxidants, reduces the expression of oxidation-sensitive genes at the sites of perturbed shear-stress. The aim of this study was to evaluate the effect of PFE in comparison to regular pomegranate juice (PJ) and seed oil on the biological actions of nitric oxide (NO) and the arterial function in obese Zucker rats, a model of metabolic syndrome. Our results indicated that supplementation with PFE or PJ significantly decreased the expression of vascular inflammation markers, thrombospondin (TSP), and cytokine TGFbeta1 (P<0.05), whereas seed oil supplementation had a significant effect only on TSP-1 expression (P <0.05). Plasma nitrate and nitrite (NO(x)) levels were significantly increased by PFE and PJ (P<0.05). Furthermore, the effect of PFE in increasing endothelial NO synthase (eNOS) expression was comparable to that of PJ. These data highlight possible clinical applications of PFE in metabolic syndrome.

  9. Consumption of polyphenol-rich peach and plum juice prevents risk factors for obesity-related metabolic disorders and cardiovascular disease in Zucker rats.

    PubMed

    Noratto, Giuliana; Martino, Hercia S D; Simbo, Sunday; Byrne, David; Mertens-Talcott, Susanne U

    2015-06-01

    Polyphenols from fruits have been implied in the prevention of risk factors for cardiometabolic disorders and cardiovascular disease. The purpose of this study was to investigate if the consumption of peach and plum juice has a protective effect against obesity and metabolic disorders that promote the development of cardiovascular diseases. Obese Zucker and lean rats were fed with peach, plum juice ad libitum or placebo. Body weight gain, biochemical markers and molecular markers for inflammation and cardiovascular disease in heart tissue were quantified. Results show that peach and plum juice consumption protected against a combination of obesity-induced metabolic disorders including hyperglycemia, insulin and leptin resistance, dyslipidemia and low-density lipoprotein oxidation. This was accompanied by a decreased expression of pro-atherogenic and pro-inflammatory biomarkers in plasma and heart tissues including intercellular cell adhesion molecule-1, monocyte chemotactic protein-1, NF-κB and foam cell adherence to aortic arches. In addition, peach and plum juice consumption decreased the levels of angiotensin II in plasma and its receptor Agtr1 in heart tissues, suggesting a role of peach and plum polyphenols as peroxisome proliferator-activated receptor-γ agonists. Furthermore, only plum juice significantly prevented body weight gain and increased the ratio high-density lipoprotein cholesterol/total cholesterol in plasma. This effect is most likely attributed to the plum's higher content of polyphenols (three times that of peach). Altogether, these results imply that cardioprotective effects can be achieved by replacing drinks high in sugar content with fruit juice rich in polyphenols in a diet.

  10. Effects of dietary CLA on n-3 HUFA score and N-acylethanolamides biosynthesis in the liver of obese Zucker rats.

    PubMed

    Piras, Antonio; Carta, Gianfranca; Murru, Elisabetta; Lopes, Paula A; Martins, Susana V; Prates, José A M; Banni, Sebastiano

    2015-07-01

    We have recently shown that PPAR alpha agonists induce N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA) biosynthesis. Conjugated linoleic acid (CLA), a known dietary PPAR alpha inducer, may therefore increase OEA and PEA levels and favor docosahexaenoic acid (DHA) biosynthesis by enhancing peroxisomal β-oxidation via induction of liver PPARα. To evaluate whether CLA is able to increase DHA, OEA and PEA levels and thereby influencing liver lipid deposition in a model of visceral obesity-induced fatty liver, Zucker rats were fed a background diet rich in saturated fat with or without 1% of CLA for 4 weeks. Our data showed that CLA intake increased DHA, OEA and PEA levels in the liver by 24%, 31% and 36% respectively, and reduced hepatic lipid accumulation by 16%. We may conclude that dietary CLA is able to influence not only fatty acid metabolism but also the biosynthesis of bioactive mediators such as OEA and PEA which may contribute to ameliorate fatty liver.

  11. Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats.

    PubMed

    Batetta, Barbara; Griinari, Mikko; Carta, Gianfranca; Murru, Elisabetta; Ligresti, Alessia; Cordeddu, Lina; Giordano, Elena; Sanna, Francesca; Bisogno, Tiziana; Uda, Sabrina; Collu, Maria; Bruheim, Inge; Di Marzo, Vincenzo; Banni, Sebastiano

    2009-08-01

    Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these beneficial effects are not fully understood. In this study, we compared the effects of dietary (n-3) LCPUFA, in the form of either fish oil (FO) or krill oil (KO) balanced for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, with a control (C) diet containing no EPA and DHA and similar contents of oleic, linoleic, and alpha-linolenic acids, on ectopic fat and inflammation in Zucker rats, a model of obesity and related metabolic dysfunction. Diets were fed for 4 wk. Given the emerging evidence for an association between elevated endocannabinoid concentrations and metabolic syndrome, we also measured tissue endocannabinoid concentrations. In (n-3) LCPUFA-supplemented rats, liver triglycerides and the peritoneal macrophage response to an inflammatory stimulus were significantly lower than in rats fed the control diet, and heart triglycerides were lower, but only in KO-fed rats. These effects were associated with a lower concentration of the endocannabinoids, anandamide and 2-arachidonoylglycerol, in the visceral adipose tissue and of anandamide in the liver and heart, which, in turn, was associated with lower levels of arachidonic acid in membrane phospholipids, but not with higher activity of endocannabinoid-degrading enzymes. Our data suggest that the beneficial effects of a diet enriched with (n-3) LCPUFA are the result of changes in membrane fatty acid composition. The reduction of substrates for inflammatory molecules and endocannabinoids may account for the dampened inflammatory response and the physiological reequilibration of body fat deposition in obese rats.

  12. 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

  13. Electrospray Quadrupole Travelling Wave Ion Mobility Time-of-Flight Mass Spectrometry for the Detection of Plasma Metabolome Changes Caused by Xanthohumol in Obese Zucker (fa/fa) Rats

    PubMed Central

    Wickramasekara, Samanthi I.; Zandkarimi, Fereshteh; Morré, Jeff; Kirkwood, Jay; Legette, LeeCole; Jiang, Yuan; Gombart, Adrian F.; Stevens, Jan F.; Maier, Claudia S.

    2013-01-01

    This study reports on the use of traveling wave ion mobility quadrupole time-of-flight (ToF) mass spectrometry for plasma metabolomics. Plasma metabolite profiles of obese Zucker fa/fa rats were obtained after the administration of different oral doses of Xanthohumol; a hop-derived dietary supplement. Liquid chromatography coupled data independent tandem mass spectrometry (LC-MSE) and LC-ion mobility spectrometry (IMS)-MSE acquisitions were conducted in both positive and negative modes using a Synapt G2 High Definition Mass Spectrometry (HDMS) instrument. This method provides identification of metabolite classes in rat plasma using parallel alternating low energy and high energy collision spectral acquisition modes. Data sets were analyzed using pattern recognition methods. Statistically significant (p < 0.05 and fold change (FC) threshold > 1.5) features were selected to identify the up-/down-regulated metabolite classes. Ion mobility data visualized using drift scope software provided a graphical read-out of differences in metabolite classes. PMID:24958146

  14. 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 Central

    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-Leprfa/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-Leprfa/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-Leprfa/fa rats that received probiotics than in rats fed the placebo. Zucker-Leprfa/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-Leprfa/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-Leprfa/fa rats that received B. breve, L. rhamnosus, or the mixture, whereas L. paracasei feeding decreased IL-6 levels in the serum of Zucker-Leprfa/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. PMID:24852284

  15. Extrapancreatic effects of incretin hormones: evidence for weight-independent changes in morphological aspects and oxidative status in insulin-sensitive organs of the obese nondiabetic Zucker rat (ZFR).

    PubMed

    Colin, Ides M; Colin, Henri; Dufour, Ines; Gielen, Charles-Edouard; Many, Marie-Christine; Saey, Jean; Knoops, Bernard; Gérard, Anne-Catherine

    2016-08-01

    Incretin-based therapies are widely used to treat type 2 diabetes. Although hypoglycemic actions of incretins are mostly due to their insulinotropic/glucagonostatic effects, they may also influence extrapancreatic metabolism. We administered exendin-4 (Ex-4), a long-acting glucagon-like peptide receptor agonist, at low dose (0.1 nmol/kg/day) for a short period (10 days), in obese nondiabetic fa/fa Zucker rats (ZFRs). Ex-4-treated ZFRs were compared to vehicle (saline)-treated ZFRs and vehicle- and Ex-4-treated lean rats (LRs). Blood glucose levels were measured at days 0, 9, and 10. Ingested food and animal weight were recorded daily. On the day of sacrifice (d10), blood was sampled along with liver, epididymal, subcutaneous, brown adipose, and skeletal muscle tissues from animals fasted for 24 h. Plasma insulin and blood glucose levels, food intake, and body and epididymal fat weight were unchanged, but gross morphological changes were observed in insulin-sensitive tissues. The average size of hepatocytes was significantly lower in Ex-4-treated ZFRs, associated with decreased number and size of lipid droplets and 4-hydroxy-2-nonenal (HNE) staining, a marker of oxidative stress (OS). Myocytes, which were smaller in ZFRs than in LRs, were significantly enlarged and depleted of lipid droplets in Ex-4-treated ZFRs. Weak HNE staining was increased by Ex-4. A similar observation was made in brown adipose tissue, whereas the elevated HNE staining observed in epididymal adipocytes of ZFRs, suggestive of strong OS, was decreased by Ex-4. These results suggest that incretins by acting on OS in insulin-sensitive tissues may contribute to weight-independent improvement in insulin sensitivity.

  16. Effects of Repeated Acute Stress in Obese and Non-Obese Rats

    DTIC Science & Technology

    2008-04-02

    stocks unhealthy snack foods and does not offer fresh fruit and vegetables . During periods of stress, limited access to unhealthy food types - a form of...one obese offspring was about 25% (Zucker & Zucker, 1961). The fatty Zuckers are pigmented typically with a black or brown and white coat. The obese...sucrose-flavored solutions (Sell et aI., 2002) or vegetable shortening (Harris et aI., 1998). Rats fed a high-fat diet, which consists of 20% vegetable

  17. Alpha-lipoic acid supplementation reduces mTORC1 signaling in skeletal muscle from high fat fed, obese Zucker rats.

    PubMed

    Li, Zhuyun; Dungan, Cory M; Carrier, Bradley; Rideout, Todd C; Williamson, David L

    2014-12-01

    The mammalian target of rapamycin (mTOR) signaling pathway is hyperactive in liver, adipose and skeletal muscle tissues of obese rodents. Alpha-lipoic acid (αLA) has been well accepted as a weight-loss treatment, though there are limited studies on its effect on mTOR signaling in high-fat fed, obese rodents. Therefore, the goal of this study was to determine mTOR signaling and oxidative protein alterations in skeletal muscle of high-fat fed, obese rats after αLA supplementation. Phosphorylation of the mTOR substrate, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and eIF4B were significantly reduced (p < 0.05) in muscle from αLA supplemented rats. Activation of AMP-activated protein kinase (AMPK), an mTOR inhibitory kinase, was higher (p < 0.05) in the αLA group. Protein expression of markers of oxidative metabolism, acetyl CoA carboxylase (ACC), cytochrome c oxidase IV (COX IV), peroxisome proliferator-activated receptor (PPAR), and PPAR gamma coactivator 1-alpha (PGC-1α) were significantly higher (p < 0.05) after αLA supplementation compared to non-supplemented group. Our findings show that αLA supplementation limits the negative ramifications of consuming a high fat diet on skeletal muscle markers of oxidative metabolism and mTORC1 signaling.

  18. Effect of three anorectic drugs on central catecholamine levels and synthesis in the Zucker rat.

    PubMed

    Orosco, M; Bremond, J; Jacquot, C; Cohen, Y

    1983-01-01

    1. Genetically obese Zucker rats and their lean littermates were treated during 5 days with fenfluramine, mazindol or amphetamine. Norepinephrine and dopamine levels were assayed in the hypothalamus, striatum, medulla-oblongata pons and remainder of the brain, and the amine synthesis was estimated, when possible. 2. Fenfluramine acted especially on norepinephrine in the obese rat hypothalamus. 3. Mazindol was active on norepinephrine and dopamine levels only in obese animals. 4. Amphetamine acted on norepinephrine levels only in obese rats and on dopamine levels in both obese and lean rats.

  19. Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

    SciTech Connect

    Finan, A.; Cleary, M.P.

    1986-03-05

    DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either (1-/sup 14/C) glucose or (6-/sup 14/C) glucose resulted in significant decreases in CO/sub 2/ production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats.

  20. Effect of three anorectic drugs on brain GABA levels and synthesis in the Zucker rat.

    PubMed

    Orosco, M; Bremond, J; Jacquot, C; Cohen, Y

    1983-01-01

    1. Genetically obese Zucker rats and their lean littermates were submitted to a subchronic treatment with fenfluramine, mazindol and amphetamine. GABA levels and synthesis index were measured in different brain areas. 2. GABA levels, similar in obese and lean controls, were not changed after the three treatments. 3. A higher synthesis index of GABA was found in lean rats, in the striatum after mazindol and in the hypothalamus after amphetamine. 4. The three drugs increased the synthesis index of GABA in the remainder of the brain of both obese and lean rats.

  1. Kynurenic acid, an aryl hydrocarbon receptor ligand, is elevated in serum of Zucker fatty rats

    PubMed Central

    Oxenkrug, G; Cornicelli, J; van der Hart, M; Roeser, J; Summergrad, P

    2016-01-01

    Obesity is an increasingly urgent global problem and the molecular mechanisms of obesity are not fully understood. Dysregulation of the tryptophan (Trp) – kynurenine (Kyn) metabolic pathway (TKP) have been suggested as a mechanism of obesity and described in obese humans and in animal models of obesity. However, to the best of our knowledge, TKP metabolism has not been studied in leptin-receptor-deficient Zucker fatty rats (ZFR) (fa/fa), the best-known and most widely used rat model of obesity. We were interested to determine if there are any deviations of TKP in ZFR. Concentrations of major TKP metabolites were evaluated (HPLC- MS method) in serum of ZFR (fa/fa) and age-matched lean rats (FA/-). Concentrations of kynurenic acid (KYNA) were 50% higher in ZFR than in lean rats (p<0.004, Mann-Whitney two-tailed test). Anthranilic acid (AA) concentrations, while elevated by 33%, did not reach statistical significance (p<0.04, one-tailed test). Elevated KYNA serum concentrations might contribute to development of obesity via KYNA-induced activation of aryl hydrocarbon receptor. Present results warrant further studies of KYNA and AA in ZFR and other animal models of obesity. PMID:27738521

  2. 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 occurs over time when you eat more calories ...

  3. Sulfur amino acid metabolism in Zucker diabetic fatty rats.

    PubMed

    Kwak, Hui Chan; Kim, Young-Mi; Oh, Soo Jin; Kim, Sang Kyum

    2015-08-01

    The present study was aimed to investigate the metabolomics of sulfur amino acids in Zucker diabetic fatty (ZDF) rats, an obese type 2 diabetic animal model. Plasma levels of total cysteine, homocysteine and methionine, but not glutathione (GSH) were markedly decreased in ZDF rats. Hepatic methionine, homocysteine, cysteine, betaine, taurine, spermidine and spermine were also decreased. There are no significant difference in hepatic S-adenosylmethionine, S-adenosylhomocysteine, GSH, GSH disulfide, hypotaurine and putrescine between control and ZDF rats. Hepatic SAH hydrolase, betaine-homocysteine methyltransferase and methylene tetrahydrofolate reductase were up-regulated while activities of gamma-glutamylcysteine ligase and methionine synthase were decreased. The area under the curve (AUC) of methionine and methionine-d4 was not significantly different in control and ZDF rats treated with a mixture of methionine (60mg/kg) and methionine-d4 (20mg/kg). Moreover, the AUC of the increase in plasma total homocysteine was comparable between two groups, although the homocysteine concentration curve was shifted leftward in ZDF rats, suggesting that the plasma total homocysteine after the methionine loading was rapidly increased and normalized in ZDF rats. These results show that the AUC of plasma homocysteine is not responsive to the up-regulation of hepatic BHMT in ZDF rats. The present study suggests that the decrease in hepatic methionine may be responsible for the decreases in its metabolites, such as homocysteine, cysteine, and taurine in liver and consequently decreased plasma homocysteine levels.

  4. Acute and chronic administration of immunomodulators induces anorexia in Zucker rats.

    PubMed

    Lugarini, F; Hrupka, B J; Schwartz, G J; Plata-Salaman, C R; Langhans, W

    2005-01-31

    To investigate the possible involvement of leptin signaling in lipopolysaccharide (LPS) anorexia, we compared the anorectic effect of LPS in genetically obese (fa/fa) Zucker rats and in their lean (Fa/?) counterparts. The effects of interleukin-1beta (IL-1beta) and muramyl dipeptide (MDP) were also tested. LPS [100 microg/kg body weight (BW)], IL-1beta (2 microg/kg BW) and MDP (2.2 mg/kg BW) injected intraperitoneally (i.p.) at lights out reduced food intake similarly in obese and lean rats. LPS injection at 500 or 1000 microg/kg BW (i.p.) also reduced food intake and BW similarly in obese and lean rats, but obese regained BW faster than lean rats. LPS (2.45 microg or 9.8 microg/h/rat) administered chronically with i.p. implanted osmotic pumps reduced food intake similarly on experimental day 1, regardless of the genotype. After day 3, the lean rats' anorectic response and recovery were dose-dependent, whereas the anorectic response in obese rats was minimally affected by dose (significant dose effect only on day 3). Again, obese rats regained lost BW faster than lean rats. These results do not support a role for leptin as the sole mediator of anorexia induced by bacterial products (LPS and MDP) and IL-1beta.

  5. Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats

    PubMed Central

    2010-01-01

    Background Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. Methods In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7). Results Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. Conclusions Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats. PMID:20576113

  6. Obesity

    MedlinePlus

    ... In some cases, weight-loss surgery, also called bariatric surgery, is an option. Weight-loss surgery limits the ... et al. Treatment of obesity: The impact of bariatric surgery. In: Current Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy. 2nd ...

  7. Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats.

    PubMed

    Agil, Ahmad; Rosado, Isaac; Ruiz, Rosario; Figueroa, Adriana; Zen, Nourahouda; Fernández-Vázquez, Gumersindo

    2012-03-01

    The aim of this study was to investigate the effects of melatonin on glucose homeostasis in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups, each composed of ten rats: naive (N), vehicle treated (V), and melatonin treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. ZDF rats developed DM (fasting hyperglycemia, 460±39.8mg/dL; HbA(1) c 8.3±0.5%) with both insulin resistance (HOMA-IR 9.28±0.9 versus 1.2±0.1 in ZL) and decreased β-cell function (HOMA1-%B) by 75%, compared with ZL rats. Melatonin reduced fasting hyperglycemia by 18.6% (P<0.05) and HbA(1) c by 11% (P<0.05) in ZDF rats. Also, melatonin lowered insulinemia by 15.9% (P<0.05) and HOMA-IR by 31% (P<0.01) and increased HOMA1-%B by 14.4% (P<0.05). In addition, melatonin decreased hyperleptinemia by 34% (P<0.001) and raised hypoadiponectinemia by 40% (P<0.001) in ZDF rats. Moreover, melatonin reduced serum free fatty acid levels by 13.5% (P<0.05). These data demonstrate that oral melatonin administration ameliorates glucose homeostasis in young ZDF rats by improving both insulin action and β-cell function. These observations have implications on melatonin's possible use as a new pharmacologic therapy for improving glucose homeostasis and of obesity-related T2DM, in young subjects.

  8. Obesity

    MedlinePlus

    ... little free time may have less time to exercise. The term eating disorder means a group of medical conditions that have an unhealthy focus on eating, dieting, losing or gaining weight, and body image. A person may be obese, follow an unhealthy ...

  9. Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats.

    PubMed

    Wergedahl, Hege; Liaset, Bjørn; Gudbrandsen, Oddrun Anita; Lied, Einar; Espe, Marit; Muna, Ziad; Mørk, Sverre; Berge, Rolf K

    2004-06-01

    There is growing evidence that soy protein improves the blood lipid profiles of animals and humans. We compared the effects of fish protein hydrolysate (FPH), soy protein, and casein (control) on lipid metabolism in Wistar rats and genetically obese Zucker (fa/fa) rats. In Zucker rats, FPH treatment affected the fatty acid composition in liver, plasma, and triacylglycerol-rich lipoproteins. The mRNA levels of Delta 5 and Delta 6 desaturases were reduced by FPH and soy protein feeding compared with casein feeding. In Zucker rats both FPH and soy protein treatment reduced the plasma cholesterol level. Furthermore, the HDL cholesterol:total cholesterol ratio was greater in these rats and in the Wistar rats fed FPH and soy protein compared with those fed casein. Although fecal total bile acids were greater in soy protein-fed Zucker rats than in casein-fed controls, those fed FPH did not differ from the controls. However, the acyl-CoA:cholesterol acyltransferase activity was reduced in Zucker rats fed FPH and tended to be lower (P = 0.13) in those fed soy protein compared with those fed casein. Low ratios of methionine to glycine and lysine to arginine in the FPH and soy protein diets, compared with the casein diet, may be involved in lowering the plasma cholesterol concentration. Our results indicate that the effects of FPH and soy protein on fatty acid metabolism are similar in many respects, but the hypocholesterolemic effects of FPH and soy protein appear to be due to different mechanisms. FPH may have a role as a cardioprotective nutrient.

  10. 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.

  11. Obesity Preserves Myocardial Function During Blockade of the Glycolytic Pathway

    PubMed Central

    de Campos, Dijon Henrique Salomé; Leopoldo, André Soares; Lima-Leopoldo, Ana Paula; do Nascimento, André Ferreira; de Oliveira-Junior, Silvio Assis; da Silva, Danielle Cristina Tomaz; Sugizaki, Mario Mateus; Padovani, Carlos Roberto; Cicogna, Antonio Carlos

    2014-01-01

    Background Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished. Objective Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity. Methods 30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV). Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway. Results Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C. Conclusion The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle. PMID:25352507

  12. Pressor recovery after acute stress is impaired in high fructose-fed Lean Zucker rats.

    PubMed

    Thompson, Jennifer A; D'Angelo, Gerard; Mintz, James D; Fulton, David J; Stepp, David W

    2016-06-01

    Insulin resistance is a powerful predictor of cardiovascular disease; however, the mechanistic link remains unclear. This study aims to determine if early cardiovascular changes associated with short-term fructose feeding in the absence of obesity manifest as abnormal blood pressure control. Metabolic dysfunction was induced in Lean Zucker rats by short-term high-fructose feeding. Rats were implanted with telemetry devices for the measurement of mean arterial blood pressure (MAP) and subjected to air jet stress at 5 and 8 weeks after feeding. Additional animals were catheterized under anesthesia for the determination of MAP and blood flow responses in the hind limb and mesenteric vascular beds to intravenous injection of isoproterenol (0.001-0.5 μm), a β-adrenergic agonist. Metabolic dysfunction in high-fructose rats was not accompanied by changes in 24-h MAP Yet, animals fed a high-fructose diet for 8 weeks exhibited a marked impairment in blood pressure recovery after air-jet stress. Dose-dependent decreases in MAP and peripheral blood flow in response to isoproterenol treatment were significantly attenuated in high-fructose rats. These data suggest that impaired blood pressure recovery to acute mental stress precedes the onset of hypertension in the early stages of insulin resistance. Further, blunted responses to isoproterenol implicate β2-adrenergic sensitivity as a possible mechanism responsible for altered blood pressure control after short-term high-fructose feeding.

  13. 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

  14. Breast Cancer and Early Onset Childhood Obesity: Cell Specific Gene Expression in Mammary Epithelia and Adipocytes

    DTIC Science & Technology

    2007-07-01

    hormone leptin (ob/ob mice) or its receptor (db/db mice, Zucker rat). These leptin signaling impaired animals are resistant to oncogene and...chemically induced mammary tumors (3,4). However, human obesity is not generally caused by mutations in leptin or its receptor (5). As expression of leptin ...morbidity factors associated with human obesity in the three groups of rats, including Leptin , Free fatty acids (FFA), triglycerides (TG) and insulin

  15. Deciphering bacterial community changes in zucker diabetic fatty rats based on 16S rRNA gene sequences analysis

    PubMed Central

    Xiang, Hong; Li, Shu; Liang, Lina; Sui, Hua; Zhan, Libin; Lu, Xiaoguang

    2016-01-01

    The aim of the present pilot study was deciphering bacterial community changes in Zucker diabetic fatty rats (ZDF rats), a model of type 2 diabetes. Recent studies unmasked that the status of gastrointestinal tract microbiota has a marked impact on nutrition-related syndromes such as obesity and type-2 diabetes (T2D). In this study, samples taken from the gastrointestinal tracts (GI tracts) of ZDF and their lean littermates (ZL rats) were subjected to 16S rRNA gene sequence-based analysis to examine the characteristic bacterial communities, including those located in the stomach, duodenum, jejunum, ileum, cecum and feces. Results revealed that the Firmicutes/Bacteroidetes ratio was increased and greater numbers of Lactobacillus were detected along GI tracts in ZDF rats compared to ZL rats. In conclusion, this work is the first study to systematically characterize bacterial communities along ZDF rat GI tract and provides substantial evidence supporting a prospective strategy to alter the GI microbial communities improving obesity and T2D. PMID:27418144

  16. Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats

    PubMed Central

    Chen, Wen-Pei; Wang, Yan-Dong; Ma, Yan; Zhang, Zi-Yang; Hu, Lu-Yun; Lin, Jun-Li; Lin, Bao-Qin

    2015-01-01

    AIM To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type-2 diabetes, and then to investigate the mechanisms. METHODS ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism. PMID:26682154

  17. Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase.

    PubMed

    Winiarska, Katarzyna; Dzik, Jolanta M; Labudda, Mateusz; Focht, Dorota; Sierakowski, Bartosz; Owczarek, Aleksandra; Komorowski, Lukasz; Bielecki, Wojciech

    2016-01-01

    Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47(phox) subunits, elevated level of p47(phox) phosphorylation, and enlarged phospho-p47(phox) and p67(phox) content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho-p47(phox) and p67(phox) . Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.

  18. Lipotoxic heart disease in obese rats: Implications for human obesity

    PubMed Central

    Zhou, Yan-Ting; Grayburn, Paul; Karim, Asad; Shimabukuro, Michio; Higa, Moritake; Baetens, Dany; Orci, Lelio; Unger, Roger H.

    2000-01-01

    To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of ceramide, a mediator of apoptosis, were 2–3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids. PMID:10677535

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

    SciTech Connect

    Hsun-Wei Huang, Tom; Peng Gang; Qian Li, George; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2006-02-01

    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 had 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.

  20. Basal insulin hypersecretion in insulin-resistant Zucker diabetic and Zucker fatty rats: role of enhanced fuel metabolism.

    PubMed

    Zhou, Y P; Cockburn, B N; Pugh, W; Polonsky, K S

    1999-07-01

    The biochemical mechanisms responsible for basal hyperinsulinemia in insulin-resistant states have not been fully defined. We therefore studied pancreatic beta-cell function in vitro to characterize the relative importance of fuel metabolism or secretion via a constitutive pathway in the maintenance of high basal insulin secretion in Zucker diabetic fatty (ZDF) and Zucker fatty (ZF) rats. Insulin secretion from ZF (10+/-1.8 v 5+/-0.6 pmol/ng DNA/h) and ZDF (30+/-4 v 7+/-0.8 pmol/ng DNA/h) islets at 2.8 mmol/L glucose was two to four times greater than secretion from islets of lean littermate control rats. In response to a decreasing glucose concentration (from 12 to 0 mmol/L), a paradoxical increase in insulin secretion was observed in perfused ZDF rat pancreas. Insulin secretion at 2.8 mmol/L glucose was suppressed approximately 70% to 80% in islets from ZDF and ZF rats following exposure to diazoxide, a K+-adenosine triphosphate (K(ATP)) channel opener that inhibits membrane depolarization, or rotenone and oligomycin, agents that inhibit ATP production, or by incubation at 23 degrees C. Inhibition of glycolysis with mannoheptulose, 2-deoxyglucose, and iodoacetate or fatty acid oxidation with a carnitine palmitoyltransferase I inhibitor also significantly inhibited basal insulin secretion in islets of ZDF and ZF rats but not their lean littermates. Furthermore, the glycolytic flux at 2.8 mmol/L glucose was significantly higher in ZDF islets versus ZDF lean littermate (ZLC) islets (2.2+/-0.1 v 3.7+/-0.3 pmol/ng DNA/2 h, P < .01) and was suppressed by mannoheptulose. In ZDF and ZF islets, high basal insulin secretion was maintained despite a 50% reduction in the rate of proinsulin/insulin biosynthesis at 2.8 mmol/L glucose. The rate of proinsulin to insulin conversion and the ratio of proinsulin to insulin secretion by islets of ZDF rats were similar to the values in the lean littermates. Thus, basal hypersecretion in these two insulin-resistant models appears to be

  1. C-Peptide-Based Assessment of Insulin Secretion in the Zucker Fatty Rat: A Modelistic Study

    PubMed Central

    Di Nardo, Francesco; Cogo, Carla E.; Faelli, Emanuela; Morettini, Micaela; Burattini, Laura; Ruggeri, Piero

    2015-01-01

    A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT) was performed in seven Zucker fatty rats (ZFR), 7-to-9week-old, and seven age-matched Zucker lean rats (ZLR). The minimal model of C-peptide (CPMM), originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM). Our results showed that the present CPMM-based interpretation of data is able to: 1) provide a suitable fit of C-Peptide data; 2) achieve a satisfactory estimation of parameters of interest 3) quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t), and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of β-cell responsiveness to glucose stimulus (first-phase, Ф1, second-phase, Ф2, and steady-state, Фss, never assessed in Zucker rats before; 4) detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess β-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation. PMID:25938808

  2. Melatonin treatment protects liver of Zucker rats after ischemia/reperfusion by diminishing oxidative stress and apoptosis.

    PubMed

    Kireev, Roman; Bitoun, Samuel; Cuesta, Sara; Tejerina, Alejandro; Ibarrola, Carolina; Moreno, Enrique; Vara, Elena; Tresguerres, Jesus A F

    2013-02-15

    Fatty livers occur in up to 20% of potential liver donors and increase cellular injury during the ischemia/reperfusion phase, so any intervention that could enable a better outcome of grafts for liver transplantation would be very useful. The effect of melatonin on liver ischemia/reperfusion injury in a rat model of obesity and hepatic steatosis has been investigated. Forty fa/fa Zucker rats were divided in 4 groups. 3 groups were subjected to 35 min of warm hepatic ischemia and 36 h of reperfusion. One experimental group remained untreated and 2 were given 10mg/kg melatonin intraperitoneally or orally. Another group was sham-operated. Plasma ALT, AST and hepatic content of ATP, MDA, hydroxyalkenals, NOx metabolites, antioxidant enzyme activity, caspase-9 and DNA fragmentation were determined in the liver. The expression of iNOS, eNOS, Bcl2, Bax, Bad and AIF were determined by RT-PCR Melatonin was effective at decreasing liver injury by both ways as assessed by liver transaminases, markers of apoptosis, of oxidative stress and improved liver ATP content. Melatonin administration decreased the activities or levels of most of the parameters measured in a beneficial way, and our study identified also some of the mechanisms of protection. We conclude that administration of melatonin improved liver function, as well as markers of pro/antioxidant status and apoptosis following ischemia/reperfusion in obese rats with fatty liver. These data suggest that this substance could improve outcome in patients undergoing liver transplantation who receive a fatty liver implant and suggest the need of clinical trials with it in liver transplantation.

  3. 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

  4. 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

  5. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-{alpha}-mediated transcription of fatty acid metabolic genes

    SciTech Connect

    Huang, Tom H.-W.; Yang Qinglin; Harada, Masaki; Uberai, Jasna; Radford, Jane; Li, George Q.; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2006-01-15

    Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-{alpha} plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-{alpha} activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-{alpha} mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-{alpha}-mediated FA metabolic gene transcription.

  6. 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

  7. NADPH oxidase inhibitor, apocynin, improves renal glutathione status in Zucker diabetic fatty rats: a comparison with melatonin.

    PubMed

    Winiarska, Katarzyna; Focht, Dorota; Sierakowski, Bartosz; Lewandowski, Krystian; Orlowska, Marta; Usarek, Michal

    2014-07-25

    Apocynin (4'-hydroxy-3'-methoxyacetophenone) is the most commonly used NADPH oxidase (Nox) inhibitor. However, its application raises serious controversies, as the compound has been reported to reveal some prooxidative effects. The aim of this study was to elucidate apocynin action on glutathione, the main intracellular antioxidant, metabolism in kidneys of Zucker diabetic fatty (ZDF) rat, a well established model of diabetes type 2. Additionally, apocynin effects were compared with those of melatonin. The experiments were performed on five groups of animals: (1) untreated lean (?/+) ZDF rats, (2) ZDF ?/+ rats treated with apocynin (2 g/l) in drinking water, (3) untreated obese diabetic (fa/fa) ZDF rats, (4) ZDF fa/fa rats treated with apocynin (2 g/l) in drinking water, and (5) ZDF fa/fa rats treated with melatonin (20 mg/l) in drinking water. After 8weeks of the treatment, the following parameters were measured in kidneys: NADPH oxidase activity, the rate of hydroxyl free radicals (HFR) production, GSH and GSSG content and the activities of the enzymes of glutathione metabolism: γ-glutamylcysteine synthetase (GCS), glutathione reductase (GR) and glutathione peroxidase (GPx). Compared to ?/+ controls, ZDF fa/fa rats exhibited increased Nox activity, accelerated HFR generation and dramatically lowered GSH/GSSG ratio accompanied by increased GPx and diminished GCS activities. In case of diabetic animals, apocynin treatment resulted in attenuation of both Nox activity and HFR production, restoration of control GSH/GSSG ratio (due to both an increase in GSH and a decline in GSSG content), normalization of GPx activity and a slight increase in GCS activity. Similar observations were made upon melatonin application to ZDF fa/fa rats. Thus, it is concluded that, in the diabetic model studied, apocynin extends a beneficial effect on renal glutathione homeostasis. The mechanism of this phenomenon involves attenuation of glutathione peroxidase activity, which is

  8. Blueberry intake alters skeletal muscle and adipose tissue peroxisome proliferator-activated receptor activity and reduces insulin resistance in obese rats.

    PubMed

    Seymour, E Mitchell; Tanone, Ignasia I; Urcuyo-Llanes, Daniel E; Lewis, Sarah K; Kirakosyan, Ara; Kondoleon, Michael G; Kaufman, Peter B; Bolling, Steven F

    2011-12-01

    Metabolic syndrome can precede the development of type 2 diabetes and cardiovascular disease and includes phenotypes such as obesity, systemic inflammation, insulin resistance, and hyperlipidemia. A recent epidemiological study indicated that blueberry intake reduced cardiovascular mortality in humans, but the possible genetic mechanisms of this effect are unknown. Blueberries are a rich source of anthocyanins, and anthocyanins can alter the activity of peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism. The effect of blueberry intake was assessed in obesity-prone rats. Zucker Fatty and Zucker Lean rats were fed a higher-fat diet (45% of kcal) or a lower-fat diet (10% of kcal) containing 2% (wt/wt) freeze-dried whole highbush blueberry powder or added sugars to match macronutrient and calorie content. In Zucker Fatty rats fed a high-fat diet, the addition of blueberry reduced triglycerides, fasting insulin, homeostasis model index of insulin resistance, and glucose area under the curve. Blueberry intake also reduced abdominal fat mass, increased adipose and skeletal muscle PPAR activity, and affected PPAR transcripts involved in fat oxidation and glucose uptake/oxidation. In Zucker Fatty rats fed a low-fat diet, the addition of blueberry also significantly reduced liver weight, body weight, and total fat mass. Finally, Zucker Lean rats fed blueberry had higher body weight and reduced triglycerides, but all other measures were unaffected. In conclusion, whole blueberry intake reduced phenotypes of metabolic syndrome in obesity-prone rats and affected PPAR gene transcripts in adipose and muscle tissue involved in fat and glucose metabolism.

  9. 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.

  10. Nebivolol Attenuates Redox-Sensitive Glomerular and Tubular Mediated Proteinuria in Obese Rats

    PubMed Central

    Habibi, Javad; Hayden, Melvin R.; Sowers, James R.; Pulakat, Lakshmi; Tilmon, Roger D.; Manrique, Camila; Lastra, Guido; DeMarco, Vincent G.

    2011-01-01

    Obesity and insulin resistance-related proteinuria is associated with oxidative stress and impaired tissue bioavailable nitric oxide. Recent data suggest that nicotinamide adenine dinucleotide phosphate oxidase-mediated oxidative injury to the proximal tubule, like that seen in the glomerulus, contributes to proteinuria in insulin-resistant states. The vasodilator β-blocker nebivolol reduces nicotinamide adenine dinucleotide phosphate oxidase activity, increases bioavailable nitric oxide, and improves insulin sensitivity. To test the hypothesis that a treatment strategy that reduces oxidative stress and attenuates obesity-associated increases in glomerular and proximal tubule derived protein, we treated young Zucker obese (ZO) and age-matched Zucker lean male rats with nebivolol (10 mg · kg−1 · d−1) for 21 d. Compared with Zucker lean, ZO controls exhibited increased proteinuria and γ-glutamyl transpeptidase, reductions in systemic insulin sensitivity in association with increased renal renin, (pro)renin receptor, angiotensin II type 1 receptor, and mineralocorticoid receptor immunostaining, oxidative stress, and glomerular tubular structural abnormalities that were substantially improved with in vivo nebivolol treatment. Nebivolol treatment also led to improvements in glomerular podocyte foot-process effacement and improvement in podocyte-specific proteins (nephrin and synaptopodin) as well as proximal tubule-specific proteins (megalin and lysosomal-associated membrane protein-2) and proximal tubule ultrastructural remodeling in the ZO kidney. Our findings support the notion that obesity and insulin resistance lead to increased glomerulotubular oxidative stress and resultant glomerular and tubular sources of excess urine protein. Furthermore, the results of this study suggest the beneficial effect of nebivolol on proteinuria was derived from improvements in weight and insulin sensitivity and reductions in renal oxidative stress in a state of obesity and

  11. [The participation of opioids in the antinociceptive effect induced by the stimulation of hypothalamic "pleasure zones" in 20- to 30-day-old rabbits].

    PubMed

    Butkevich, I P; Kassil', V G

    1995-01-01

    The involvement of opioid peptides in the mediation of inhibitory influences of the positive reinforcement system ("reward areas") on the evoked potential (EPs) recorded in the thalamic parafascicular complex (CM-Pf) in response to the nociceptive electrodermal stimulation of the hind paw in 20-30 day rabbits has been studied. Electrical stimulation of "reward areas" identified in the preliminary behavioural experiments inhibited the EPs. The systemic injection of naloxone potentiated the antinociceptive effect of "reward areas" stimulation in 75% of cases under the incomplete inhibition of EPs (the decrease of EPs amplitude) but decreased its inhibitory effect in 87% of cases under the complete inhibition of EPs. Naloxone did not change the inhibitory effect of "reward areas" stimulation suggesting to the relationship of analgesic "reward areas" function with nonopioid mechanisms too. On the basis of the comparison of the present data and the ones obtained before it can be inferred that opioid mechanism in realization of antinociceptive influence of "reward areas" stimulation on EPs in CM-Pf is more important for 20-30 day rabbits compared with 41-60 day ones. The correlation of the phenomenon under investigation with the formation of neurotransmitter systems has been discussed.

  12. Dietary t10,c12-CLA but not c9,t11 CLA reduces adipocyte size in the absence of changes in the adipose renin-angiotensin system in fa/fa Zucker rats.

    PubMed

    DeClercq, Vanessa; Zahradka, Peter; Taylor, Carla G

    2010-11-01

    In obesity, increased activity of the local renin-angiotensin system (RAS) and enlarged adipocytes with altered adipokine production are linked to the development of obesity-related health problems and cardiovascular disease. Mixtures of conjugated linoleic acid (CLA) isomers have been shown to reduce adipocyte size and alter the production of adipokines. The objective of this study was to investigate the effects of feeding individual CLA isomers on adipocyte size and adipokines associated with the local adipose RAS. Male fa/fa Zucker rats received either (a) control, (b) cis(c)9,trans(t)11-CLA, or (c) t10,c12-CLA diet for 8 weeks. The t10,c12-CLA isomer reduced adipocyte size and increased cell number in epididymal adipose tissue. RT-PCR and Western blot analysis revealed that neither CLA isomer altered mRNA or protein levels of angiotensinogen or AngII receptors in adipose tissue. Likewise, levels of the pro-inflammatory cytokines TNF-α and IL-6 or the anti-inflammatory cytokine IL-10 were unchanged in adipose tissue. Similarly, neither CLA isomer had any effect on phosphorylation nor DNA binding of NF-κB. Our results suggest that although the t10,c12-CLA isomer had beneficial effects on reducing adipocyte size in obese rats, this did not translate into changes in the local adipose RAS or associated adipokines.

  13. 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…

  14. Neuropeptides and obesity.

    PubMed

    Beck, B

    2000-10-01

    This review focuses on the expression, content, and release of neuropeptides and on their role in the development of obesity in animal models with single-gene mutations. The balance between neuropeptides that contribute to the control of feeding behavior is profoundly and variously altered in these models, supporting the concept of the existence of several types of obesity. The hypothalamic neuropeptide Y (NPY) and the pro-opiomelanocortin (POMC) systems are the networks most studied in relation to energy intake. Both receive information about the nutritional status and the level of energy storage through insulin and leptin signaling mediated by specific receptors located on POMC and NPY neurons present predominantly in the arcuate nucleus (ARC). When leptin signaling is defective, through a defect in either the receptor (Zucker fa/fa rat, cp/cp rat, and db/db mouse) or in the peptide itself (ob/ob mouse), the NPY system is upregulated as shown by mRNA overexpression and increased peptide release, whereas the content and/or release of some inhibitory peptides (neurotensin, cholecystokinin) are diminished. For the POMC system, there is a complex interaction between the tonic inhibition of food intake exerted by alpha-melanocyte-stimulating hormone (alpha-MSH) and the Agouti-related protein at the level of the type 4 melanocortin receptor. The latter peptide is coexpressed with NPY in the ARC. Corticotropin-releasing factor (CRF) is the link between food intake and environmental factors. It not only inhibits food intake and prevents weight gain, likely through hypothalamic effects, but also activates the hypothalamo-pituitary axis and therefore contributes to energy storage in adipose tissue. The factors that prod the CRF system toward the hypothalamic or hypothalamo-pituitary axis system remain to be more clearly defined (comodulators, connections between limbic system and ARC, cellular location, and type of receptors, etc. ). The pathways used by all of these

  15. Renal podocyte apoptosis in Zucker diabetic fatty rats: involvement of methylglyoxal-induced oxidative DNA damage.

    PubMed

    Kim, J; Sohn, E; Kim, C-S; Kim, J S

    2011-01-01

    Methylglyoxal (MGO) is a cytotoxic metabolite produced by in-vivo glycolysis that may result in diabetic complications. The aim of this study was to determine whether MGO and oxidative stress caused apoptosis of renal podocytes in the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes mellitus. Male ZDF rats aged 21 weeks developed marked hyperglycaemia with proteinuria and albuminuria. Immunohistochemical evaluation of sections of kidney demonstrated expression of MGO and 8-hydroxydeoxyguanosine (8-OHdG) in the podocytes of both normoglycaemic and diabetic rats. Podocyte apoptosis was shown through application of the TUNEL method. These findings suggest that expression of MGO and 8-OHdG is caused by hyperglycaemia, and that this expression is associated with the observed apoptosis of podocytes and is related to diabetic nephropathy.

  16. Transcutaneous Auricular Vagus Nerve Stimulation Triggers Melatonin Secretion and Is Antidepressive in Zucker Diabetic Fatty Rats

    PubMed Central

    Rong, Peijing; McCabe, Michael F.; Zhao, Jingjun; Ben, Hui; Wang, Xing; Wang, Shuxing

    2014-01-01

    Decreased circulating melatonin is implicated in depression. We recently found that Zucker diabetic fatty rats (ZDF, fa/fa) develop depression-like behaviors and that transcutaneous auricular vagus nerve stimulation (taVNS) is antidepressive in ZDF rats. Here we studied whether the ZDF rats could be used as a depression rodent model and whether the antidepressive effect of taVNS is mediated through modulation of melatonin secretion. Adult male ZDF and Zucker lean (ZL, fa/+) littermates were used. 30 min-taVNS procedures (2/15 Hz, 2 mA) were administered once daily under anesthesia for 34 consecutive days in pineal intact ZDF (n = 8) and ZL (n = 6) rats, as well as in pinealectomized ZDF rats (n = 8). Forced swimming test (FST) was used to determine depression-like behavior and ELISA to detect plasma melatonin concentration on day 35. We found that naïve ZDF rats had a longer immobility time in FST and that long-term (34 days) taVNS treatment ameliorated the depression-like behavior. In both pineal intact and pinealectomized ZDF rats, taVNS induced acute melatonin secretion, both during and after the taVNS session. A low melatonin level is related to the poor FST performance in ZDF rats (R = −0.544) in contrast to ZL rats (R = 0.247). In conclusion, our results show that ZDF rats are ideal candidates of innate depression and that taVNS is antidepressive through triggering melatonin secretion and increasing its production. PMID:25347185

  17. Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat.

    PubMed

    Ruggeri, Piero; Brunori, Andrea; Cogo, Carla E; Storace, Daniela; Di Nardo, Francesco; Burattini, Roberto

    2006-08-01

    Somatosympathetic reflexes were studied in young hyperinsulinemic, insulin-resistant (Zucker fatty) rats (ZFR) and a related control (Zucker lean) strain (ZLR). Glucose metabolism was characterized by minimal model analysis of intravenous glucose tolerance test data. Seven-week-old ZFR (n=18) and ZLR (n=17) were studied under pentobarbital anesthesia. Mean body weight and plasma glucose and insulin concentration were significantly greater (P<0.05) in ZFR than in ZLR, whereas basal values of mean arterial pressure (MAP) and heart rate (HR) were not significantly different. Increments of MAP (DeltaMAP) and HR (DeltaHR) elicited by electrical stimulation of the sciatic nerve (5-s trains of 100 pulses, 0.5-ms pulse duration, 100- to 400-microA pulse intensity) were significantly higher (ANOVA, P<0.05) in ZFR at each level of stimulus intensity. Regression analysis showed a linear increase in DeltaMAP and DeltaHR with increasing sciatic nerve stimulus intensity. Pressor responses to phenylephrine after ganglionic blockade demonstrated that vascular reactivity to adrenergic stimulation is not increased in ZFR compared with ZLR. Thus this factor does not contribute to enhancement of somatosympathetic reflexes observed in this strain. Insulin sensitivity in ZFR was one-fourth (P<0.05) that in ZLR. These results suggest that stronger sympathetic nervous reactivity in ZFR is associated with a severe insulin-resistant state before the onset of hypertension and support the hypothesis that insulin-mediated stimulation of the sympathetic nervous system is involved in the development of cardiovascular diseases related to alterations of glucose metabolism.

  18. Obesity Epidemiology

    PubMed Central

    Haidar, Yarah M.; Cosman, Bard C.

    2011-01-01

    Obesity has progressed in a few decades from a public health footnote in developed countries to a top-priority international issue. Because obesity implies increased morbidity and mortality from chronic, debilitating disorders, it is a major burden on individuals and health systems in both developing and developed countries. Obesity is a complex disorder unequally affecting all age groups and socioeconomic classes. Of special concern is increasing childhood obesity. This review presents the extent of the obesity epidemic and its impact worldwide by way of introduction to a discussion of colon and rectal surgery in the obese patient. PMID:23204935

  19. Obesity Downregulates MicroRNA-126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training

    PubMed Central

    Fernandes, Tiago; Soci, Ursula Paula Reno; Silveira, André Casanova; Barretti, Diego Lopes Mendes; Negrão, Carlos Eduardo

    2017-01-01

    Background. We investigated the effects of exercise training (ET) on miR-126 levels and skeletal muscle angiogenesis in obese Zucker rats. Results. Zucker rats were randomly assigned to sedentary and swimming-trained groups: lean sedentary (LS) and trained (LTR); obese sedentary (OB) and trained (OBTR). The OB group displayed capillary rarefaction compared with the LS group. In contrast, ET increased the capillary/fiber ratio by 38% in the LTR group and normalized capillary rarefaction in the OBTR group. VEGF, PI3K, and eNOS levels were reduced in the skeletal muscle of the OB group. ET normalized VEGF, PI3K, and eNOS levels in OBTR, contributing to vascular network homeostasis. PI3KR2 inhibits PI3K, a key mediator of the VEGF signaling pathway. Obesity decreased miR-126 and increased PI3KR2 levels compared with the LS group. However, ET normalized miR-126 levels in the OBTR group versus the LS group and decreased expression of PI3KR2. Conclusion. Our findings show that obesity leads to skeletal muscle capillary rarefaction, which is regulated by decreased miR-126 levels and increased PI3KR2. Inversely, ET normalizes miR-126 levels and VEGF signaling and should be considered an important therapeutic strategy for vascular disorders. PMID:28367267

  20. Melatonin administration in diabetes: regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats.

    PubMed

    Navarro-Alarcon, Miguel; Ruiz-Ojeda, Francisco J; Blanca-Herrera, Rosa M; Kaki, Abdullah; Adem, Abdu; Agil, Ahmad

    2014-03-01

    The use of melatonin, a neurohormone present in plants, represents an exciting approach for the maintenance of optimum health conditions. Melatonin administration ameliorates glucose homeostasis in Zucker diabetic fatty (ZDF) rats. The objective of this study was to investigate the effects of melatonin in diabetes in relation to the levels and regulation of plasma chromium (Cr), vanadium (V), and magnesium (Mg) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. At the age of 6 weeks, ZDF (n = 30) and ZL (n = 30) groups were each subdivided into three groups: control (C) (n = 10), vehicle-treated (V') (n = 10) and melatonin-treated (M) (10 mg kg(-1) per day; n = 10) groups for a 6 week period. After treatment, plasma mineral concentrations were measured by flame (Mg) and electrothermal (Cr and V) atomic absorption spectrometry. No significant differences were found between the C and V' groups (p > 0.05). Plasma Mg levels were significantly lower in C-ZDF vs. C-ZL rats, demonstrating the presence of hypomagnesemia in this diabetes mellitus model. Plasma V and Cr levels were significantly higher in M-ZDF vs. C-ZDF rats. Plasma Mg levels in ZDF rats were not affected by melatonin treatment (p > 0.05). Melatonin administration ameliorates the diabetic status of ZDF rats by enhancing plasma Cr and V concentrations. This appears to be the first report of a beneficial effect of melatonin treatment on plasma Cr and V regulation in ZDF rats.

  1. 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.…

  2. Obesity management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rates of obesity in the United States have increased dramatically over the past 30 years. Approximately 35% of children and 66% of adults are currently considered overweight or obese. Although obesity is seen in all ethnicities and economic classes, ethnic minorities and those of lower socioeconomic...

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

    PubMed Central

    Morettini, Micaela; Faelli, Emanuela; Perasso, Luisa; Fioretti, Sandro; Burattini, Laura

    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. PMID:28264067

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

    PubMed Central

    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.

  5. Obesity vaccines.

    PubMed

    Monteiro, Mariana P

    2014-01-01

    Obesity is one of the largest and fastest growing public health problems in the world. Last century social changes have set an obesogenic milieu that calls for micro and macro environment interventions for disease prevention, while treatment is mandatory for individuals already obese. The cornerstone of overweight and obesity treatment is diet and physical exercise. However, many patients find lifestyle modifications difficult to comply and prone to failure in the long-term; therefore many patients consider anti-obesity drugs an important adjuvant if not a better alternative to behavioral approach or obesity surgery. Since the pharmacological options for obesity treatment remain quite limited, this is an exciting research area, with new treatment targets and strategies on the horizon. This review discusses the development of innovative therapeutic agents, focusing in energy homeostasis regulation and the use of molecular vaccines, targeting hormones such as somatostatin, GIP and ghrelin, to reduce body weight.

  6. Childhood Obesity

    PubMed Central

    Ahmad, Qazi Iqbal; Ahmad, Charoo Bashir; Ahmad, Sheikh Mushtaq

    2010-01-01

    Obesity is increasing at an alarming rate throughout the world. Today it is estimated that there are more than 300 million obese people world-wide. Obesity is a condition of excess body fat often associated with a large number of debilitating and life-threatening disorders. It is still a matter of debate as to how to define obesity in young people. Overweight children have an increased risk of being overweight as adults. Genetics, behavior, and family environment play a role in childhood overweight. Childhood overweight increases the risk for certain medical and psychological conditions. Encourage overweight children to expand high energy activity, minimize low energy activity (screen watching), and develop healthful eating habits. Breast feeding is protective against obesity. Diet restriction is not recommended in very young children. Children are to be watched for gain in height rather than reduction in weight. Weight reduction of less than 10% is a normal variation, not significant in obesity. PMID:21448410

  7. Pioglitazone reverses down-regulation of cardiac PPAR{gamma} expression in Zucker diabetic fatty rats

    SciTech Connect

    Pelzer, Theo . E-mail: pelzer_t@klinik.uni-wuerzburg.de; Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Segerer, Stephan; Lichtenwald, Margit; Law, Marilyn P.; Schaefers, Michael; Ertl, Georg; Neyses, Ludwig

    2005-04-08

    Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPAR{gamma} in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPAR{gamma} agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPAR{gamma}, glucose transporter-4 and {alpha}-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPAR{gamma}, glut-4, and {alpha}-MHC expression levels in diabetic ZDF rats. Cardiac [{sup 18}F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPAR{gamma} agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPAR{gamma} expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin.

  8. Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic fatty rats

    PubMed Central

    SARIKAPHUTI, ARIYA; NARARATWANCHAI, THAMTHIWAT; HASHIGUCHI, TERUTO; ITO, TAKASHI; THAWORANUNTA, SITA; KIKUCHI, KIYOSHI; OYAMA, YOKO; MARUYAMA, IKURO; TANCHAROEN, SALUNYA

    2013-01-01

    The mulberry plant (Morus alba L.) contains abundant anthocyanins (ANCs), which are natural antioxidants. The aim of this study was to determine the ANC composition of Thai Morus alba L. fruits and to assess the effect of an ANC extract on blood glucose and insulin levels in male leptin receptor-deficient Zucker diabetic fatty (ZDF) rats. The major components of the ANC extract were identified by high-performance liquid chromatography-electrospray ionization-mass spectrometry. ZDF and lean rats were treated with 125 or 250 mg ANCs/kg body weight, or 1% carboxymethylcellulose (CMC) twice daily for 5 weeks. Neither ANC dose had an effect on body weight. Following 5 weeks of treatment, glucose levels were observed to increase from 105.5±8.7 to 396.25±21 mg/dl (P<0.0001) in the CMC-treated ZDF rats; however, the glucose levels were significantly lower in the rats treated with 125 or 250 mg/kg ANCs (228.25±45 and 131.75±10 mg/dl, respectively; P<0.001 versus CMC). The administration of 250 mg/kg ANCs normalized glucose levels in the ZDF rats towards those of the lean littermates. Insulin levels were decreased significantly in the ZDF rats treated with CMC or 125 mg/kg ANCs (P<0.0001), but not in the rats treated with 250 mg/kg ANCs. Histologically, 250 mg/kg ANCs was observed to prevent islet degeneration compared with the islets in CMC-treated rats. This study, demonstrated that ANCs extracted from Morus alba L. were well tolerated and exhibited effective anti-diabetic properties in ZDF rats. ANCs represent a promising class of therapeutic compounds that may be useful in the prevention of type 2 diabetes. PMID:24137248

  9. Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats.

    PubMed

    Warden, Craig H; Slupsky, Carolyn; Griffey, Stephen M; Bettaieb, Ahmed; Min, Esther; Le, Anh; Fisler, Janis S; Hansen, Susan; Haj, Fawaz; Stern, Judith S

    2014-01-01

    We previously reported that a congenic rat with Brown Norway (BN) alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC). Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by (1)H nuclear magnetic resonance (NMR) spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9-24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF) level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age.

  10. Cannabidiol improves vasorelaxation in Zucker diabetic fatty rats through cyclooxygenase activation.

    PubMed

    Wheal, Amanda J; Cipriano, Mariateresa; Fowler, Christopher J; Randall, Michael D; O'Sullivan, Saoirse Elizabeth

    2014-11-01

    Cannabidiol (CBD) decreases insulitis, inflammation, neuropathic pain, and myocardial dysfunction in preclinical models of diabetes. We recently showed that CBD also improves vasorelaxation in the Zucker diabetic fatty (ZDF) rat, and the objective of the present study was to establish the mechanisms underlying this effect. Femoral arteries from ZDF rats and ZDF lean controls were isolated, mounted on a myograph, and incubated with CBD (10 μM) or vehicle for 2 hours. Subsequent vasorelaxant responses were measured in combination with various interventions. Prostaglandin metabolites were detected using enzyme immunoassay. Direct effects of CBD on cyclooxygenase (COX) enzyme activity were measured by oxygraph assay. CBD enhanced the maximum vasorelaxation to acetylcholine (ACh) in femoral arteries from ZDF lean rats (P < 0.01) and especially ZDF rats (P < 0.0001). In ZDF arteries, this enhancement persisted after cannabinoid receptor (CB) type 1, endothelial CB, or peroxisome proliferator-activated receptor-γ antagonism but was inhibited by CB2 receptor antagonism. CBD also uncovered a vasorelaxant response to a CB2 agonist not previously observed. The CBD-enhanced ACh response was endothelium-, nitric oxide-, and hydrogen peroxide-independent. It was, however, COX-1/2- and superoxide dismutase-dependent, and CBD enhanced the activity of both purified COX-1 and COX-2. The CBD-enhanced ACh response in the arteries was inhibited by a prostanoid EP4 receptor antagonist. Prostaglandin E2 metabolite levels were below the limits of detection, but 6-keto prostaglandin F1 α was decreased after CBD incubation. These data show that CBD exposure enhances the ability of arteries to relax via enhanced production of vasodilator COX-1/2-derived products acting at EP4 receptors.

  11. Niacin-bound chromium increases life span in Zucker Fatty Rats.

    PubMed

    Preuss, Harry G; Echard, Bobby; Clouatre, Dallas; Bagchi, Debasis; Perricone, Nicholas V

    2011-10-01

    Avoiding insulin resistance (IR) associated with aging might lengthen life span based on previous studies using caloric-restricted animals. We assessed whether consuming niacin-bound chromium (NBC) alone or in a formula containing other so-called "insulin sensitizers" would overcome various manifestations of aging and extend life span in Zucker Fatty Rats (ZFR). We compared many metabolic parameters of ZFR fed NBC alone (n=12) or NBC in a unique formula (n=10) to a control group (n=10). In addition to NBC, the formula contained Allium sativum, Momordica charantia, Trigonella foenum-graecum and Gymnema sylvestre. The formula group received roughly 1/2 as much NBC daily as the NBC group. At week 44, all rats still lived, and no abnormalities in blood count (CBC), renal, or liver functions were found. In the two treatment groups compared to control, circulating glucose levels were significantly lower, with a trend toward lower HbA1C. Relatively elevated cholesterol and triglyceride concentrations occurred in the formula group. Compared to control, the NBC group had increased average lifespan (21.8%), median lifespan (14.1%), 30th percentile survival (19.6%), and maximum lifespan (22%). Despite similar beneficial effects on the glucose and blood pressure systems, a difference in aging was also found when the NBC group was compared to the formula group. When all rats in the other two groups had died, four in the NBC group continued to live at least a month longer. We attribute lack of a similar aging effect in the formula group to either lower dosing of NBC and/or that various ingredients in the formula counteracted the antiaging effect(s) of NBC.

  12. Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.

    PubMed

    Hill Gallant, Kathleen M; Gallant, Maxime A; Brown, Drew M; Sato, Amy Y; Williams, Justin N; Burr, David B

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.

  13. CHILDHOOD OBESITY

    PubMed Central

    Lakshman, Rajalakshmi; Elks, Cathy E.; Ong, Ken K.

    2013-01-01

    Clinical summary Childhood obesity has important consequences for health and wellbeing both during childhood and also in later adult life. The rising prevalence of childhood obesity poses a major public health challenge in both developed and developing countries by increasing the burden of chronic non-communicable diseases. Despite the urgent need for effective preventative strategies, there remains disagreement over its definition due to a lack of evidence on the optimal cut-offs linking childhood BMI to disease risks, and limited evidence on the most effective components of interventions to prevent childhood obesity. This article reviews the trends in childhood obesity, its genetic, nutritional and other risk factors, and preventative and treatment strategies. Particular emphasis is given to early-onset obesity in pre-school children, which, as a precursor to later childhood and adult obesity, provides insights into the developmental and genetic origins of obesity and also offers the potential for early preventative approaches with long-lasting benefits. PMID:23027812

  14. 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

  15. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat

    SciTech Connect

    Piteau, Shalea; Olver, Amy; Kim, Su-Jin; Winter, Kyle; Pospisilik, John Andrew; Lynn, Francis; Manhart, Susanne; Demuth, Hans-Ulrich; Speck, Madeleine; Pederson, Raymond A.; McIntosh, Christopher H.S.

    2007-11-03

    In type 2 diabetes (T2DM) {beta}-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 {+-} 3.8%) than ZF rats (48.8 {+-} 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 {+-} 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity.

  16. 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.

  17. Hormones and Obesity

    MedlinePlus

    ... Balance › Hormones and Obesity Fact Sheet Hormones and Obesity March, 2010 Download PDFs English Espanol Editors Caroline Apovian, MD Judith Korner, MD, PhD What is obesity? Obesity is a chronic (long-term) medical problem ...

  18. Glucose lowering effect of montbretin A in Zucker Diabetic Fatty rats.

    PubMed

    Yuen, Violet G; Coleman, John; Withers, Steven G; Andersen, Raymond J; Brayer, Gary D; Mustafa, Sally; McNeill, John H

    2016-01-01

    Diabetes is an increasingly prevalent disease state with a global impact. It is important that effective and cost-efficient methods be developed to treat this disease state. Zucker diabetic fatty rats, an animal model of type 2 diabetes, were treated with montbretin A (MbA), a selective human pancreatic α-amylase inhibitor, isolated from the corms of the Crocosmia crocosmiiflora plant that may have potential as a glucose-lowering agent. The study purpose was to determine if MbA was an orally effective treatment for diabetes. The effect of MbA was compared to a current clinical treatment modality, acarbose that is associated with gastrointestinal side effects known to affect patient compliance. MbA and acarbose were administered daily in the drinking water. Body weight and fluid intake were measured daily to calculate dose consumption. Plasma glucose levels were determined twice weekly in both the fed and fasted state. At termination samples were collected to assess increased risk of secondary complications related to diabetes and oxidative stress. There was no effect of either MbA or acarbose treatment on insulin levels. Plasma glucose levels were significantly lower following MbA treatment in the ZT group which persisted throughout the study period (day 49: 12.1 ± 1.2 mM). However, while there was an initial decrease in plasma glucose levels in the acarbose-treated fatty group, this effect was not sustained (day 49: 20.6 ± 1.3 mM) through to termination. MbA improved the oxidative status of the fatty diabetic animals as well as attenuated markers for increased risk of cardiovascular complications associated with diabetes. This study demonstrated that, at a lower dose as compared to acarbose (10 mg/kg/day), chronic oral administration of MbA (7.5 mg/kg/day) was an effective glucose-lowering agent in the treatment of type 2 diabetes.

  19. Melatonin ameliorates low-grade inflammation and oxidative stress in young Zucker diabetic fatty rats.

    PubMed

    Agil, Ahmad; Reiter, Russel J; Jiménez-Aranda, Aroa; Ibán-Arias, Ruth; Navarro-Alarcón, Miguel; Marchal, Juan Antonio; Adem, Abdu; Fernández-Vázquez, Gumersindo

    2013-05-01

    The aim of this study was to investigate the effects of melatonin on low-grade inflammation and oxidative stress in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups, each composed of 10 rats: naive (N), vehicle treated (V), and melatonin treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Pro-inflammatory state was evaluated by plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Also, oxidative stress was assessed by plasma lipid peroxidation (LPO), both basal and after Fe(2+)/H2O2 inducement. ZDF rats exhibited higher levels of IL-6 (112.4 ± 1.5 pg/mL), TNF-α (11.0 ± 0.1 pg/mL) and CRP (828 ± 16.0 µg/mL) compared with lean rats (IL-6, 89.9 ± 1.0, P < 0.01; TNF-α, 9.7 ± 0.4, P < 0.01; CRP, 508 ± 21.5, P < 0.001). Melatonin lowered IL-6 (10%, P < 0.05), TNF-α (10%, P < 0.05), and CRP (21%, P < 0.01). Basal and Fe(2+)/H2O2-induced LPO, expressed as malondialdehyde equivalents (µmol/L), were higher in ZDF rats (basal, 3.2 ± 0.1 versus 2.5 ± 0.1 in ZL, P < 0.01; Fe(2+)/H2O2-induced, 8.7 ± 0.2 versus 5.5 ± 0.3 in ZL; P < 0.001). Melatonin improved basal LPO (15%, P < 0.05) in ZDF rats, and Fe(2+)/H2O2- induced LPO in both ZL (15.2%, P < 0.01) and ZDF rats (39%, P < 0.001). These results demonstrated that oral melatonin administration ameliorates the pro-inflammatory state and oxidative stress, which underlie the development of insulin resistance and their consequences, metabolic syndrome, diabetes, and cardiovascular disease.

  20. Dehydroepiandrosterone (DHEA) Feeding Protects Liver Steatosis in Obese Breast Cancer Rat Model.

    PubMed

    Hakkak, Reza; Bell, Andrea; Korourian, Soheila

    2017-03-20

    Obesity is a major health problem in the US and globally. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, cancers, hyperlipidemia, and liver steatosis development. Dehydroepiandrosterone (DHEA) is a dietary supplement used as an anti-obesity supplement. Previously, we reported that DHEA feeding protects 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The objectives of this study were to investigate the effects of obesity and DHEA feeding on liver steatosis, body weight gain, and serum DHEA, DHEA sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) levels. Female Zucker rats were randomly assigned to either a control diet or a control diet with DHEA supplementation for 155 days. Livers were collected for histological examination. Serum was collected to measure DHEA, DHEA-S, IGF-1, and IGFBP-3. Our results show that DHEA-fed rats had significantly less liver steatosis (p < 0.001) than control-fed rats and gained less weight (p < 0.001). DHEA feeding caused significant decreases (p < 0.001) in the serum levels of IGF-1 and IGFBP-3 and significantly increased (p < 0.001) serum levels of DHEA and DHEA-S. Our results suggest that DHEA feeding can protect against liver steatosis by reducing body weight gain and modulating serum IGF-1 and IGFBP-3 levels in an obese breast cancer rat model.

  1. [Obesity paradox].

    PubMed

    Aursulesei, Viviana; Cozma, A; Datcu, M D

    2009-01-01

    Obesity has reached global epidemic proportions and is associated with major cardiovascular diseases and reduced overall survival. This paper reviews the metabolic and vascular consequences of dysfunctional adipocytokines in obesity as well as the pathological effects on blood pressure, cardiovascular structure and function. Despite this adverse association, numerous studies have documented an obesity paradox in which overweight and obese population with established cardiovascular disease have a better prognosis. There are potential explanations offered by literature for these puzzling data. For obese hypertensive patients the paradox is possibly linked to the lower systemic vascular resistance and plasma renin activity. In heart failure the excess body weight may confer some protective effects on mortality, due to a more metabolic reserve, higher levels of arterial pressure compatible with higher doses of cardioprotective medications, and a specific neuroendocrine profile with lower levels of circulating natriuretic atrial peptides, attenuated sympathetic nervous system and renin-angiotensin responses. For coronary heart disease and peripheral arterial disease the mechanisms are still uncertain. There are discussed a lesser severity of coronary lesions and left ventricular dysfunction, or a reduced prevalence of moderate-severe chronic obstructive pulmonary disease in patients selected for surgery. On the other hand, the constellation of data which supports purposeful weight reduction in the prevention and treatment of cardiovascular diseases, induces a controversial position regarding this new concept.

  2. TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats

    PubMed Central

    Zambad, Shitalkumar P; Munshi, Siralee; Dubey, Amita; Gupta, Ram; Busiello, Rosa Anna; Lanni, Antonia; Goglia, Fernando; Gupta, Ramesh C; Chauthaiwale, Vijay; Dutt, Chaitanya

    2011-01-01

    Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO) and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1) improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in liver and skeletal muscle, ultimately resulting in reduced hepatic as well as total body fat accumulation, as evaluated by magnetic resonance spectroscopy and magnetic resonance imaging, respectively. If reproduced in humans, these results could confirm that TRC150094 may represent an attractive therapeutic agent to counteract multiple residual cardiovascular risk components. PMID:21448317

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

    PubMed Central

    KOTOH, Jun; SASAKI, Daiki; MATSUMOTO, Kozo; MAEDA, Akihiko

    2016-01-01

    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. PMID:27523322

  4. Transcutaneous vagus nerve stimulation induces tidal melatonin secretion and has an antidiabetic effect in Zucker fatty rats.

    PubMed

    Wang, Shuxing; Zhai, Xu; Li, Shaoyuan; McCabe, Michael F; Wang, Xing; Rong, Peijing

    2015-01-01

    Melatonin plays a protective role in type 2 diabetes (T2D) through regulation of glucose metabolism. Whether transcutaneous vagus nerve stimulation (taVNS) is antidiabetic and whether a modulated melatonin production is involved in the antidiabetic mechanism of taVNS is unknown. In this study, once daily 30 min noninvasive taVNS was administered in Zucker diabetic fatty (ZDF, fa/fa) and Zucker lean (ZL, +/fa) littermates under anesthesia for 5 consecutive weeks. The acute and chronic influences of taVNS on the secretion of melatonin were studied as well as the effects of taVNS on blood glucose metabolism. We found that naïve ZDF rats develop hyperglycemia naturally with age. Each taVNS session would trigger a tidal secretion of melatonin both during and after the taVNS procedure and induce an acute two-phase glycemic change, a steep increase followed by a gradual decrease. Once daily taVNS sessions eventually reduced the glucose concentration to a normal level in seven days and effectively maintained the normal glycemic and plasma glycosylated hemoglobin (HbAlc) levels when applied for five consecutive weeks. These beneficial effects of taVNS also exist in pinealectomized rats, which otherwise would show overt and continuous hyperglycemia, hyperinsulinemia, and high HbAlc levels. We concluded that multiple taVNS sessions are antidiabetic in T2D through triggering of tidal secretion of melatonin. This finding may have potential importance in developing new approaches to the treatment of T2D, which is highly prevalent, incurable with any current approaches, and very costly to the world.

  5. 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.

  6. 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.

  7. Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models

    PubMed Central

    Della-Zuana, Odile; Audinot, Valérie; Levenez, Viviane; Ktorza, Alain; Presse, Françoise; Nahon, Jean-Louis; Boutin, Jean A.

    2012-01-01

    The compound S38151 is a nanomolar antagonist that acts at the melanin-concentrating hormone receptor 1 (MCH1). S38151 is more stable than its purely peptide counterpart, essentially because of the blockade of its N-terminus. Therefore, its action on various models of obesity was studied. Acute intra-cerebroventricular (i.c.v.) administration of S38151 in wild-type rats counteracted the effect of the stable precursor of melanin-concentrating hormone (MCH), NEI-MCH, in a dose-dependent manner (from 0.5 to 50 nmol/kg). In genetically obese Zucker fa/fa rats, daily i.c.v. administration of S38151 induced dose-dependent (5, 10, and 20 nmol/kg) inhibition of food intake, water intake, and body weight gain, as well as increased motility (maximal effect observed at 20 nmol/kg). In Zucker fa/fa rats, intraperitoneal injection of S38151 (30 mg/kg) induced complete inhibition of food consumption within 1 h. Daily intraperitoneal injection of S38151 (10 and 30 mg/kg) into genetically obese ob/ob mice or diet-induced obese mice is able to limit body weight gain. Furthermore, S38151 administration (10 and 30 mg/kg) does not affect food intake, water intake, or body weight gain in MCHR1-deleted mice, demonstrating that its effects are linked to its interaction with MCH1. These results validate MCH1 as a target of interest in obesity. S38151 cannot progress to the clinical phase because it is still too poorly stable in vivo. PMID:23267345

  8. Obesity & osteoarthritis.

    PubMed

    King, Lauren K; March, Lyn; Anandacoomarasamy, Ananthila

    2013-01-01

    The most significant impact of obesity on the musculoskeletal system is associated with osteoarthritis (OA), a disabling degenerative joint disorder characterized by pain, decreased mobility and negative impact on quality of life. OA pathogenesis relates to both excessive joint loading and altered biomechanical patterns together with hormonal and cytokine dysregulation. Obesity is associated with the incidence and progression of OA of both weight-bearing and non weight-bearing joints, to rate of joint replacements as well as operative complications. Weight loss in OA can impart clinically significant improvements in pain and delay progression of joint structural damage. Further work is required to determine the relative contributions of mechanical and metabolic factors in the pathogenesis of OA.

  9. Glucomannan and glucomannan plus spirulina added to pork significantly block dietary cholesterol effects on lipoproteinemia, arylesterase activity, and CYP7A1 expression in Zucker fa/fa rats.

    PubMed

    González-Torres, Laura; Vázquez-Velasco, Miguel; Olivero-David, Raúl; Bastida, Sara; Benedí, Juana; González, Rafaela Raposo; González-Muñoz, Ma José; Sánchez-Muniz, Francisco J

    2015-12-01

    Zucker fa/fa rats easily develop dyslipidemia and obesity. Restructured pork (RP) is a suitable matrix for including functional ingredients. The effects of glucomannan- RP or glucomannan plus spirulina-enriched RP on plasma lipid/lipoprotein levels, cytochrome P450 7A1 (CYP7A1) expression, and arylesterase activity in growing fa/fa rats fed high-energy, high-fat cholesterol-enriched diets were tested. Groups of six rats each received diet containing 15% control-RP (C), 15% glucomannan-RP diet (G), 15% glucomannan + spirulina-RP diet (GS), and same diets enriched with 2.4% cholesterol and 0.49% cholic acid (cholesterol-enriched control (HC), cholesterol-enriched glucomannan (HG), and cholesterol-enriched glucomannan + spirulina (HGS) diets) over a 7-week period. C diet induced obesity, severe hyperglycemia, moderate hypercholesterolemia, and hypertriglyceridemia. Those facts were not significantly modified by G or GS diets. G diet increased CYP7A1 expression but decreased the total cholesterol/high density lipoproteins (HDL)-cholesterol ratio (p < 0.05) vs. C diet. GS vs. G diet increased (p < 0.05) CYP7A1 expression. HC vs. C diet reduced food intake, body weight gain, and plasma glucose (p < 0.01) but increased cholesterolemia (p < 0.01), lipidemia (plasma cholesterol plus triglycerides) (p < 0.001), cholesterol/triglyceride ratio in very low density lipoproteins (VLDL), and HDL (p < 0.05), cholesterol transported by VLDL and intermediate density lipoproteins (IDL) + low density lipoproteins (LDL), total cholesterol/HDL-cholesterol ratio and CYP7A1 expression (at least p < 0.05). HG and HGS diets vs. HC noticeably reduced lipidemia (p < 0.001), normalized VLDL and IDL + LDL lipid composition, and increased CYP7A1 expression (p < 0.01) but did not modify the cholesterol/HDL-cholesterol ratio. HGS vs. HG decreased triglyceridemia, the triglyceride-glucose (TyG) index and increased arylesterase/HDL-cholesterol activity (p < 0

  10. Therapeutic Effect of Vagus Nerve Stimulation on Depressive-Like Behavior, Hyperglycemia and Insulin Receptor Expression in Zucker Fatty Rats

    PubMed Central

    Rong, Peijing; McCabe, Michael F.; Wang, Xing; Zhao, Jingjun; Ben, Hui; Wang, Shuxing

    2014-01-01

    Depression and type 2 diabetes (T2D) are common comorbid diseases and highly prevalent in the clinical setting with an unclarified mechanism. Zucker diabetic fatty (ZDF, fa/fa) rats natively develop T2D with hyperglycemia and hyperinsulinemia. Here we studied whether ZDF rats also innately develop depression, what a correlation is between depression and T2D, whether insulin receptor (IR) expression is involved in, and whether transcutaneous auricular vagus nerve stimulation (taVNS) would be beneficial in amelioration of the comorbidity. Six week old male ZDF and Zucker lean (ZL, fa/+) littermates were randomly divided into naïve (ZDF, n = 6; ZL, n = 7) and taVNS (ZDF-taVNS, n = 8; ZL-taVNS, n = 6) groups. Once daily 30 min-taVNS sessions were administrated under anesthesia for 34 consecutive days in taVNS groups. Blood glucose levels were tested weekly, and plasma glycosylated hemoglobin (HbAlc) level and immobility time in forced swimming test were determined on day 35 in all groups. The expression of insulin receptor (IR) in various tissues was also detected by immunostaining and Western blot. We found that naïve ZDF rats developed hyperglycemia steadily. These ZDF rats showed a strong positive correlation between longer immobility time and higher plasma HbAlC level. Long term taVNS treatment simultaneously prevented the development of depression-like behavior and progression of hyperglycemia in ZDF rats. The expression of IR in various tissues of naïve ZDF rats is lower than in naïve ZL and long-term taVNS treated ZDF rats. Collectively, our results indicate that in ZDF rats, i) depression and T2D develop simultaneously, ii) immobility time and HbAlc concentrations are highly and positively correlated, iii) a low expression of IR may be involved in the comorbidity of depression and T2D, and iv) taVNS is antidiabetic and antidepressive possibly through IR expression upregulation. PMID:25365428

  11. Trans-10,cis-12-conjugated linoleic acid worsens renal pathology and alters cyclooxygenase derived oxylipins in obesity-associated nephropathy.

    PubMed

    Zhan, Yang; Shi, Hong; Caligiuri, Stephanie P B; Wu, Yinghong; Declercq, Vanessa; Taylor, Carla G; Zahradka, Peter; Ogborn, Malcolm R; Aukema, Harold M

    2015-02-01

    Dietary conjugated linoleic acid (CLA) reduces indicators of early renal disease progression and the associated elevated cyclooxygenase (COX) levels in young obese rats with obesity-associated nephropathy (OAN). Therefore, renal function and injury and COX and its metabolites were assessed in obese fa/fa Zucker rats with more advanced renal disease. Obese rats at 16 weeks of age were provided with either cis(c)9, trans(t)11 (fa/fa-9,11) or t10,c12 (fa/fa-10,12) CLA for 8 weeks, and compared to lean (lean-CTL) and obese (fa/fa-CTL) rats provided the control diet without CLA. Obese rats displayed significantly reduced renal function and increased renal injury compared to lean rats. In the obese rat groups, glomerular hypertrophy was reduced in both CLA-supplemented groups. While all other measures of renal function or injury were not different in fa/fa-9,11 compared to fa/fa-CTL rats, the fa/fa-10,12 rats had greater renal hypertrophy, glomerular fibrosis, fibrosis, tubular casts and macrophage infiltration compared to the fa/fa-CTL and fa/fa-9,11 groups. The fa/fa-10,12 group also had elevated levels of renal COX1, which was associated with increased levels of two oxylipins produced by this enzyme, 6-keto-prostaglandin F(1α), and thromboxane B₂. Renal linoleic acid and its lipoxygenase products also were lower in obese compared to lean rats, but CLA supplementation had no effect on these or any other lipoxygenase oxylipins. In summary, supplementation with c9,t11 CLA did not improve more advanced OAN and t10,c12 CLA worsened the renal pathology. Altered production of select COX1 derived oxylipins was associated with the detrimental effect of the t10,c12 isomer.

  12. Urinary Metabolomic Profiling in Zucker Diabetic Fatty Rats with Type 2 Diabetes Mellitus Treated with Glimepiride, Metformin, and Their Combination.

    PubMed

    Dong, Yu; Chen, Yi-Tao; Yang, Yuan-Xiao; Shou, Dan; Li, Chang-Yu

    2016-10-31

    Type 2 diabetes mellitus (T2DM) is a high incidence metabolic disease. Glimepiride, metformin, and their combination are the most commonly used therapeutics for T2DM in the clinic, but little is known about the metabolic responses of these therapies. In this study, ultrahigh-pressure liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-QTOF-MS)-based metabolomics was applied to detect changes in the urinary metabolomic profile of Zucker diabetic fatty (ZDF) rats in response to these treatments. Additionally, standard biochemical parameters (e.g., fasting plasma glucose, glycosylated hemoglobin, oral glucose tolerance, urinary glucose, triglyceride, total cholesterol, and insulin) and liver histopathology were monitored and observed. Six metabolites, including 3-galactosyl lactose, citric acid, sphingosine, phytosphingosine, ribothymidine, and succinoadenosine, were found significantly reverted to the normal level after these therapies. The present study is the first to present citric acid and sphinganine as the potential markers of T2DM, which could be used as indicators to observe the anti-diabetic effects of glimepiride, metformin, and their combination treatments.

  13. 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

    2017-01-12

    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.

  14. Changes in renal vessels associated with long-term administration of angiotensin converting enzyme inhibitor in Zucker fatty rats

    PubMed Central

    Nakanishi, Kazushige; Nagai, Yohko; Akimoto, Tatsuo; Yamanaka, Nobuaki

    2017-01-01

    Background Recently, we showed that long-term angiotensin receptor blocker (ARB) administration induced unusual proliferative changes in smooth muscle cells (SMCs) of afferent arterioles of the kidneys of Zucker fatty rats (ZFRs). In this study, we investigated renal afferent arteriolar changes induced by the long-term administration of an angiotensin converting enzyme inhibitor (ACEI) in ZFRs. Materials and Methods Fourteen 6-week-old male ZFRs were divided into two groups (n=14): the ZFR+ACEI group (n=6) was fed a standard diet containing ACEI (Enalapril, 2 mg/kg/day), and the ZFR control group (n=8) for 12 weeks. Blood pressure and proteinuria were examined and morphological studies on kidneys were performed. Results Remarkable proliferative changes in the afferent arteriolar SMCs were frequently observed in the group given ACEI; (66.1 ± 12.9%) compared with the control group (1.77 ± 1.56%, P<0.001). Conclusions It was indicated that long-term ACEI administration induced unusual proliferative changes in SMCs in afferent arterioles of ZFRs. These changes could reduce intraglomerular pressure by narrowing the lumens of afferent arterioles, but they could cause irreversible damage to the arterioles. PMID:28260705

  15. Effects of intracerebroventricularly and intraperitoneally administered growth hormone on body weight and food intake in fa/fa Zucker rats.

    PubMed

    Schulz, Carla; Wieczorek, Ingo; Reschke, Kirsten; Lehnert, Hendrik

    2002-01-01

    Growth hormone (GH) possesses multiple metabolic effects, in particular with regard to glucose and lipid homeostasis. Studies on the effects of GH on body weight and food and water intake are scarce and have yielded controversial results. We investigated the effects of different modes of GH administration on the parameters of body weight and food intake as well as on insulin and leptin concentrations in fa/fa Zucker rats. In control experiments, aqua pro injection was given. GH was administered over a time period of 11 days at a daily dose of 250 microg intraperitoneally (i.p.) and 25 microg intracerebroventricularly (i.c.v.). While both food intake and body weight were found to be unaltered in the four groups after this observation period, there was an enhanced food intake and consecutively an increase in body weight over the day period when compared to the night period in the groups of rats that received GH i.c.v. or i.p. This tendency was also shown for water intake. Insulin and leptin concentrations were similar in all groups. Thus, injection of GH appears to modify food intake-related behavior, since the periods of enhanced food and water intake were shifted from night- to daytime. Thus, while in general the metabolic parameters remained unchanged, the activity pattern was clearly modified.

  16. A metabolomics-driven elucidation of the anti-obesity mechanisms of xanthohumol.

    PubMed

    Kirkwood, Jay S; Legette, LeeCole L; Miranda, Cristobal L; Jiang, Yuan; Stevens, Jan F

    2013-06-28

    Mild, mitochondrial uncoupling increases energy expenditure and can reduce the generation of reactive oxygen species (ROS). Activation of cellular, adaptive stress response pathways can result in an enhanced capacity to reduce oxidative damage. Together, these strategies target energy imbalance and oxidative stress, both underlying factors of obesity and related conditions such as type 2 diabetes. Here we describe a metabolomics-driven effort to uncover the anti-obesity mechanism(s) of xanthohumol (XN), a prenylated flavonoid from hops. Metabolomics analysis of fasting plasma from obese, Zucker rats treated with XN revealed decreases in products of dysfunctional fatty acid oxidation and ROS, prompting us to explore the effects of XN on muscle cell bioenergetics. At low micromolar concentrations, XN acutely increased uncoupled respiration in several different cell types, including myocytes. Tetrahydroxanthohumol also increased respiration, suggesting electrophilicity did not play a role. At higher concentrations, XN inhibited respiration in a ROS-dependent manner. In myocytes, time course metabolomics revealed acute activation of glutathione recycling and long term induction of glutathione synthesis as well as several other changes indicative of short term elevated cellular stress and a concerted adaptive response. Based on these findings, we hypothesize that XN may ameliorate metabolic syndrome, at least in part, through mitochondrial uncoupling and stress response induction. In addition, time course metabolomics appears to be an effective strategy for uncovering metabolic events that occur during a stress response.

  17. A Metabolomics-driven Elucidation of the Anti-obesity Mechanisms of Xanthohumol*

    PubMed Central

    Kirkwood, Jay S.; Legette, LeeCole L.; Miranda, Cristobal L.; Jiang, Yuan; Stevens, Jan F.

    2013-01-01

    Mild, mitochondrial uncoupling increases energy expenditure and can reduce the generation of reactive oxygen species (ROS). Activation of cellular, adaptive stress response pathways can result in an enhanced capacity to reduce oxidative damage. Together, these strategies target energy imbalance and oxidative stress, both underlying factors of obesity and related conditions such as type 2 diabetes. Here we describe a metabolomics-driven effort to uncover the anti-obesity mechanism(s) of xanthohumol (XN), a prenylated flavonoid from hops. Metabolomics analysis of fasting plasma from obese, Zucker rats treated with XN revealed decreases in products of dysfunctional fatty acid oxidation and ROS, prompting us to explore the effects of XN on muscle cell bioenergetics. At low micromolar concentrations, XN acutely increased uncoupled respiration in several different cell types, including myocytes. Tetrahydroxanthohumol also increased respiration, suggesting electrophilicity did not play a role. At higher concentrations, XN inhibited respiration in a ROS-dependent manner. In myocytes, time course metabolomics revealed acute activation of glutathione recycling and long term induction of glutathione synthesis as well as several other changes indicative of short term elevated cellular stress and a concerted adaptive response. Based on these findings, we hypothesize that XN may ameliorate metabolic syndrome, at least in part, through mitochondrial uncoupling and stress response induction. In addition, time course metabolomics appears to be an effective strategy for uncovering metabolic events that occur during a stress response. PMID:23673658

  18. [Obesity and cancer].

    PubMed

    Salaün, Hélène; Thariat, Juliette; Vignot, Marina; Merrouche, Yacine; Vignot, Stéphane

    2017-01-01

    The proportion of people affected by obesity is increasing and this finding emphasizes several issues in oncology: obesity as a risk factor for cancer, prognostic value of obesity in cancer patients, nutritional assessment in overweight patients and impact of obesity on treatment management. It is important to remember the common underevaluation of malnutrition in overweight or obese patients. Every caregiver must be especially careful about the management of comorbidities in these patients.

  19. 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.

  20. Role of PP2C in cardiac lipid accumulation in obese rodents and its prevention by troglitazone.

    PubMed

    Wang, May-yun; Unger, Roger H

    2005-01-01

    In obese rodents, excess myocardial lipid accumulation (lipotoxicity) of myocardium may cause cardiomyopathy that in the obese Zucker diabetic fatty (ZDF) fa/fa rat can be prevented by treatment with troglitazone (TGZ). To determine the underlying mechanisms, we measured total 5'-AMP-activated kinase (AMPK) protein and its activated, phosphorylated form, P-AMPK. P-AMPK was significantly reduced in both ZDF fa/fa rat and ob/ob mouse hearts compared with lean, wild-type controls. TGZ treatment of obese ZDF rats, which lowered cardiac lipid content, increased P-AMPK. Expression of protein phosphatase 2C (PP2C), which inactivates AMPK activity by dephosphorylation, was increased in untreated ZDF fa/fa rat hearts, but fell with TGZ treatment, suggesting that PP2C can influence AMPK activity. In cultured myocardiocytes, fatty acids reduced P-AMPK, suggesting a feed-forward effect of lipid overload. Our findings highlight a role of PP2C and AMPK in the derangements of cardiac lipid metabolism in obesity and provide new insights as to the mechanisms of the liporegulatory disorder leading to lipotoxic cardiomyopathy.

  1. 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.

  2. [Obesity in childhood].

    PubMed

    Shcherbakova, M Iu; Poriagina, G I; Kovaleva, E A

    2010-01-01

    In this article presented modern data on the definition of obesity in childhood and its prevalence. Were reflected the basic diagnostic criteria for obesity and metabolic syndrome. Were analyzed genetic changes, hormonal factors, influence lifestyle of modern man as the reasons of the obesity. Are also was considered data on the relation of obesity and its complications such as cardiovascular, metabolic syndromes, nonalcoholic fatty liver disease. Was reflected the views of various specialists (cardiologists, endocrinologists, gastroenterologists, pediatricians) to the problem of overweight and obesity in children and adolescents. Were presented modern data on the approaches to the treatment of obesity in children.

  3. Cardiac and renal function are progressively impaired with aging in Zucker diabetic fatty type II diabetic rats.

    PubMed

    Baynes, John; Murray, David B

    2009-01-01

    This study investigated the temporal relationship between cardiomyopathy and renal pathology in the type II diabetic Zucker diabetic fatty (ZDF) rat. We hypothesized that changes in renal function will precede the development of cardiac dysfunction in the ZDF rat. Animals (10 weeks old) were divided into four experimental groups: Lean Control (fa/?) LC(n = 7), untreated ZDF rats (n = 7) sacrificed at 16 weeks of age, and LC (n = 7) untreated ZDF rats (n = 9) sacrificed at 36 weeks of age. LV structural/functional parameters were assessed via Millar conductance catheter. Renal function was evaluated via markers of proteinuria and evidence of hydronephrosis. LV mass was significantly less in the ZDF groups at both time points compared to age-matched LC. End diastolic volume was increased by 16% at 16 weeks and by 37% at 36 weeks of age (p < 0.05 vs. LC). End diastolic pressure and end systolic volume were significantly increased (42% and 27%respectively) at 36 weeks of age in the ZDF compared to LC. Kidney weights were significantly increased at both 16 and 36 week in ZDF animals (p < 0.05 vs. LC). Increased urinary albumin and decreased urinary creatinine were paralleled by a marked progression in the severity of hydronephrosis from 16 to 36 weeks of age in the ZDF group. In summary, there is evidence of progressive structural and functional changes in both the heart and kidney, starting as early as 16 weeks,without evidence that one pathology precedes or causes the other in the ZDF model of type II diabetes.

  4. Effect of Isoflurane on Myocardial Energetic and Oxidative Stress in Cardiac Muscle from Zucker Diabetic Fatty Rat

    PubMed Central

    Shen, Xiaoxu; Bhatt, Niraj; Xu, Jianhong; Meng, Tao; Aon, Miguel A.; O’Rourke, Brian; Berkowitz, Dan E.; Cortassa, Sonia

    2014-01-01

    The effect of inhalational anesthetics on myocardial contraction and energetics in type 2 diabetes mellitus is unknown. We investigated the effect of isoflurane (ISO) on force and intracellular Ca2+ transient (iCa), myocardial oxygen consumption (MVo2), and energetics/redox behavior in trabecular muscles from Zucker diabetic fatty (ZDF) rats. At baseline, force and corresponding iCa were lower in ZDF trabeculae than in controls. ISO decreased force in both groups in a dose-dependent manner. ISO did not affect iCa amplitude in controls, but ISO > 1.5% significantly reduced iCa amplitude in ZDF trabeculae. ISO-induced force depression fully recovered as a result of increased iCa when external Ca2+ was raised in controls. However, both force and iCa remained low in ZDF muscle at elevated external Ca2+. In controls, force, iCa, and MVo2 increased when stimulation frequency was increased from 0.5 to 1.5 Hz. ZDF muscles, however, exhibited blunted responses in force and iCa and decreased MVo2. Oxidative stress levels were unchanged in control muscles but increased significantly in ZDF muscles after exposure to ISO. Finally, the depressive effect of ISO was prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) in ZDF muscles. These findings suggest that ISO dose-dependently attenuates force in control and ZDF muscles with differential effect on iCa. The mechanism of force depression by ISO in controls is mainly decreased myofilament Ca2+ sensitivity, whereas in ZDF muscles the ISO-induced decrease in contraction is due to worsening oxidative stress, which inhibits iCa and force development. PMID:24431470

  5. Analysis of the effect of canagliflozin on renal glucose reabsorption and progression of hyperglycemia in zucker diabetic Fatty rats.

    PubMed

    Kuriyama, Chiaki; Xu, Jun Zhi; Lee, Seunghun Paul; Qi, Jenson; Kimata, Hirotaka; Kakimoto, Tetsuhiro; Nakayama, Keiko; Watanabe, Yoshinori; Taniuchi, Nobuhiko; Hikida, Kumiko; Matsushita, Yasuaki; Arakawa, Kenji; Saito, Akira; Ueta, Kiichiro; Shiotani, Masaharu

    2014-11-01

    Sodium-glucose cotransporter 2 (SGLT2) plays a major role in renal glucose reabsorption. To analyze the potential of insulin-independent blood glucose control, the effects of the novel SGLT2 inhibitor canagliflozin on renal glucose reabsorption and the progression of hyperglycemia were analyzed in Zucker diabetic fatty (ZDF) rats. The transporter activity of recombinant human and rat SGLT2 was inhibited by canagliflozin, with 150- to 12,000-fold selectivity over other glucose transporters. Moreover, in vivo treatment with canagliflozin induced glucosuria in mice, rats, and dogs in a dose-dependent manner. It inhibited apparent glucose reabsorption by 55% in normoglycemic rats and by 94% in hyperglycemic rats. The inhibition of glucose reabsorption markedly reduced hyperglycemia in ZDF rats but did not induce hypoglycemia in normoglycemic animals. The change in urinary glucose excretion should not be used as a marker to predict the glycemic effects of this SGLT2 inhibitor. In ZDF rats, plasma glucose and HbA1c levels progressively increased with age, and pancreatic β-cell failure developed at 13 weeks of age. Treatment with canagliflozin for 8 weeks from the prediabetic stage suppressed the progression of hyperglycemia, prevented the decrease in plasma insulin levels, increased pancreatic insulin contents, and minimized the deterioration of islet structure. These results indicate that selective inhibition of SGLT2 with canagliflozin controls the progression of hyperglycemia by inhibiting renal glucose reabsorption in ZDF rats. In addition, the preservation of β-cell function suggests that canagliflozin treatment reduces glucose toxicity via an insulin-independent mechanism.

  6. Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats

    PubMed Central

    Delic, Denis; Eisele, Claudia; Schmid, Ramona; Luippold, Gerd; Mayoux, Eric; Grempler, Rolf

    2016-01-01

    The aim of the present pilot study was the identification of micro-RNA changes over time during the development and progression of type 2 diabetes (T2D) in Zucker diabetic fatty rats (ZDF rats). T2D is a complex metabolic disorder that is characterized, inter alia, by progressive failure of pancreatic β cells to produce insulin, but also by functional or morphological modifications of others organ, such as liver, adipose tissue and the cardiovascular system. Micro-RNAs are a novel class of biomarkers that have the potential to represent biomarkers of disease progression. In this study, the onset and progression of diabetes was followed in ZDF rats from six weeks until 17 weeks of age. After an initial phase of hyperinsulinemia, the animals developed T2D and lost the capacity to produce sufficient insulin. Circulating miRNAs were measured from plasma samples at four time points: pre-diabetes (six weeks of age), hyperinsulinemia (eight weeks), β cell failure (11 weeks) and late-stage diabetes (17 weeks) using TaqMan miRNA arrays. Bioinformatic analysis revealed distinct changes of circulating miRNAs over time. Several miRNAs were found to be increased over the course of the disease progression, such as miR-122, miR-133, miR-210 and miR-375. The most significantly decreased miRNAs were miR-140, miR-151-3p, miR-185, miR-203, miR-434-3p and miR-450a. Some of the miRNAs have also been identified in type 2 diabetic patients recently and, therefore, may have the potential to be useful biomarkers for the disease progression of T2D and/or the treatment response for anti-diabetic medications. PMID:27153060

  7. Impact of alogliptin and pioglitazone on lipid metabolism in islets of prediabetic and diabetic Zucker Diabetic Fatty rats.

    PubMed

    Cai, Ying; Lydic, Todd A; Turkette, Thomas; Reid, Gavin E; Olson, L Karl

    2015-05-01

    Prolonged exposure of pancreatic beta (β) cells to elevated glucose and free fatty acids (FFA) as occurs in type 2 diabetes results in loss of β cell function and survival. In Zucker Diabetic Fatty (ZDF) rats, β cell failure is associated with increased triacylglyceride (TAG) synthesis and disruption of the glycerolipid/FFA (GL/FFA) cycle, a critical arm of glucose-stimulated insulin secretion (GSIS). The aim of this study was to determine the impact of activation of PPARγ and increased incretin action via dipeptidyl-peptidase inhibition using pioglitazone and/or alogliptin, respectively, on islet lipid metabolism in prediabetic and diabetic ZDF rats. Transition of control prediabetic ZDF rats to diabetes was associated with reduced plasma insulin levels, reduced islet insulin content and GSIS, reduced stearoyl-CoA desaturase 2 (SCD 2) expression, and increased islet TAG, diacylglyceride (DAG) and ceramides species containing saturated FA. Treatment of prediabetic ZDF rats with a combination of pioglitazone and alogliptin, but not individually, prevented the transition to diabetes and was associated with marked lowering of islet TAG and DAG levels. Pioglitazone and alogliptin, however, did not restore SCD2 expression, the degree of FA saturation in TAG, DAG or ceramides, islet insulin content, or lower ceramide levels. These findings are consistent with activation of PPARγ and increased incretin action working in concert to restore GL/FFA cycle in β cells of ZDF rats. Restoration of the GL/FFA cycle without correcting islet FA desaturation, production of islet ceramides, and/or insulin sensitivity, however, may place these islets at risk for β cell failure.

  8. 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.

  9. Metformin Protects Kidney Cells From Insulin-Mediated Genotoxicity In Vitro and in Male Zucker Diabetic Fatty Rats.

    PubMed

    Othman, Eman Maher; Oli, R G; Arias-Loza, Paula-Anahi; Kreissl, Michael C; Stopper, Helga

    2016-02-01

    Hyperinsulinemia is thought to enhance cancer risk. A possible mechanism is induction of oxidative stress and DNA damage by insulin, Here, the effect of a combination of metformin with insulin was investigated in vitro and in vivo. The rationales for this were the reported antioxidative properties of metformin and the aim to gain further insights into the mechanisms responsible for protecting the genome from insulin-mediated oxidative stress and damage. The comet assay, a micronucleus frequency test, and a mammalian gene mutation assay were used to evaluate the DNA damage produced by insulin alone or in combination with metformin. For analysis of antioxidant activity, oxidative stress, and mitochondrial disturbances, the cell-free ferric reducing antioxidant power assay, the superoxide-sensitive dye dihydroethidium, and the mitochondrial membrane potential-sensitive dye 5,5',6,6'tetrachloro-1,1',3,3'-tetraethylbenzimidazol-carbocyanine iodide were applied. Accumulation of p53 and pAKT were analyzed. As an in vivo model, hyperinsulinemic Zucker diabetic fatty rats, additionally exposed to insulin during a hyperinsulinemic-euglycemic clamp, were treated with metformin. In the rat kidney samples, dihydroethidium staining, p53 and pAKT analysis, and quantification of the oxidized DNA base 8-oxo-7,8-dihydro-2'-deoxyguanosine were performed. Metformin did not show intrinsic antioxidant activity in the cell-free assay, but protected cultured cells from insulin-mediated oxidative stress, DNA damage, and mutation. Treatment of the rats with metformin protected their kidneys from oxidative stress and genomic damage induced by hyperinsulinemia. Metformin may protect patients from genomic damage induced by elevated insulin levels. This may support efforts to reduce the elevated cancer risk that is associated with hyperinsulinemia.

  10. Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats.

    PubMed

    Delic, Denis; Eisele, Claudia; Schmid, Ramona; Luippold, Gerd; Mayoux, Eric; Grempler, Rolf

    2016-05-03

    The aim of the present pilot study was the identification of micro-RNA changes over time during the development and progression of type 2 diabetes (T2D) in Zucker diabetic fatty rats (ZDF rats). T2D is a complex metabolic disorder that is characterized, inter alia, by progressive failure of pancreatic β cells to produce insulin, but also by functional or morphological modifications of others organ, such as liver, adipose tissue and the cardiovascular system. Micro-RNAs are a novel class of biomarkers that have the potential to represent biomarkers of disease progression. In this study, the onset and progression of diabetes was followed in ZDF rats from six weeks until 17 weeks of age. After an initial phase of hyperinsulinemia, the animals developed T2D and lost the capacity to produce sufficient insulin. Circulating miRNAs were measured from plasma samples at four time points: pre-diabetes (six weeks of age), hyperinsulinemia (eight weeks), β cell failure (11 weeks) and late-stage diabetes (17 weeks) using TaqMan miRNA arrays. Bioinformatic analysis revealed distinct changes of circulating miRNAs over time. Several miRNAs were found to be increased over the course of the disease progression, such as miR-122, miR-133, miR-210 and miR-375. The most significantly decreased miRNAs were miR-140, miR-151-3p, miR-185, miR-203, miR-434-3p and miR-450a. Some of the miRNAs have also been identified in type 2 diabetic patients recently and, therefore, may have the potential to be useful biomarkers for the disease progression of T2D and/or the treatment response for anti-diabetic medications.

  11. Enhanced amylin-mediated body weight loss in estradiol-deficient diet-induced obese rats.

    PubMed

    Trevaskis, James L; Turek, Victoria F; Wittmer, Carrie; Griffin, Peter S; Wilson, Julie K; Reynolds, James M; Zhao, Yu; Mack, Christine M; Parkes, David G; Roth, Jonathan D

    2010-12-01

    In rodents, ovariectomy (OVX) elicits weight gain and diminished responsiveness to homeostatic signals. Here we characterized the response of obese OVX rats to peripheral amylin. Rats received sham surgery (SHAM), OVX, or OVX with hormonal replacement (17β-estradiol, 2 μg per 4 d; OVX+E) and were infused with vehicle or amylin (50 μg/kg · d) for 28 d. Amylin reduced body weight (5.1 ± 1.1%) and food intake (10.9 ± 3.4%) in SHAM rats but was twice as efficacious in OVX rats in reducing weight (11.2 ± 1.9%) and food intake (23.0 ± 2.0%). There were no differences between amylin-treated SHAM and OVX+E rats. OVX decreased metabolic rate (∼24%) and increased respiratory exchange ratio relative to SHAM. Amylin partially normalized metabolic rate (13% increase) in OVX rats and decreased respiratory exchange ratio in OVX and SHAM rats. Regarding central mechanisms, amylin infusion corrected the OVX-induced decrease in hippocampal neurogenesis and increased immobility in the forced swim test. Additionally, amylin increased neurogenesis (∼2-fold) within the area postrema of OVX rats. To assess the contribution of endogenous leptin to amylin-mediated weight loss in OVX rats, amylin was administered to SHAM or OVX Zucker diabetic fatty rats. In SHAM rats, amylin infusion reduced food intake but not body weight, whereas in OVX Zucker diabetic fatty rats, food intake, body weight, and insulin were reduced. Overall, amylin induced greater body weight loss in the absence of estradiol via central and peripheral actions that did not require leptin. These findings support the clinical investigation of amylin in low estradiol (e.g. postmenopausal) states.

  12. Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.

    PubMed

    Agil, Ahmad; El-Hammadi, Mazen; Jiménez-Aranda, Aroa; Tassi, Mohamed; Abdo, Walied; Fernández-Vázquez, Gumersindo; Reiter, Russel J

    2015-08-01

    Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic-induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity.

  13. Insulin-induced generation of reactive oxygen species and uncoupling of nitric oxide synthase underlie the cerebrovascular insulin resistance in obese rats.

    PubMed

    Katakam, Prasad V G; Snipes, James A; Steed, Mesia M; Busija, David W

    2012-05-01

    Hyperinsulinemia accompanying insulin resistance (IR) is an independent risk factor for stroke. The objective is to examine the cerebrovascular actions of insulin in Zucker obese (ZO) rats with IR and Zucker lean (ZL) control rats. Diameter measurements of cerebral arteries showed diminished insulin-induced vasodilation in ZO compared with ZL. Endothelial denudation revealed vasoconstriction to insulin that was greater in ZO compared with ZL. Nonspecific inhibition of nitric oxide synthase (NOS) paradoxically improved vasodilation in ZO. Scavenging of reactive oxygen species (ROS), supplementation of tetrahydrobiopterin (BH(4)) precursor, and inhibition of neuronal NOS or NADPH oxidase or cyclooxygenase (COX) improved insulin-induced vasodilation in ZO. Immunoblot experiments revealed that insulin-induced phosphorylation of Akt, endothelial NOS, and expression of GTP cyclohydrolase-I (GTP-CH) were diminished, but phosphorylation of PKC and ERK was enhanced in ZO arteries. Fluorescence studies showed increased ROS in ZO arteries in response to insulin that was sensitive to NOS inhibition and BH(4) supplementation. Thus, a vicious cycle of abnormal insulin-induced ROS generation instigating NOS uncoupling leading to further ROS production underlies the cerebrovascular IR in ZO rats. In addition, decreased bioavailability and impaired synthesis of BH(4) by GTP-CH induced by insulin promoted NOS uncoupling.

  14. 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

  15. [Epidemiology of obesity].

    PubMed

    Möhr, M

    1977-05-15

    In the GDR about 20% of the males and 40% of the females were estimated to be obese. In the country obesity is more spread than in the town. Increased disablement of obese persons leads to reduction of the national income. With higher expenses for nutrition the frequency of obestiy increases. Hypophages and hyperphages are differently distributed in persons with normal weight and obese ones, so that the average establishments do not reflect the differentiated situation in nutrition. Obesity correlates with the type of structure; with increasing obesity dominate pyknomorphous tendencies of growth. Also in normal weight pyknomorphous persons have a higher proportion of fat. We should speak of obesity in such a case, when, taking into consideration biological differentiations, the normal proportion of the fat in the body is increased by more than 1/3. For epidemiological serial examinations the degrees of relative weight basing on optimum weight are a favourable basis for the classification of obesity.

  16. Endocrine system and obesity.

    PubMed

    Ashburn, Doyle D; Reed, Mary Jane

    2010-10-01

    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients.

  17. Obesity Hypoventilation Syndrome

    MedlinePlus

    ... Twitter. What Is Obesity Hypoventilation Syndrome? Obesity hypoventilation (HI-po-ven-tih-LA-shun) syndrome (OHS) is ... e-DE-mah), pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), cor pulmonale (pul-meh-NAL- ...

  18. Reducing Childhood Obesity

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... page please turn Javascript on. The We Can! childhood obesity-prevention program involves parents, caregivers, and community leaders ...

  19. Overweight and Obesity Statistics

    MedlinePlus

    ... 6 percent were considered extremely obesese. Source: Ogden & Carroll, 2010; Flegal et al., 2012 **Data for 1960– ... clinical-guidelines-obesity-adults-evidence-report Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity ...

  20. Obesity and Anesthesia

    MedlinePlus

    ... Apnea and Anesthesia Smoking and Anesthesia Outpatient Surgery Obesity and Anesthesia More than one-third of Americans ... Sleep Apnea, a chronic medical problem common with obesity, can present with serious breathing problems before, during, ...

  1. Obesity and health (image)

    MedlinePlus

    Obesity increases a person's risk of illness and death due to diabetes, stroke, heart disease, hypertension, high cholesterol, and kidney and gallbladder disease. Obesity may increase the risk for some types of ...

  2. Obesity hypoventilation syndrome (OHS)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000085.htm Obesity hypoventilation syndrome (OHS) To use the sharing features on this page, please enable JavaScript. Obesity hypoventilation syndrome (OHS) is a condition in some ...

  3. Dietary combination of sucrose and linoleic acid causes skeletal muscle metabolic abnormalities in Zucker fatty rats through specific modification of fatty acid composition

    PubMed Central

    Ohminami, Hirokazu; Amo, Kikuko; Taketani, Yutaka; Sato, Kazusa; Fukaya, Makiko; Uebanso, Takashi; Arai, Hidekazu; Koganei, Megumi; Sasaki, Hajime; Yamanaka-Okumura, Hisami; Yamamoto, Hironori; Takeda, Eiji

    2014-01-01

    A dietary combination of sucrose and linoleic acid strongly contributes to the development of metabolic disorders in Zucker fatty rats. However, the underlying mechanisms of the metabolic disorders are poorly understood. We hypothesized that the metabolic disorders were triggered at a stage earlier than the 8 weeks we had previously reported. In this study, we investigated early molecular events induced by the sucrose and linoleic acid diet in Zucker fatty rats by comparison with other combinations of carbohydrate (sucrose or palatinose) and fat (linoleic acid or oleic acid). Skeletal muscle arachidonic acid levels were significantly increased in the sucrose and linoleic acid group compared to the other dietary groups at 4 weeks, while there were no obvious differences in the metabolic phenotype between the groups. Expression of genes related to arachidonic acid synthesis was induced in skeletal muscle but not in liver and adipose tissue in sucrose and linoleic acid group rats. In addition, the sucrose and linoleic acid group exhibited a rapid induction in endoplasmic reticulum stress and abnormal lipid metabolism in skeletal muscle. We concluded that the dietary combination of sucrose and linoleic acid primarily induces metabolic disorders in skeletal muscle through increases in arachidonic acid and endoplasmic reticulum stress, in advance of systemic metabolic disorders. PMID:25147427

  4. 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…

  5. The Complexity of Obesity

    ERIC Educational Resources Information Center

    Gray, Katti

    2010-01-01

    With Americans fatter and more malnourished than ever--almost two-thirds of the population is considered overweight or obese compared with 56 percent in the late 1980s and early 1990s, and people of color and the poor are the most obese of all--federal and university researchers and outreach workers from various anti-obesity organizations aim to…

  6. Childhood environment and obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    US children are at risk for developing childhood obesity. Currently, 23% of children ages 2–5 are overweight or obese, i.e., at or above the 85th percentile. This prevalence becomes even higher as children age, with 34% of children ages 6–11 being overweight or obese. Ethnic minority children are at...

  7. Childhood Obesity: An Overview

    ERIC Educational Resources Information Center

    Reilly, John J.

    2007-01-01

    This article reviews recent research evidence, largely from systematic reviews, on a number of aspects of childhood obesity: its definition and prevalence; consequences; causes and prevention. The basis of the body mass index (BMI) as a means of defining obesity in children and adolescents is discussed: a high BMI for age constitutes obesity. In…

  8. A Rosemary Extract Rich in Carnosic Acid Selectively Modulates Caecum Microbiota and Inhibits β-Glucosidase Activity, Altering Fiber and Short Chain Fatty Acids Fecal Excretion in Lean and Obese Female Rats

    PubMed Central

    Larrosa, Mar; Obiol, María; García-Villalba, Rocío; González-Barrio, Rocío; Issaly, Nicolas; Flanagan, John; Roller, Marc; Tomás-Barberán, Francisco A.; García-Conesa, María-Teresa

    2014-01-01

    Background Carnosic acid (CA) and rosemary extracts (RE) show body-weight, energy metabolism and inflammation regulatory properties in animal models but the mechanisms are not yet understood. Gut microbiota plays an important role in the host metabolism and inflammatory status and is modulated by the diet. The aim of this research was to investigate whether a RE enriched in CA affected caecum microbiota composition and activity in a rat model of genetic obesity. Methods and Principal Findings A RE (40% CA) was administered with the diet (0.5% w/w) to lean (fa/+) and obese (fa/fa) female Zucker rats for 64 days. Changes in the microbiota composition and β-glucosidase activity in the caecum and in the levels of macronutrients and short chain fatty acids (SCFA) in feces were examined. The RE increased the Blautia coccoides and Bacteroides/Prevotella groups and reduced the Lactobacillus/Leuconostoc/Pediococccus group in both types of animals. Clostridium leptum was significantly decreased and Bifidobacterium increased only in the lean rats. β-Glucosidase activity was significantly reduced and fecal fiber excretion increased in the two genotypes. The RE also increased the main SCFA excreted in the feces of the obese rats but decreased them in the lean rats reflecting important differences in the uptake and metabolism of these molecules between the two genotypes. Conclusions Our results indicate that the consumption of a RE enriched in CA modifies microbiota composition and decreases β-glucosidase activity in the caecum of female Zucker rats while it increases fiber fecal elimination. These results may contribute to explain the body weight gain reducing effects of the RE. The mutated leptin receptor of the obese animals significantly affects the microbiota composition, the SCFA fecal excretion and the host response to the RE intake. PMID:24733124

  9. 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.

  10. 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.

  11. Obesity and hypertension

    PubMed Central

    Jiang, Shu-Zhong; Lu, Wen; Zong, Xue-Feng; Ruan, Hong-Yun; Liu, Yi

    2016-01-01

    The imbalance between energy intake and expenditure is the main cause of excessive overweight and obesity. Technically, obesity is defined as the abnormal accumulation of ≥20% of body fat, over the individual's ideal body weight. The latter constitutes the maximal healthful value for an individual that is calculated based chiefly on the height, age, build and degree of muscular development. However, obesity is diagnosed by measuring the weight in relation to the height of an individual, thereby determining or calculating the body mass index. The National Institutes of Health have defined 30 kg/m2 as the limit over which an individual is qualified as obese. Accordingly, the prevalence of obesity in on the increase in children and adults worldwide, despite World Health Organization warnings. The growth of obesity and the scale of associated health issues induce serious consequences for individuals and governmental health systems. Excessive overweight remains among the most neglected public health issues worldwide, while obesity is associated with increasing risks of disability, illness and death. Cardiovascular diseases, the leading cause of mortality worldwide, particularly hypertension and diabetes, are the main illnesses associated with obesity. Nevertheless, the mechanisms underlying obesity-associated hypertension or other associated metabolic diseases remains to be adequately investigated. In the present review, we addressed the association between obesity and cardiovascular disease, particularly the biological mechanisms linking obesity and hypertension. PMID:27703502

  12. Obesity and ARDS

    PubMed Central

    Rice, Mary; Malhotra, Atul

    2012-01-01

    Obesity prevalence continues to increase globally, with figures exceeding 30% of some populations. Patients who are obese experience alterations in baseline pulmonary mechanics, including airflow obstruction, decreased lung volumes, and impaired gas exchange. These physiologic changes have implications in many diseases, including ARDS. The unique physiology of patients who are obese affects the presentation and pathophysiology of ARDS, and patients who are obese who have respiratory failure present specific management challenges. Although more study is forthcoming, ventilator strategies that focus on transpulmonary pressure as a measure of lung stress show promise in pilot studies. Given the increasing prevalence of obesity and the variable effects of obesity on respiratory mechanics and ARDS pathophysiology, we recommend an individualized approach to the management of the obese patient with ARDS. PMID:22948584

  13. Treatment for morbid obesity

    PubMed Central

    Carmichael, A

    1999-01-01

    There is no single unifying theory to explain the aetiology of obesity but several environmental factors, such as decreased physical activity and increased fat intake may contribute to its development in genetically predisposed individuals. Dietary and pharmacological treatments of morbid obesity have been proven to be unsuccessful. Modern surgical treatments have been shown to be effective in achieving significant weight loss with consequent reduction in morbidity. Despite the fact that surgical treatment of morbid obesity is the only therapeutic form that has stood the test of time, it still remains a crisis-driven form of therapy in the UK. It is probable that a better understanding of the aetiology and physiology of obesity may lead to the development of an effective pharmacological treatment of obesity in the future. However, until then, surgical treatment of morbid obesity should be considered as an effective and efficient way of treatment in selected cases.


Keywords: obesity PMID:10396579

  14. Obesity, Asthma, and the Microbiome

    PubMed Central

    Cho, Youngji

    2016-01-01

    Obesity is a risk factor for asthma, but standard asthma drugs have reduced efficacy in the obese. Obesity alters the gastrointestinal microbial community structure. This change in structure contributes to some obesity-related conditions and also could be contributing to obesity-related asthma. Although currently unexplored, obesity may also be altering lung microbiota. Understanding the role of microbiota in obesity-related asthma could lead to novel treatments for these patients. PMID:26889016

  15. Yacon diet (Smallanthus sonchifolius, Asteraceae) improves hepatic insulin resistance via reducing Trb3 expression in Zucker fa/fa rats

    PubMed Central

    Satoh, H; Audrey Nguyen, M T; Kudoh, A; Watanabe, T

    2013-01-01

    Objective: Yacon is a perennial plant forming a clump of >20 big, edible underground tubers. Yacon, which originates from South America, has become increasingly popular in the Japanese diet for tubers have a lower caloric value and a high fiber content. Recent studies have suggested that yacon feeding ameliorates diabetes as indicated by reduced blood glucose. Methods: We fed male Zucker fa/fa rats for 5 weeks with isocaloric normal chow diet containing from 6.5% control aroid or 6.5% yacon. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp study. Results: Body weight was comparable between yacon- and aroid-fed rats. In the basal state, yacon feeding had an effect to lower fasting glucose levels from 184.1±4.1 to 167.8±2.7 mg dl−1 (P<0.01), as well as basal hepatic glucose output (HGO) from 9.9±0.4 to 7.4 ± 0.2 mg kg−1 per min (P<0.01). During the clamp studies, the glucose infusion rate required to maintain euglycemia was increased by 12.3% in yacon-fed rat. The insulin suppression of HGO was also increased in yacon-fed rats compared with control rats (85.3±2.4% vs 77.0±3.0% P<0.05), whereas the glucose disposal rate was not different between the two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle. Furthermore, tribbles 3 (Trb3) expression, which is a negative regulator of Akt activity, was markedly reduced in the liver of yacon-fed rats compared with control rats. Conclusion: These results indicate that the effect of yacon feeding to reduce blood glucose is likely due to its beneficial effects on hepatic insulin sensitivity in the insulin resistant state. PMID:23712282

  16. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men.

    PubMed

    Berge, Kjetil; Piscitelli, Fabiana; Hoem, Nils; Silvestri, Cristoforo; Meyer, Ingo; Banni, Sebastiano; Di Marzo, Vincenzo

    2013-05-27

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m², age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome.

  17. Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models

    PubMed Central

    Rajpal, Deepak K.; Klein, Jean-Louis; Mayhew, David; Boucheron, Joyce; Spivak, Aaron T.; Kumar, Vinod; Ingraham, Karen; Paulik, Mark; Chen, Lihong; Van Horn, Stephanie; Thomas, Elizabeth; Sathe, Ganesh; Livi, George P.; Holmes, David J.; Brown, James R.

    2015-01-01

    The gastrointestinal tract microbiome has been suggested as a potential therapeutic target for metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). However, the relationship between changes in microbial communities and metabolic disease-phenotypes are still poorly understood. In this study, we used antibiotics with markedly different antibacterial spectra to modulate the gut microbiome in a diet-induced obesity mouse model and then measured relevant biochemical, hormonal and phenotypic biomarkers of obesity and T2DM. Mice fed a high-fat diet were treated with either ceftazidime (a primarily anti-Gram negative bacteria antibiotic) or vancomycin (mainly anti-Gram positive bacteria activity) in an escalating three-dose regimen. We also dosed animals with a well-known prebiotic weight-loss supplement, 10% oligofructose saccharide (10% OFS). Vancomycin treated mice showed little weight change and no improvement in glycemic control while ceftazidime and 10% OFS treatments induced significant weight loss. However, only ceftazidime showed significant, dose dependent improvement in key metabolic variables including glucose, insulin, protein tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Subsequently, we confirmed the positive hyperglycemic control effects of ceftazidime in the Zucker diabetic fatty (ZDF) rat model. Metagenomic DNA sequencing of bacterial 16S rRNA gene regions V1-V3 showed that the microbiomes of ceftazidime dosed mice and rats were enriched for the phylum Firmicutes while 10% OFS treated mice had a greater abundance of Bacteroidetes. We show that specific changes in microbial community composition are associated with obesity and glycemic control phenotypes. More broadly, our study suggests that in vivo modulation of the microbiome warrants further investigation as a potential therapeutic strategy for metabolic diseases. PMID:26709835

  18. Obesity and respiratory diseases.

    PubMed

    Zammit, Christopher; Liddicoat, Helen; Moonsie, Ian; Makker, Himender

    2010-10-20

    The obesity epidemic is a global problem, which is set to increase over time. However, the effects of obesity on the respiratory system are often underappreciated. In this review, we will discuss the mechanical effects of obesity on lung physiology and the function of adipose tissue as an endocrine organ producing systemic inflammation and effecting central respiratory control. Obesity plays a key role in the development of obstructive sleep apnea and obesity hypoventilation syndrome. Asthma is more common and often harder to treat in the obese population, and in this study, we review the effects of obesity on airway inflammation and respiratory mechanics. We also discuss the compounding effects of obesity on chronic obstructive pulmonary disease (COPD) and the paradoxical interaction of body mass index and COPD severity. Many practical challenges exist in caring for obese patients, and we highlight the complications faced by patients undergoing surgical procedures, especially given the increased use of bariatric surgery. Ultimately, a greater understanding of the effects of obesity on the respiratory disease and the provision of adequate health care resources is vital in order to care for this increasingly important patient population.

  19. Obesity and respiratory diseases

    PubMed Central

    Zammit, Christopher; Liddicoat, Helen; Moonsie, Ian; Makker, Himender

    2010-01-01

    The obesity epidemic is a global problem, which is set to increase over time. However, the effects of obesity on the respiratory system are often underappreciated. In this review, we will discuss the mechanical effects of obesity on lung physiology and the function of adipose tissue as an endocrine organ producing systemic inflammation and effecting central respiratory control. Obesity plays a key role in the development of obstructive sleep apnea and obesity hypoventilation syndrome. Asthma is more common and often harder to treat in the obese population, and in this study, we review the effects of obesity on airway inflammation and respiratory mechanics. We also discuss the compounding effects of obesity on chronic obstructive pulmonary disease (COPD) and the paradoxical interaction of body mass index and COPD severity. Many practical challenges exist in caring for obese patients, and we highlight the complications faced by patients undergoing surgical procedures, especially given the increased use of bariatric surgery. Ultimately, a greater understanding of the effects of obesity on the respiratory disease and the provision of adequate health care resources is vital in order to care for this increasingly important patient population. PMID:21116339

  20. Diffusing obesity myths.

    PubMed

    Ramos Salas, X; Forhan, M; Sharma, A M

    2014-06-01

    Misinformation or myths about obesity can lead to weight bias and obesity stigma. Counteracting myths with facts and evidence has been shown to be effective educational tools to increase an individuals' knowledge about a certain condition and to reduce stigma.The purpose of this study was to identify common obesity myths within the healthcare and public domains and to develop evidence-based counterarguments to diffuse them. An online search of grey literature, media and public health information sources was conducted to identify common obesity myths. A list of 10 obesity myths was developed and reviewed by obesity experts and key opinion leaders. Counterarguments were developed using current research evidence and validated by obesity experts. A survey of obesity experts and health professionals was conducted to determine the usability and potential effectiveness of the myth-fact messages to reduce weight bias. A total of 754 individuals responded to the request to complete the survey. Of those who responded, 464 (61.5%) completed the survey. All 10 obesity myths were identified to be deeply pervasive within Canadian healthcare and public domains. Although the myth-fact messages were endorsed, respondents also indicated that they would likely not be sufficient to reduce weight bias. Diffusing deeply pervasive obesity myths will require multilevel approaches.

  1. Pediatric obesity. An introduction.

    PubMed

    Yanovski, Jack A

    2015-10-01

    The prevalence of child and adolescent obesity in the United States increased dramatically between 1970 and 2000, and there are few indications that the rates of childhood obesity are decreasing. Obesity is associated with myriad medical, psychological, and neurocognitive abnormalities that impact children's health and quality of life. Genotypic variation is important in determining the susceptibility of individual children to undue gains in adiposity; however, the rapid increase in pediatric obesity prevalence suggests that changes to children's environments and/or to their learned behaviors may dramatically affect body weight regulation. This paper presents an overview of the epidemiology, consequences, and etiopathogenesis of pediatric obesity, serving as a general introduction to the subsequent papers in this Special Issue that address aspects of childhood obesity and cognition in detail.

  2. Obesity and kidney transplantation.

    PubMed

    Jindal, Rahul M; Zawada, Edward T

    2004-06-01

    There is a worldwide epidemic of obesity, and an increasing number of patients who are obese are presenting for solid-organ transplantation. Obesity increases the risk for delayed graft function and local wound complications after technically successful kidney transplantation. Obese patients are more likely to have comorbid factors leading to premature death with a functioning kidney transplant. We suggest the use of World Health Organization criteria when reporting the impact of obesity on recipients of solid-organ transplants. Prospective multicenter studies are indicated to evaluate long-term outcomes in obese patients who successfully receive a kidney transplant. Rigorous efforts should be made to optimize weight before and after solid-organ transplantation by a judicious combination of diet, exercise, minimization of steroid therapy, surgery, and psychological therapies.

  3. Obesity in pregnancy.

    PubMed

    Lim, Chu Chin; Mahmood, Tahir

    2015-04-01

    The prevalence of obesity has reached alarming proportions globally, and continues to rise in both developed and developing countries. Maternal obesity has become one of the most commonly occurring risk factors in obstetric practice. The 2003-2005 report of the Confidential Enquiries into Maternal Deaths in the United Kingdom highlighted obesity as a significant risk for maternal death [1]. More than half of all women who died from direct or indirect causes were either overweight or obese. For the mother, obesity increases the risk of obstetric complications during the antenatal, intrapartum and postnatal period, as well as contributing to technical difficulties with fetal assessment. The offspring of obese mothers also have a higher rate of perinatal morbidity and an increased risk of long-term health problems.

  4. Obesity: the worldwide epidemic.

    PubMed

    James, Philip T

    2004-01-01

    Over the last decade, the prevalence of obesity in Western and Westernizing countries has more than doubled. A standardized classification of overweight and obesity, based on the body mass index now allows a comparison of prevalence rates worldwide for the first time. In children, the International Obesity Taskforce age, sex, and BMI specific cut-off points are increasingly being used. BMI data are being evaluated as part of a new analysis of the Global Burden of Disease. Prevalence rates for overweight and obese people are very different in each region with the Middle East, Central and Eastern Europe and North American having higher prevalence rates. Obesity is usually now associated with poverty even in developing countries. Relatively new data suggest that abdominal obesity in adults, with its associated enhanced morbidity, occurs particularly in those who had lower birth weights and early childhood stunting.

  5. Female obesity and infertility.

    PubMed

    Talmor, Alon; Dunphy, Bruce

    2015-05-01

    Infertility affects one in seven couples, and its rate is on the increase. Ovulatory defects and unexplained causes account for >50% of infertile aetiologies. It is postulated that a significant proportion of these cases are either directly or indirectly related to obesity. The prevalence of overweight and obese men and women has topped 50% in some developed countries. Obesity is on the increase worldwide; in turn, the consequences in terms of the associated morbidity and mortality have also been increasing. Obesity is associated with various reproductive sequelae including anovulation, subfertility and infertility, increased risk of miscarriage and poor neonatal and maternal pregnancy outcomes. Thus, the combination of infertility and obesity poses some very real challenges in terms of both the short- and long-term management of these patients. The mechanism with which obesity impacts female reproductive function is summarised in this review.

  6. [Skin diseases and obesity].

    PubMed

    Guerra-Segovia, Carolina; Ocampo-Candiani, Jorge

    2015-01-01

    Obesity is a public health problem worldwide. It predominates in industrialized countries; however, it is prevalent in all nations. It is defined as a condition of excess adipose tissue and is the result of changes in lifestyle, excessive consumption of energy-dense foods with poor nutritional value, physical inactivity and the reduction of open space where one can practice a sport. Although obesity is associated with multiple diseases, it is important to stress that the metabolic changes caused by it affect skin physiology and play a predisposing factor for the development of skin diseases. Very little has been studied on the impact of obesity on the skin. The purpose of this article is to review the most frequently skin diseases in obesity. Some skin pathologies in obesity are caused by changes in skin physiology, others are related to insulin resistance or constitute an exacerbating factor for dermatitis. This article covers the clinical features of obesity related skin disease and its management.

  7. Citrus medica L. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress.

    PubMed

    Menichini, Francesco; Tundis, Rosa; Loizzo, Monica R; Bonesi, Marco; D'Angelo, Danila; Lombardi, Pietro; Mastellone, Vincenzo

    2016-12-01

    This study aimed to investigate the antidiabetic, antilipidaemic and antioxidant activities of Citrus medica cv Diamante (Rutaceae) hydroalcoholic (CD) peel extract in Zucker diabetic fatty (ZDF) rats. The ability of CD to protect against oxidative stress was investigated by using different in vitro assays and in vivo by using the reactive oxygen metabolites-derived compounds (d-ROMs) test and the biological antioxidant potential test (BAP). Two different doses of CD extract (300 and 600 mg/kg/die) were administered at ZDF rats for 4 weeks. CD reduced cholesterol and triglycerides levels. A dose-dependent effect on body weight and serum glucose levels was observed. A decrease of d-ROMs and an increase of BAP were recorded by using the dose of 600 mg/kg. The extract inhibited lipid peroxidation (IC50 value of 0.23 mg/ml). These findings suggest as an efficient phytotherapeutic approach in combating hyperlipidaemic and hyperglycaemic disorders.

  8. Virtual screening against obesity.

    PubMed

    Markt, P; Herdlinger, S; Schuster, D

    2011-01-01

    The development of novel drugs against obesity is one of the top priorities of worldwide drug research. In recent years, it has been facilitated by the application of virtual screening methods. In this review, we give a short introduction into obesity-related protein targets and computer-aided drug design techniques. Furthermore, we highlight the most successful virtual screening studies, outline their results, and provide suggestions for future anti-obesity drug development.

  9. 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

    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

  10. The economics of obesity.

    PubMed

    Finkelstein, Eric A; Strombotne, Kiersten L

    2010-05-01

    The rise in obesity rates, both nationally and internationally, is a result of changes in the environment that have simultaneously lowered the cost of food production, lowered the time and monetary cost of food consumption, increased the real cost of being physically active at work and at home, and decreased the health consequences that result from obesity by bringing a host of new drugs and devices to the market to better manage the adverse health effects that obesity promotes. This changing environment is in response to consumers' demand for labor-saving technology and convenient, affordable food. To be successful, efforts to combat obesity therefore need to recognize and address these realities.

  11. [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.

  12. Obesity and cholangiocarcinoma

    PubMed Central

    Parsi, Mansour A

    2013-01-01

    It is estimated that about half of the population in developed countries are either overweight or obese. In some developing nations obesity rates have increased to surpass those seen in Western countries. This rate increase in obesity has many implications as obesity has been associated with numerous negative health effects including increased risks of hypertension, diabetes, cardiovascular disease, stroke, liver disease, apnea, and some cancer types. Obesity is now considered to be one of the major public health concerns facing the society. Cholangiocarcinomas (bile duct cancers) are malignant tumors arising from cholangiocytes inside or outside of the liver. Although cholangiocarcinomas are relatively rare, they are highly lethal. The low survival rate associated with cholangiocarcinoma is due to the advanced stage of the disease at the time of diagnosis. Prevention is therefore especially important in this cancer type. Some data suggest that the incidence of cholangiocarcinoma in the western world is on the rise. Increasing rate of obesity may be one of the factors responsible for this increase. Determining whether obesity is a risk factor for cholangiocarcinoma has significant clinical and societal implications as obesity is both prevalent and modifiable. This paper seeks to provide a summary of the current knowledge linking obesity and cholangiocarcinoma, and encourage further research on this topic. PMID:23382624

  13. Economic Impact of Obesity.

    PubMed

    Spieker, Elena A; Pyzocha, Natasha

    2016-03-01

    Parallel to rising obesity rates is an increase in costs associated with excess weight. Estimates of future direct (medical) and indirect (nonmedical) costs related to obesity suggest rising expenditures that will impose a significant economic burden to individuals and society as a whole. This article reviews research on direct and indirect medical costs and future economic trends associated with obesity and associated comorbidities. Cost disparities associated with subsets of the population experiencing higher than average rates of obesity are explored. Finally, potential solutions with the highest estimated impact are offered, and future directions are proposed.

  14. [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.

  15. DBS for Obesity

    PubMed Central

    Franco, Ruth; Fonoff, Erich T.; Alvarenga, Pedro; Lopes, Antonio Carlos; Miguel, Euripides C.; Teixeira, Manoel J.; Damiani, Durval; Hamani, Clement

    2016-01-01

    Obesity is a chronic, progressive and prevalent disorder. Morbid obesity, in particular, is associated with numerous comorbidities and early mortality. In patients with morbid obesity, pharmacological and behavioral approaches often have limited results. Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects. In the last decades, deep brain stimulation (DBS) has been investigated as a neurosurgical modality to treat various neuropsychiatric disorders. In this article we review the rationale for selecting different brain targets, surgical results and future perspectives for the use of DBS in medically refractory obesity. PMID:27438859

  16. 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

  17. Obesity in Infants to Preschoolers

    MedlinePlus

    ... a Healthy Heart Healthy Kids Our Kids Programs Childhood Obesity What is childhood obesity? Overweight in Children BMI in Children Is Childhood Obesity an Issue in Your Home? Addressing your Child's ...

  18. What Are Overweight and Obesity?

    MedlinePlus

    ... page from the NHLBI on Twitter. Overweight and Obesity Español Also known as adiposity. Overweight and obesity ... more information. Rate This Content: NEXT >> Featured Video Obesity happens one pound at a time. So does ...

  19. Identification and Verification of Potential Therapeutic Target Genes in Berberine-Treated Zucker Diabetic Fatty Rats through Bioinformatics Analysis

    PubMed Central

    Bao, Yu-Ting; Li, Zhe-Ming; Zhou, Xiao-Jie; He, Jia-Na; Dai, Shi-Jie; Li, Chang yu

    2016-01-01

    Background Berberine is used to treat diabetes and dyslipidemia. However, the effect of berberine on specific diabetes treatment targets is unknown. In the current study, we investigated the effect of berberine on the random plasma glucose, glycated hemoglobin (HbA1C), AST, ALT, BUN and CREA levels of Zucker diabetic fatty (ZDF) rats, and we identified and verified the importance of potential therapeutic target genes to provide molecular information for further investigation of the mechanisms underlying the anti-diabetic effects of berberine. Methods ZDF rats were randomly divided into control (Con), diabetic (DM) and berberine-treated (300 mg⋅kg−1, BBR) groups. After the ZDF rats were treated with BBR for 12 weeks, its effect on the random plasma glucose and HbA1C levels was evaluated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), CREA and OGTT were measured from blood, respectively. The levels of gene expression in liver samples were analyzed using an Agilent rat gene expression 4x44K microarray. The differentially expressed genes (DEGs) were screened as those with log2 (Con vs DM) ≥ 1 and log2 (BBR vs DM) ≥ 1 expression levels, which were the genes with up-regulated expression, and those with log2 (Con vs DM) ≤ -1 and log2 (BBR vs DM) ≤ -1 expression levels, which were the genes with down-regulated expression; the changes in gene expression were considered significant at P<0.05. The functions of the DEGs were determined using gene ontology (GO) and pathway analysis. Furthermore, a protein-protein interaction (PPI) network was constructed using STRING and Cytoscape software. The expression levels of the key node genes in the livers of the ZDF rats were also analyzed using qRT-PCR. Results We found that 12 weeks of berberine treatment significantly decreased the random plasma glucose, HbA1C levels and improved glucose tolerance. There was a tendency for berberine to reduce AST, ALT, BUN except increase

  20. 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.

  1. Gender, Obesity, and Education

    ERIC Educational Resources Information Center

    Crosnoe, Robert

    2007-01-01

    Obesity is a health condition, but its consequences extend far beyond the realm of health. To illuminate an important route by which the experience of obesity can filter into the status attainment process, this study drew on nationally representative data from the National Longitudinal Study of Adolescent Health to test a social psychological…

  2. Battling the Obesity Epidemic.

    ERIC Educational Resources Information Center

    Kelly, Mark; Moag-Stahlberg, Alicia

    2002-01-01

    Describes causes of overweight and obesity in children; cites research linking good nutrition and a child's capacity to learn; includes six Web-based links to resources to help principals and teachers reduce the serious problem of overweight and obese children. (PKP)

  3. How Bad Is Obesity?

    ERIC Educational Resources Information Center

    Schroeder, Ken

    2006-01-01

    A University of California at Los Angeles study in the Journal of Health Politics, Policy and Law suggests that the proportion of obese Americans has risen 20% since 1980, but the so-called obesity epidemic is at best a metaphor and not a very effective one at that. However, recent research finds no appreciable difference in mortality rates among…

  4. Effective Obesity Treatments

    ERIC Educational Resources Information Center

    Powell, Lynda H.; Calvin, James E., III; Calvin, James E., Jr.

    2007-01-01

    To curb the epidemic of obesity in the United States, revised Medicare policy allows support for efficacious obesity treatments. This review summarizes the evidence from rigorous randomized trials (9 lifestyle trials, 5 drug trials, and 2 surgical trials) on the efficacy and risk-benefit profile of lifestyle, drug, and surgical interventions aimed…

  5. [Genetics of pediatric obesity].

    PubMed

    Peralta-Romero, José de Jesús; Gómez-Zamudio, Jaime Héctor; Estrada-Velasco, Bárbara; Karam-Araujo, Roberto; Cruz-López, Miguel

    2014-01-01

    Obesity is a major health problem around the globe. The statistics of overweight and obesity at early ages have reached alarming levels and placed our country in the first place in regard to childhood obesity. In the development of obesity two major factors take part, one genetic and the other one environmental. From the perspective of environmental changes both overweight and obesity result from the imbalance in the energy balance: people ingest more energy than they expend. Despite people live in the same obesogenic environment not all of them develop obesity; it requires genetic factors for this to happen. This review focuses on the description of the main methodologies to find genetic markers, as well as the main loci in candidate genes, whose single nucleotide polymorphisms (SNPs) are associated with obesity and its comorbidities in children, highlighting the association of these genes in the Mexican population. Knowledge of the genetic markers associated with obesity will help to understand the molecular and physiological mechanisms, the genetic background and changes in body mass index in the Mexican population. This information is useful for the planning of new hypotheses in the search for new biomarkers that can be used in a predictive and preventive way, as well as for the development of new therapeutic strategies.

  6. Childhood Obesity. ERIC Digest.

    ERIC Educational Resources Information Center

    Summerfield, Liane M.

    In this discussion of childhood obesity, the medical and psychological problems associated with the condition are noted. Childhood obesity most likely results from an interaction of nutritional, psychological, familial, and physiological factors. Three factors--the family, low-energy expenditure, and heredity--are briefly examined. Early…

  7. Obesity: A Bibliographic Review

    ERIC Educational Resources Information Center

    McGowan, Beth

    2012-01-01

    The study of obesity is a relatively new interdisciplinary academic field. The community college library shelves should contain two types of resources. First, several kinds of reference materials, and second, a host of broader materials that place the discussion of obesity within a cultural framework. This overview is divided into two major…

  8. Personalized nutrition and obesity.

    PubMed

    Qi, Lu

    2014-08-01

    The past few decades have witnessed a rapid rise in nutrition-related disorders such as obesity in the United States and over the world. Traditional nutrition research has associated various foods and nutrients with obesity. Recent advances in genomics have led to identification of the genetic variants determining body weight and related dietary factors such as intakes of energy and macronutrients. In addition, compelling evidence has lent support to interactions between genetic variations and dietary factors in relation to obesity and weight change. Moreover, recently emerging data from other 'omics' studies such as epigenomics and metabolomics suggest that more complex interplays between the global features of human body and dietary factors may exist at multiple tiers in affecting individuals' susceptibility to obesity; and a concept of 'personalized nutrition' has been proposed to integrate this novel knowledge with traditional nutrition research, with the hope ultimately to endorse person-centric diet intervention to mitigate obesity and related disorders.

  9. 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.

  10. Genetics of obesity.

    PubMed

    Clement, Karine; Boutin, Philippe; Froguel, Philippe

    2002-01-01

    Obesity is a typical common multifactorial disease in which environmental and genetic factors interact. In rare cases of severe obesity with childhood onset, a single gene has a major effect in determining the occurrence of obesity, with the environment having only a permissive role in the severity of the phenotype. Exceptional mutations of the leptin gene and its receptor, pro-opiomelanocortine (POMC), prohormone convertase 1 (PC1) and more frequently, mutations in the melanocortin receptor 4 (1 to 4% of very obese cases) have been described. All these obesity genes encode proteins that are strongly connected as part of the same loop of the regulation of food intake. They all involve the leptin axis and one of its hypothalamic targets; the melanocortin pathway. Pathways of bodyweight regulation involved in monogenic forms of obesity might represent targets for future drug development. Successful leptin protein replacement in a leptin-deficient child has contributed to the validation of the usefulness of gene screening in humans. However, the individual variability in response to leptin treatment might be related to genetic variability. The efficiency of leptin itself or of small-molecule agonists of the leptin receptor should be studied in relation with genetic variations in the leptin gene promoter. The most common forms of obesity are polygenic. Two general approaches have been used to date in the search for genes underlying common polygenic obesity in humans. The first approach focuses on selected genes having some plausible role in obesity on the basis of their known or presumed biological role. This approach yielded putative susceptibility genes with only small or uncertain effects. The second approach attempts to map genes purely by position and requires no presumptions on the function of genes. Genome-wide scans identify chromosomal regions showing linkage with obesity in large collections of nuclear families. Genome-wide scans in different ethnic

  11. 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.

  12. Obesity in children & adolescents.

    PubMed

    Raj, Manu; Kumar, R Krishna

    2010-11-01

    Worldwide, obesity trends are causing serious public health concern and in many countries threatening the viability of basic health care delivery. It is an independent risk factor for cardiovascular diseases and significantly increases the risk of morbidity and mortality. The last two decades have witnessed an increase in health care costs due to obesity and related issues among children and adolescents. Childhood obesity is a global phenomenon affecting all socio-economic groups, irrespective of age, sex or ethnicity. Aetiopathogenesis of childhood obesity is multi-factorial and includes genetic, neuroendocrine, metabolic, psychological, environmental and socio-cultural factors. Many co-morbid conditions like metabolic, cardiovascular, psychological, orthopaedic, neurological, hepatic, pulmonary and renal disorders are seen in association with childhood obesity. The treatment of overweight and obesity in children and adolescents requires a multidisciplinary, multi-phase approach, which includes dietary management, physical activity enhancement, restriction of sedentary behaviour, pharmacotherapy and bariatric surgery. A holistic approach to tackle the childhood obesity epidemic needs a collection of activities including influencing policy makers and legislation, mobilizing communities, restructuring organizational practices, establishing coalitions and networks, empowering providers, imparting community education as well as enriching and reinforcing individual awareness and skills. The implications of this global phenomenon on future generations will be serious unless appropriate action is taken.

  13. Obesity and Economic Environments

    PubMed Central

    Sturm, Roland; An, Ruopeng

    2014-01-01

    This review summarizes our understanding of economic factors during the obesity epidemic and dispels some widely held, but incorrect, beliefs: Rising obesity rates coincided with increases in leisure time (rather than increased work hours), increased fruit and vegetable availability (rather than a decline of healthier foods), and increased exercise uptake. As a share of disposable income, Americans now have the cheapest food available in history, which fueled the obesity epidemic. Weight gain was surprisingly similar across sociodemographic groups or geographic areas, rather than specific to some groups (at every point in time, however, there are clear disparities). It suggests that if we want to understand the role of the environment in the obesity epidemic, we need to understand changes over time affecting all groups, not differences between subgroups at a given time. Although economic and technological changes in the environment drove the obesity epidemic, the evidence for effective economic policies to prevent obesity remains limited. Taxes on foods with low nutritional value could nudge behavior towards healthier diets, as could subsidies/discounts for healthier foods. However, even a large price change for healthy foods could only close a part of the gap between dietary guidelines and actual food consumption. Political support has been lacking for even moderate price interventions in the US and this may continue until the role of environment factors is accepted more widely. As opinion leaders, clinicians play an important role to shape the understanding of the causes of obesity. PMID:24853237

  14. Beneficial Effects of Canagliflozin in Combination with Pioglitazone on Insulin Sensitivity in Rodent Models of Obese Type 2 Diabetes

    PubMed Central

    Watanabe, Yoshinori; Nakayama, Keiko; Taniuchi, Nobuhiko; Horai, Yasushi; Kuriyama, Chiaki; Ueta, Kiichiro; Arakawa, Kenji; Senbonmatsu, Takaaki; Shiotani, Masaharu

    2015-01-01

    Background Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. Methods Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. Results In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. Conclusions Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes. PMID:25615826

  15. Obesity and cancer.

    PubMed

    Pischon, Tobias; Nöthlings, Ute; Boeing, Heiner

    2008-05-01

    The prevalence of obesity, defined as a BMI of > or =30.0 kg/m2, has increased substantially over previous decades to about 20% in industrialized countries, and a further increase is expected in the future. Epidemiological studies have shown that obesity is a risk factor for: post-menopausal breast cancer; cancers of the endometrium, colon and kidney; malignant adenomas of the oesophagus. Obese subjects have an approximately 1.5-3.5-fold increased risk of developing these cancers compared with normal-weight subjects, and it has been estimated that between 15 and 45% of these cancers can be attributed to overweight (BMI 25.0-29.9 kg/m2) and obesity in Europe. More recent studies suggest that obesity may also increase the risk of other types of cancer, including pancreatic, hepatic and gallbladder cancer. The underlying mechanisms for the increased cancer risk as a result of obesity are unclear and may vary by cancer site and also depend on the distribution of body fat. Thus, abdominal obesity as defined by waist circumference or waist:hip ratio has been shown to be more strongly related to certain cancer types than obesity as defined by BMI. Possible mechanisms that relate obesity to cancer risk include insulin resistance and resultant chronic hyperinsulinaemia, increased production of insulin-like growth factors or increased bioavailability of steroid hormones. Recent research also suggests that adipose tissue-derived hormones and cytokines (adipokines), such as leptin, adiponectin and inflammatory markers, may reflect mechanisms linked to tumourigenesis.

  16. Obesity and the elderly.

    PubMed

    Mathus-Vliegen, Elisabeth M H

    2012-08-01

    The prevalence of obesity is rising progressively, even among older age groups. By the year 2030 to 2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years or older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The predicted prevalence of obesity in Europe in 2015 varies between 20% and 30% dependent on the model used. This means 20.9 million obese 60 years or older people in the United States in 2010 and 32 million obese elders in 2015 in EU. Although cutoff values of body mass index, waist circumference, and percentages of fat mass have not been defined for the elderly, it is clear from several meta-analyses that mortality and morbidity associated with overweight and obesity only increases at a body mass index >30 kg/m(2). Thus, treatment should only be offered to patients who are obese rather than overweight and who have functional impairments, metabolic complications, or obesity-related diseases, that can benefit from weight loss. The weight loss therapy should minimize muscle and bone loss and vigilance as regards the development of sarcopenic obesity--a combination of an unhealthy excess of body fat with a detrimental loss of muscle and fat-free mass including bone--is important. Lifestyle intervention should be the first step and consists of a diet with a 500 kcal energy deficit and an adequate intake of protein of high biological quality, together with calcium and vitamin D, behavioral therapy, and multicomponent exercise. Multicomponent exercise includes flexibility training, balance training, aerobic exercise, and resistance training. The adherence rate in most studies is around 75%. Knowledge of constraints and modulators of physical inactivity should be of help to engage the elderly in physical activity. The role of pharmacotherapy and bariatric surgery in the elderly is largely unknown as in most studies people aged 65 years and older were excluded.

  17. Reinforcement pathology and obesity.

    PubMed

    Carr, Katelyn A; Daniel, Tinuke Oluyomi; Lin, Henry; Epstein, Leonard H

    2011-09-01

    Obesity is, in part, a result of positive energy balance or energy intake exceeding physiological needs. Excess energy intake is determined by a series of food choices over time. These choices involve both motivational and executive function processes. Problems arise when there is excessive motivation to eat and low impulse control, a situation we have termed reinforcement pathology. Motivational and executive function processes have also been implicated in the development of drug dependence and addiction. In this review we discuss the application of reinforcement pathology to obesity, and implications of this approach for obesity treatment.

  18. Obesity and diabetes.

    PubMed

    Riobó Serván, Pilar

    2013-09-01

    Type 2 diabetes mellitus is characterized by hyperglycemia, insulin resistance, and relative impairment in insulin secretion and its possible long term complications. Its pathogenesis is poorly understood, but both genetic and environmental factors, such as obesity and aging, play a key role. "Diabesity" is a new term which refers to diabetes occurring in the context of obesity. In this article, we will discuss the epidemiology and impact of diabetes and obesity and will also outline the components of the metabolic syndrome and the studies that demonstrate that screening and prevention are possible in an attempt to control this epidemic.

  19. Obesity and cancer pathogenesis

    PubMed Central

    Berger, Nathan A.

    2015-01-01

    Overweight and obesity have reached pandemic levels on a worldwide basis and are associated with increased risk and worse prognosis for many but not all malignancies. Pathophysiologic processes that affect this association are reviewed, with a focus on the relation of type 2 diabetes mellitus with cancer, lessons learned from the use of murine models to study the association, the impact of obesity on pancreatic cancer, the effect of dietary fats and cholesterol as cancer promoters, and the mechanisms by which the intestinal microbiome affects obesity and cancer. PMID:24725147

  20. Obesity in women.

    PubMed

    Ryan, Donna H; Braverman-Panza, Jill

    2014-02-01

    Obesity is a common disorder affecting approximately 1 in 3 women. Assessment should consist of measuring BMI and waist circumference, a thorough history regarding nutrition, physical activity, and prior attempts at weight loss, and identification of obesity-related comorbidities. As a chronic disease, obesity requires management using a chronic care model employing multimodal therapy. Behavioral therapy to bring about changes in nutrition and physical activity can be supplemented with long-term use of medications (lorcaserin, orlistat, phentermine/topiramate) to help patients both achieve and maintain meaningful weight loss.

  1. Defining Overweight and Obesity

    MedlinePlus

    ... 2013. A comparison of the Slaughter skinfold-thickness equations and BMI in predicting body fatness and cardiovascular ... Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs File Formats Help: How do ...

  2. Obesity in gulf countries.

    PubMed

    ALNohair, Sultan

    2014-01-01

    Globally obesity has reached to epidemic proportions, and the people of the Gulf countries have also affected, especially high-income, oil-producing countries. The prevalence of obesity in Gulf Countries among children and adolescents ranges from 5% to 14% in males and from 3% to 18% in females. In adult females there is a significant increase of obesity with a prevalence of 2%-55% and in adult males 1%-30% in countries of gulf region. Over the last two decades there is increased consumption of fast foods and sugar-dense beverages (e.g., sodas). Simultaneously, technological advances - cars, elevators, escalators, and remotes have lead to a decrease in level of activity. Traditional dependence on locally grown natural products such as dates, vegetables, wheat and has also shifted. Changes in food consumption, socioeconomic and demographic factors, physical activity, and urbanization are being important factors that contribute to the increased prevalence of obesity in the region.

  3. Adipokines in childhood obesity.

    PubMed

    Martos-Moreno, Gabriel Ángel; Barrios, Vicente; Chowen, Julie A; Argente, Jesús

    2013-01-01

    The worldwide increase in the prevalence of obesity in children and adolescents during the past decades, in addition to mounting evidence indicating that obesity is associated with an increased incidence of comorbidities and the risk of premature death, resulting in a high economical impact, has stimulated obesity-focused research. These studies have highlightened the prominent endocrine activity of adipose tissue, which is exerted through the synthesis and secretion of a wide variety of peptides and cytokines, called adipokines. In the present review, we have summarized the current knowledge and most relevant studies of adipokine dynamics and actions in children, focusing on the control of energy homeostasis, metabolic regulation (particularly, carbohydrate metabolism), and inflammation. The particularities of adipose secretion and actions in healthy children, from birth to adolescence, and the modifications induced by early-onset obesity are highlighted.

  4. Worldwide epidemiology of obesity.

    PubMed

    VanItallie, T B

    1994-01-01

    Average body mass index values and prevalence data for overweight show complex patterns varying with sex, age, socioeconomic circumstances, race, geography, and over time. Differences in the predominant lifestyles and developmental status of nations and regions also influence weight patterns. Estimates of the prevalence of obesity in developed countries vary depending on the definitions used. For example, one recent survey has reported that the prevalence of obesity in the US is 15%, while another survey has found it to be 26%. It appears that overweight and obesity are becoming more prevalent worldwide, not only in developed nations, but also in the populations of developing countries, possibly as a result of urbanisation, migration, new eating habits and recent affluence. Since modernisation appears to be an inevitable process throughout the world, there is every reason to expect that the epidemic of overweight and obesity will extend globally in the future.

  5. Health risks of obesity

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000348.htm Health risks of obesity To use the sharing features on ... also have an increased risk of these conditions. Risk Factors Having a risk factor does not mean ...

  6. Disability and Obesity

    MedlinePlus

    ... of certain diseases and other health problems. Behavior, environment, and genetic factors can affect whether a person is overweight or obese. Healthy Weight Issue Briefs Download and print these issue ...

  7. Early determinants of obesity.

    PubMed

    Ong, Ken K

    2010-01-01

    High rates of overweight and obesity even in very young children argue the case for strategies to prevent overweight from very young ages. Historical studies, prospective birth cohorts, and more recently genetic studies all indicate that the rapid weight gain trajectory to later obesity starts in the first months of life, even from birth. Early puberty and age at menarche are consequences of rapid infant weight gain and childhood overweight, and in turn these adolescent traits are predictive for obesity, diabetes, hypertension and cardiovascular disease events in later life. Understanding of the nutritional, parental and wider determinants of rapid infant weight gain are informing the development of obesity prevention strategies starting in early life. Such strategies could be further refined by future studies that address the specific regulation of infant adiposity, and also by studies that explore whether these life-course trajectories are modifiable during adolescence.

  8. Childhood Obesity Facts

    MedlinePlus

    ... BMI-for-age growth charts . 1 Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity ... Center for Health Statistics. 2015. 2 Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, ...

  9. Homeostatic theory of obesity

    PubMed Central

    2015-01-01

    Health is regulated by homeostasis, a property of all living things. Homeostasis maintains equilibrium at set-points using feedback loops for optimum functioning of the organism. Imbalances in homeostasis causing overweight and obesity are evident in more than 1 billion people. In a new theory, homeostatic obesity imbalance is attributed to a hypothesized ‘Circle of Discontent’, a system of feedback loops linking weight gain, body dissatisfaction, negative affect and over-consumption. The Circle of Discontent theory is consistent with an extensive evidence base. A four-armed strategy to halt the obesity epidemic consists of (1) putting a stop to victim-blaming, stigma and discrimination; (2) devalorizing the thin-ideal; (3) reducing consumption of energy-dense, low-nutrient foods and drinks; and (4) improving access to plant-based diets. If fully implemented, interventions designed to restore homeostasis have the potential to halt the obesity epidemic. PMID:28070357

  10. Chronobiological Effects on Obesity.

    PubMed

    Bray, Molly S; Young, Martin E

    2012-03-01

    The development of obesity is the consequence of a multitude of complex interactions between both genetic and environmental factors. It has been suggested that the dramatic increase in the prevalence of obesity over the past 30 years has been the result of environmental changes that have enabled the full realization of genetic susceptibility present in the population. Among the many environmental alterations that have occurred in our recent history is the ever-increasing dyssynchrony between natural cycles of light/dark and altered patterns of sleep/wake and eating behavior associated with our "24-hour" lifestyle. An extensive research literature has established clear links between increased risk for obesity and both sleep deprivation and shift work, and our understanding of the consequences of such dyssynchrony at the molecular level is beginning to emerge. Studies linking alterations in cellular circadian clocks to metabolic dysfunction point to the increasing importance of chronobiology in obesity etiology.

  11. Homeostatic theory of obesity.

    PubMed

    Marks, David F

    2015-01-01

    Health is regulated by homeostasis, a property of all living things. Homeostasis maintains equilibrium at set-points using feedback loops for optimum functioning of the organism. Imbalances in homeostasis causing overweight and obesity are evident in more than 1 billion people. In a new theory, homeostatic obesity imbalance is attributed to a hypothesized 'Circle of Discontent', a system of feedback loops linking weight gain, body dissatisfaction, negative affect and over-consumption. The Circle of Discontent theory is consistent with an extensive evidence base. A four-armed strategy to halt the obesity epidemic consists of (1) putting a stop to victim-blaming, stigma and discrimination; (2) devalorizing the thin-ideal; (3) reducing consumption of energy-dense, low-nutrient foods and drinks; and (4) improving access to plant-based diets. If fully implemented, interventions designed to restore homeostasis have the potential to halt the obesity epidemic.

  12. Obesity in Gulf Countries

    PubMed Central

    ALNohair, Sultan

    2014-01-01

    Globally obesity has reached to epidemic proportions, and the people of the Gulf countries have also affected, especially high-income, oil-producing countries. The prevalence of obesity in Gulf Countries among children and adolescents ranges from 5% to 14% in males and from 3% to 18% in females. In adult females there is a significant increase of obesity with a prevalence of 2%–55% and in adult males 1%–30% in countries of gulf region. Over the last two decades there is increased consumption of fast foods and sugar-dense beverages (e.g., sodas). Simultaneously, technological advances – cars, elevators, escalators, and remotes have lead to a decrease in level of activity. Traditional dependence on locally grown natural products such as dates, vegetables, wheat and has also shifted. Changes in food consumption, socioeconomic and demographic factors, physical activity, and urbanization are being important factors that contribute to the increased prevalence of obesity in the region. PMID:24899882

  13. The prevalence of obesity.

    PubMed

    Wyatt, Holly R

    2003-06-01

    During the past several decades, obesity has increased substantially, making it a true epidemic and a public health crisis that both health care providers and the public are going to have to face. Currently, 61% of the US population is overweight or obese and therefore at increased risk for a number of diseases that are associated with increased body fat. Indeed, the obesity epidemic already is leading to dramatic increases in type 2 diabetes and the metabolic syndrome. Almost a quarter of the population currently has metabolic syndrome, which places them at high risk for the development of coronary heart disease. The future of the general health of the US population depends on identifying and providing the best treatment and prevention strategies for obesity in the years ahead.

  14. Obesity in children

    MedlinePlus

    ... Weight loss drugs are not recommended for children. Bariatric surgery is currently being performed for some children, but ... et al. Best practice updates for pediatric/adolescent weight loss surgery. Obesity (Silver Spring). 2009 May;17(5):901- ...

  15. Insulin-Regulated Srebp-1c and Pck1 mRNA Expression in Primary Hepatocytes from Zucker Fatty but Not Lean Rats Is Affected by Feeding Conditions

    PubMed Central

    Zhang, Yan; Chen, Wei; Li, Rui; Li, Yang; Ge, Yuebin; Chen, Guoxun

    2011-01-01

    Insulin regulates the transcription of genes for hepatic glucose and lipid metabolism. We hypothesized that this action may be impaired in hepatocytes from insulin resistant animals. Primary hepatocytes from insulin sensitive Zucker lean (ZL) and insulin resistant Zucker fatty (ZF) rats in ad libitum or after an overnight fasting were isolated, cultured and treated with insulin and other compounds for analysis of gene expression using real-time PCR. The mRNA levels of one insulin-induced (Srebp-1c) and one insulin-suppressed (Pck1) genes in response to insulin, glucagon, and compactin treatments in hepatocytes from ad libitum ZL and ZF rats were analyzed. Additionally, the effects of insulin and T1317 on their levels in hepatocytes from ad libitum or fasted ZL or ZF rats were compared. The mRNA levels of Srebp-1c, Fas, and Scd1, but not that of Insr, Gck and Pck1, were higher in freshly isolated hepatocytes from ad libitum ZF than that from ZL rats. These patterns of Srebp-1c and Pck1 mRNA levels remained in primary hepatocyte cultured in vitro. Insulin's ability to regulate Srebp-1c and Pck1 expression was diminished in hepatocytes from ad libitum ZF, but not ZL rats. Glucagon or compactin suppressed Srebp-1c mRNA expression in lean, but not fatty hepatocytes. However, glucagon induced Pck1 mRNA expression similarly in hepatocytes from ad libitum ZL and ZF rats. Insulin caused the same dose-dependent increase of Akt phosphorylation in hepatocytes from ad libitum ZL and ZF rats. It synergized with T1317 to induce Srebp-1c, and suppressed Pck1 mRNA levels in hepatocytes from fasted, but not that from ad libitum ZF rats. We demonstrated that insulin was unable to regulate its downstream genes' mRNA expression in hepatocytes from ad libitum ZF rats. This impairment can be partially restored in hepatocytes from ZF rats after an overnight fasting, a phenomenon that deserves further investigation. PMID:21731709

  16. Obesity: a growing problem.

    PubMed

    Seidell, J C

    1999-02-01

    Obesity, defined as a body mass index (BMI) of 30 kg/m2 or more, is common in many parts of the world, especially in the established market economies, the former socialist economies of Europe, Latin America, the Caribbean and the Middle Eastern Crescent. As many as 250 million people worldwide may be obese (7% of the adult population) and two to three times as many may be considered overweight. The prevalence of obesity seems to be increasing in most parts of the world, even where it used to be rare. Increased fatness, measured by a high BMI, a large waist circumference or a high waist/hip circumference ratio, is associated with many chronic diseases as well as with poor physical functioning. Assessments of the prevalence of obesity, and trends in this prevalence over time, are more difficult in children than adults, due to the lack of international criteria for classifying individuals as overweight or obese. The World Health Organization has now recommended the use of BMI-for-age percentiles, but the reference curves are still under development. France. The Netherlands, the UK and the USA are among the countries that have reported recent increases in the prevalence of obesity in children and adolescents. Although there are no accurate estimates of the components of energy balance and their changes over time, the available evidence suggests that the trends in obesity rates are related more to a reduction in energy expenditure than to an increase in caloric intake. Prevention of obesity through the promotion of a healthy lifestyle is among the important challenges for the new millennium, and should start in childhood.

  17. [Obesity and male fertility].

    PubMed

    Martini, Ana C; Molina, Rosa I; Ruiz, Rubén D; Fiol de Cuneo, Marta

    2012-01-01

    Obesity and male infertility have increased in the last decades; therefore, a possible association between these pathologies has been explored. Studies inform that obesity may affect fertility through different mechanisms, which alltogether could exert erectile dysfunction and/or sperm quality impairment. These include: 1) hypothalamic-pituitary-testicular (HPG) axis malfunction: obese hormonal profile is characterized by reduction of testosterone, gonadotrophins, SHBG and/or inhibin B concentrations (marker of Sertoli cells function) and hyperestrogenemy (consequence of aromatase overactivity ascribed to adipose tissue increase); 2) increased release of adipose-derived hormones: leptin increase could be responsible for some of the alterations on the HPG axis and could also exert direct deleterious effects on Leydig cells physiology, spermatogenesis and sperm function; 3) proinflammatory adipokines augmentation, higher scrotal temperature (due to fat accumulation in areas surrounding testes) and endocrine disruptors accumulation in adiposites, all of these responsible for the increase in testes oxidative stress and 4) sleep apnea, frequent in obese patients, suppresses the nocturnal testosterone rise needed for normal spermatogenesis. Finally, although controversial, all the above mentioned factors could comprise gametes quality; i.e. decrease sperm density and motility and increase DNA fragmentation, probably disturbing spermatogenesis and/or epididymal function. In summary, although obesity may impair male fertility by some/all of the described mechanisms, the fact is that only a small proportion of obese men are infertile, probably those genetically predisposed or morbidly obese. Nevertheless, it is likely that because the incidence of obesity is growing, the number of men with reduced fertility will increase as well.

  18. Preventing Obesity through Schools

    PubMed Central

    Nihiser, Allison; Merlo, Caitlin; Lee, Sarah

    2015-01-01

    PRÉCIS This paper describes highlights from the Weight of the Nation™ 2012 Schools Track. Included is a summary of 16 presentations. Presenters shared key actions for obesity prevention through schools. The information provided at the Weight of the Nation™ can help school health practitioners access tools, apply evidence-based strategies, and model real-world examples to successfully start obesity prevention initiatives in their jurisdiction. PMID:24446995

  19. Pharmacotherapy for obesity

    PubMed Central

    Li, Mingfang; Cheung, Bernard M Y

    2009-01-01

    Obesity is associated with increased risk of conditions such as hypertension, dyslipidaemia, diabetes mellitus, and obstructive sleep apnoea. Pharmacotherapy for obesity should be considered in combination with lifestyle changes in obese patients, or overweight patients with other conditions that put them at risk of developing heart disease. Sibutramine and orlistat are the only two anti-obesity medications approved for long-term use. Sibutramine is a serotonergic and adrenergic drug that reduces food intake. Orlistat is a gastrointestinal lipase inhibitor that interferes with fat absorption. However, it commonly causes flatulence and diarrhoea. Rimonabant is the first of a series of endocannabinoid receptor antagonists. It was approved by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMEA) as an adjunct to diet and exercise in treating obesity in 2006. However, despite the extensive clinical trial data, EMEA announced in 2008 that it has recommended suspension of rimonabant because of its psychiatric side effects. Studies evaluating the long-term safety and efficacy of anti-obesity agents are needed. PMID:20002075

  20. [Contraception and obesity].

    PubMed

    Lobert, M; Pigeyre, M; Gronier, H; Catteau-Jonard, S; Robin, G

    2015-11-01

    The prevalence of obesity is increasing massively over several decades in industrialized countries. Obese women are sexually active but they use fewer contraceptive methods and are at high risk of unintended pregnancy. In addition, obesity is an important risk factor for venous thromboembolism events and arterial thrombosis (myocardial infarction and ischemic stroke). All of these data are to be considered in choosing a contraceptive method for obese women. Except depot medroxyprogesterone acetate injection, the progestin-only contraceptives (progestin only pills and etonogestrel subdermal implant) and the intra-uterine devices are the preferred contraceptive methods in obese women. The combined estrogen-progestin contraceptives (pill, patch and vaginal ring) may be proposed in very strict conditions (no other associated vascular risk factor). Obesity does not increase the risk of failure of most contraceptive methods. Bariatric surgery is a complex situation. It requires to program a possible pregnancy and contraception is needed for several months. Some bariatric surgical techniques such as by-pass can induce gastrointestinal malabsorption. In this situation, all oral contraceptives are not recommended because of a higher risk of failure.

  1. Sarcopenia and sarcopenic obesity

    PubMed Central

    Choi, Kyung Mook

    2016-01-01

    Sarcopenia is an age-associated loss of muscle mass and decline in muscle strength; it is common in older adults and is associated with significant morbidity and mortality. Despite its prevalence, there is currently no universally adopted definition of sarcopenia. In addition to low muscle mass measurements, recent research has recognized the importance of muscle strength and physical performance. Aging induces changes in body composition, such as an increase in visceral fat and reduced muscle mass. Recently, the new concept of sarcopenic obesity has emerged, reflecting a combination of sarcopenia and obesity. The rapidly increasing prevalence and serious consequences of sarcopenic obesity are recognized as a critical public health risk in the aging society. Sarcopenia and obesity share several pathophysiological mechanisms, and they may potentiate each other. The present paper reviews the definitions and techniques used to measure sarcopenia, as well as the health outcomes of sarcopenic obesity. It also highlights the role of diminished muscle mass and strength in cardiometabolic disease mortality. Additional research may be needed to promote the identification and management of sarcopenia and sarcopenic obesity in the elderly population. PMID:27809450

  2. [Inequality, poverty and obesity].

    PubMed

    Ferreira, Vanessa Alves; Silva, Aline Elizabeth; Rodrigues, Chrystiellen Ayana Aparecida; Nunes, Nádia Lúcia Almeida; Vigato, Tássia Cassimiro; Magalhães, Rosana

    2010-06-01

    National studies have been demonstrating the positive relationship among inequality, poverty and obesity revealing the singularities and complexity of the nutritional transition in Brazil. In this direction, the women constitute a vulnerable group to the dynamics of the obesity in the poverty context. Such fact imposes the theoretical deepening and the accomplishment of researches that make possible a larger approach with the phenomenon in subject. In this perspective, the study analyzed the daily life of poor and obese women, users of basic units of health of the city of Diamantina, Vale do Jequitinhonha, Minas Gerais State. The results revealed the complex relationship between feminine obesity and poverty. The cultural and material aspects of life, as well as the different feeding and body conceptions that demonstrated to be fundamental elements for the analysis of the multiple faces of the obesity among the investigated group. Facing these results it is appropriate to encourage public policies that promote equity widening the access of those groups to the main resources for the prevention and combat of obesity.

  3. OBESITY AND VASCULAR DYSFUNCTION

    PubMed Central

    Stapleton, Phoebe A.; James, Milinda E.; Goodwill, Adam G.; Frisbee, Jefferson C.

    2008-01-01

    One of the most profound challenges facing public health and public health policy in Western society is the increased incidence and prevalence of both overweight and obesity. While this condition can have significant consequences for patient mortality and quality of life, it can be further exacerbated as overweight/obesity can be a powerful stimulus for the development of additional risk factors for a negative cardiovascular outcome, including increased insulin resistance, dyslipidemia and hypertension. This manuscript will present the effects of systemic obesity on broad issues of vascular function in both afflicted human populations and in the most relevant animal models. Among the topics that will be covered are alterations to vascular reactivity (both dilator and constrictor responses), adaptations in microvascular network and vessel wall structure, and alterations to the patterns of tissue/organ perfusion as a result of the progression of the obese condition. Additionally, special attention will be paid to the contribution of chronic inflammation as a contributor to alterations in vascular function, as well as the role of perivascular adipose tissue in terms of impacting vessel behavior. When taken together, it is clearly apparent that the development of the obese condition can have profound, and frequently difficult to predict, impacts on integrated vascular function. Much of this complexity appears to have its basis in the extent to which other co-morbidities associated with obesity (e.g., insulin resistance) are present and exert contributing effects. PMID:18571908

  4. Obesity prevention in children.

    PubMed

    Moreno, Luis A; Bel-Serrat, Silvia; Santaliestra-Pasías, Alba M; Rodríguez, Gerardo

    2013-01-01

    The prevalence of childhood overweight and obesity continues to be unacceptably high and of public health concern in Europe. During childhood and adolescence, environmental factors are the main drivers of obesity development. Obesity is caused by a chronic energy imbalance involving both dietary intake and physical activity patterns. Several risk factors are influencing obesity development, even starting in the prenatal period. From birth, along life, mainly diet and physical activity/inactivity are the most important drivers on top of genetic susceptibility. The first years of life can therefore be crucial to start preventive interventions that can have an impact on lifestyle and on later overweight and obesity. Schools are an attractive and popular setting for implementing interventions for children. Interventions including a community component are considered to be the most effective. Obesity control will require policy interventions to improve the environments that promote poor dietary intake and physical inactivity rather than individually focused interventions. More solid institutional and health policies are needed together with more effective interventions to obtain evident changes for the prevention of excess adiposity among children.

  5. Prebiotics in obesity.

    PubMed

    Carnahan, S; Balzer, A; Panchal, S K; Brown, L

    2014-06-01

    Obesity was probably rare in ancient times, with the current increase starting in the Industrial Revolution of the eighteenth century, and becoming much more widespread from about 1950, so concurrent with the increased consumption of carbohydrates from cereals in the Green Revolution. However, dietary components such as oligosaccharides from plants including cereals may improve health following fermentation to short-chain carboxylic acids in the intestine by bacteria which constitute of the microbiome. Such non-digestible and fermentable components of diet, called prebiotics, have been part of the human diet since at least Palaeolithic times, and include components of the cereals domesticated in the Neolithic Revolution. If consumption of these cereals has now increased, why is obesity increasing? One reason could be lowered prebiotic intake combined with increased intake of simple sugars, thus changing the bacteria in the microbiome. Processing of food has played an important role in this change of diet composition. Since obesity is a low-grade inflammation, changing the microbiome by increased consumption of simple carbohydrates and saturated fats may lead to obesity via increased systemic inflammation. Conversely, there is now reasonable evidence that increased dietary prebiotic intake decreases inflammation, improves glucose metabolism and decreases obesity. Would widespread increases in prebiotics in the modern diet, so mimicking Palaeolithic or Neolithic nutrition, decrease the incidence and morbidity of obesity in our communities?

  6. Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

    PubMed Central

    Beck, B

    2006-01-01

    Neuropeptide Y (NPY) is one the most potent orexigenic peptides found in the brain. It stimulates food intake with a preferential effect on carbohydrate intake. It decreases latency to eat, increases motivation to eat and delays satiety by augmenting meal size. The effects on feeding are mediated through at least two receptors, the Y1 and Y5 receptors. The NPY system for feeding regulation is mostly located in the hypothalamus. It is formed of the arcuate nucleus (ARC), where the peptide is synthesized, and the paraventricular (PVN), dorsomedial (DMN) and ventromedial (VMN) nuclei and perifornical area where it is active. This activity is modulated by the hindbrain and limbic structures. It is dependent on energy availability, e.g. upregulation with food deprivation or restriction, and return to baseline with refeeding. It is also sensitive to diet composition with variable effects of carbohydrates and fats. Leptin signalling and glucose sensing which are directly linked to diet type are the most important factors involved in its regulation. Absence of leptin signalling in obesity models due to gene mutation either at the receptor level, as in the Zucker rat, the Koletsky rat or the db/db mouse, or at the peptide level, as in ob/ob mouse, is associated with increased mRNA abundance, peptide content and/or release in the ARC or PVN. Other genetic obesity models, such as the Otsuka–Long–Evans–Tokushima Fatty rat, the agouti mouse or the tubby mouse, are characterized by a diminution in NPY expression in the ARC nucleus and by a significant increase in the DMN. Further studies are necessary to determine the exact role of NPY in these latter models. Long-term exposure to high-fat or high-energy palatable diets leads to the development of adiposity and is associated with a decrease in hypothalamic NPY content or expression, consistent with the existence of a counter-regulatory mechanism to diminish energy intake and limit obesity development. On the other hand, an

  7. American Board of Obesity Medicine (ABOM)

    MedlinePlus

    ... Obesity-Related CME American Society for Metabolic and Bariatric Surgery Canadian Obesity Network Cleveland Clinic Obesity Summit Massachusetts ... Society Public Health American Society of Metabolic and Bariatric Surgery Foundation Global Obesity Prevention Center at Johns Hopkins ...

  8. Metabolomics Study of Type 2 Diabetes Mellitus and the AntiDiabetic Effect of Berberine in Zucker Diabetic Fatty Rats Using Uplc-ESI-Hdms.

    PubMed

    Dong, Yu; Chen, Yi-Tao; Yang, Yuan-Xiao; Zhou, Xiao-Jie; Dai, Shi-Jie; Tong, Jun-Feng; Shou, Dan; Li, Changyu

    2016-05-01

    The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti-diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra-performance liquid chromatography/electrospray ionization synapt high-definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as 'differentiating metabolites' with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near-normal state. These results suggested that the anti-diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5'-monophosphate-activated protein kinase. Our work not only provides a better understanding of the anti-diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Glucomannan- and glucomannan plus spirulina-enriched pork affect liver fatty acid profile, LDL receptor expression and antioxidant status in Zucker fa/fa rats fed atherogenic diets

    PubMed Central

    González-Torres, Laura; Matos, Cátia; Vázquez-Velasco, Miguel; Santos-López, Jorge A.; Sánchez-Martínez, Iria; García–Fernández, Camino; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J.

    2017-01-01

    ABSTRACT We evaluated the effects of glucomannan or glucomannan plus spirulina-restructured pork (RP) on liver fatty acid profile, desaturase/elongase enzyme activities and oxidative status of Zucker fa/fa rats for seven weeks. Control (C), glucomannan (G) and glucomannan/spirulina (GS)-RP; HC (cholesterol-enriched control), HG and HGS (cholesterol-enriched glucomannan and glucomannan/spirulina-RP) experimental diets were tested. Increased metabolic syndrome markers were found in C, G and GS rats. Cholesterol feeding increased liver size, fat, and cholesterol and reduced antioxidant enzyme levels and expressions. Cholesterolemia was lower in HG and HGS than in HC. GS vs. G showed higher stearic but lower oleic levels. SFA and PUFA decreased while MUFA increased by cholesterol feeding. The arachidonic/linoleic and docosahexaenoic/alpha-linolenic ratios were lower in HC, HG, and HGS vs. C, G, and GS, respectively, suggesting a delta-6-elongase-desaturase system inhibition. Moreover, cholesterol feeding, mainly in HGS, decreased low-density-lipoprotein receptor expression and the delta-5-desaturase activity and increased the delta-9-desaturase activity. In conclusion, the liver production of highly unsaturated fatty acids was limited to decrease their oxidation in presence of hypercholesterolaemia. Glucomannan or glucomannan/spirulina-RP has added new attributes to their functional properties in meat, partially arresting the negative effects induced by high-fat-high-cholesterol feeding on the liver fatty acid and antioxidant statuses. PMID:28325998

  10. The worldwide obesity epidemic.

    PubMed

    James, P T; Leach, R; Kalamara, E; Shayeghi, M

    2001-11-01

    The recent World Health Organization (WHO) agreement on the standardized classification of overweight and obese, based on body mass index (BMI), allows a comparable analysis of prevalence rates worldwide for the first time. In Asia, however, there is a demand for a more limited range for normal BMIs (i.e., 18.5 to 22.9 kg/m(2) rather than 18.5 to 24.9 kg/m(2)) because of the high prevalence of comorbidities, particularly diabetes and hypertension. In children, the International Obesity Task-Force age-, sex-, and BMI-specific cutoff points are increasingly being used. We are currently evaluating BMI data globally as part of a new millennium analysis of the Global Burden of Disease. WHO is analyzing data in terms of 20 or more principal risk factors contributing to the primary causes of disability and lost lives in the 191 countries within the WHO. The prevalence rates for overweight and obese people are different in each region, with the Middle East, Central and Eastern Europe, and North America having higher prevalence rates. In most countries, women show a greater BMI distribution with higher obesity rates than do men. Obesity is usually now associated with poverty, even in developing countries. Relatively new data suggest that abdominal obesity in adults, with its associated enhanced morbidity, occurs particularly in those who had lower birth weights and early childhood stunting. Waist measurements in nationally representative studies are scarce but will now be needed to estimate the full impact of the worldwide obesity epidemic.

  11. Microbiota and Obesity.

    PubMed

    Isolauri, Erika

    2017-01-01

    Obesity is globally the most prevalent nutritional disorder. Multifaceted therapeutic approaches are called for to halt the cascade from neonatal adiposity/high birth weight to childhood excessive weight gain/adult obesity with comorbidities. Recent experimental and clinical data provide one new target for interventions aiming to close this vicious circle: the microbiota. An aberrant gut microbiota, dysbiosis, induces immune and metabolic disturbances both locally and, consequent upon impaired gut barrier function, also systemic low-grade inflammation, which is causally linked to insulin resistance. The gut microecology could thus fill the gap between energy intake and expenditure by processing nutrients and regulating their access to and storage in the body, producing chemicals of hormonal nature and controlling the secretion of proinflammatory mediators locally and systemically. Conversely, being highly sensitive to environmental impacts, particularly to early feeding, the compositional development of the gut microbiota may prove the target of choice in efforts to reduce the risk of obesity. It has been demonstrated that a lower number of bifidobacteria precedes the development of obesity, and a dearth of butyrate-producing bacteria and an overall richness of bacteria increase the risk of metabolic disease; moreover, recognition that practices known to disrupt the early gut microbiota, e.g., cesarean section delivery and antibiotic exposure, contribute to obesity, encourages to pursue this line of research.

  12. Mood, food, and obesity

    PubMed Central

    Singh, Minati

    2014-01-01

    Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA) production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity. PMID:25225489

  13. Exercise and obesity.

    PubMed

    McInnis, K J

    2000-03-01

    The prevalence of obesity has increased dramatically during the past decade in the USA. This is despite an estimated 50 million Americans who try to lose weight each year. The increasing prevalence of obesity is particularly alarming due to the numerous health implications associated with this condition, including coronary artery disease, hypertension, diabetes, hyperlipidemia, cancer, and various musculoskeletal conditions. The economic impact of treating illnesses associated with obesity has been estimated to be US$40 billion in the USA. Dieting is largely ineffective in maintaining initial weight loss as numerous studies suggest the majority of dieters regain all lost weight with 3-5 years. On, the other hand, regular exercise has been shown to be one of the best predictors of successful weight maintenance. Moreover, studies indicate that improved fitness through regular physical activity reduces cardiovascular morbidity and mortality for overweight individuals even if they remain overweight. Providing advice about exercise to overweight or obese individuals requires explicit information about the frequency, intensity, duration, and type of physical activity that should be performed. The ultimate goal for the exercising obese patient is to make a life-long commitment to achieving reasonable energy expenditure through routine physical activity.

  14. Obesity: epigenetic aspects.

    PubMed

    Kaushik, Prashant; Anderson, James T

    2016-06-01

    Epigenetics, defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence has been shown to play an important role in the etiopathogenesis of obesity. Obesity is associated with extensive gene expression changes in tissues throughout the body. Epigenetics is emerging as perhaps the most important mechanism through which the lifestyle-choices we make can directly influence the genome. Considerable epidemiological, experimental and clinical data have been amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. In addition to the 'maternal' interactions, there has been increasing interest in the epigenetic mechanisms through which 'paternal' influences on offspring development can be achieved. Nutrition, among many other environmental factors, is a key player that can induce epigenetic changes not only in the directly exposed organisms but also in subsequent generations through the transgenerational inheritance of epigenetic traits. 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. Fortunately, epigenetic phenomena are dynamic and rather quickly reversible with intensive lifestyle changes. This is a very promising and sustainable resolution to the obesity pandemic.

  15. Personalized nutrition and obesity

    PubMed Central

    Qi, Lu

    2017-01-01

    The past few decades have witnessed a rapid rise in nutrition-related disorders such as obesity in the United States and over the world. Traditional nutrition research has associated various foods and nutrients with obesity. Recent advances in genomics have led to identification of the genetic variants determining body weight and related dietary factors such as intakes of energy and macronutrients. In addition, compelling evidence has lent support to interactions between genetic variations and dietary factors in relation to obesity and weight change. Moreover, recently emerging data from other ‘omics’ studies such as epigenomics and metabolomics suggest that more complex interplays between the global features of human body and dietary factors may exist at multiple tiers in affecting individuals’ susceptibility to obesity; and a concept of ‘personalized nutrition’ has been proposed to integrate this novel knowledge with traditional nutrition research, with the hope ultimately to endorse person-centric diet intervention to mitigate obesity and related disorders. PMID:24716734

  16. [Childhood obesity and dyslipidemia].

    PubMed

    Gómez-Díaz, Rita Angélica; Wacher-Rodarte, Niels H

    2014-01-01

    Screening and treatment of plasma lipid abnormalities secondary to obesity are among the interventions that should be implemented in children who are overweight or obese, in order to prevent a cardiovascular event. Dyslipidemias are a group of asymptomatic diseases that are commonly caused by abnormal levels of lipoproteins in blood; they are a comorbidity that is commonly related to obesity, without considering the age of the patient. Among dyslipidemias, hypertriglyceridemia has the highest prevalence. The etiology of the dyslipidemia should be identified; it allows the proper selection of therapy for the patients and their family. The goal is the prevention of cardiovascular complications. Reduced caloric intake and a structured physical activity plan should be considered for initial treatment for all the overweight and obese patients. For adherence to treatment to be successful, the participation of the primary care physician and a multidisciplinary team is required. With treatment, the risks and complications can be reduced. The participation of a specialist in handling the pediatric obese patient with dyslipidemia should be limited to severe cases or those at risk for having pancreatitis.

  17. TENDINOPATHY AND OBESITY

    PubMed Central

    CASTRO, Adham do Amaral e; SKARE, Thelma Larocca; NASSIF, Paulo Afonso Nunes; SAKUMA, Alexandre Kaue; BARROS, Wagner Haese

    2016-01-01

    ABSTRACT Introduction: Tendinopathies and tendon tears account for over 30% of all musculoskeletal consultations. Obesity, which is becoming one of the world´s most prevalent public health issues, may be associated with this condition. Objective: To review the literature about tendinopathies and obesity association. Methods: This is a descriptive exploratory study using the portal Medline. Literature in English language from 2006 to 2014 were reviewed. Results: The pathogenesis of tendinopathies includes inflammatory, regenerative and degenerative processes that happen simultaneously from early to late phases of the disease. Mechanical stress upon tendons seems to be one of the most important factors to initiate the inflammatory response, but it´s not the only one that can deflagrate it: there are other extrinsic, genetic and metabolic factors that may be involved. Therefore, tendinopathies in obese patients can be due to tendon overload because of the excess of weight, but also because of increased production of pro-inflammatory mediators related to fat tissue such as adipokines. This pro-inflammatory state that obese people can suffer is known as adiposopathy, or sick fat syndrome. Weight loss is associated with decrease in adipokines and improvement of musculoskeletal symptoms. Conclusion: The relation of obesity and tendinopathies is supported by evidences of recent studies, exemplified in this review of literature. PMID:27683789

  18. Energy Balance and Obesity

    PubMed Central

    Hill, James O.; Wyatt, Holly R.; Peters, John C.

    2012-01-01

    This paper describes the interplay among energy intake, energy expenditure and body energy stores and illustrates how an understanding of energy balance can help develop strategies to reduce obesity. First, reducing obesity will require modifying both energy intake and energy expenditure and not simply focusing on either alone. Food restriction alone will not be effective in reducing obesity if human physiology is biased toward achieving energy balance at a high energy flux (i.e. at a high level of energy intake and expenditure). In previous environments a high energy flux was achieved with a high level of physical activity but in today's sedentary environment it is increasingly achieved through weight gain. Matching energy intake to a high level of energy expenditure will likely be more a more feasible strategy for most people to maintain a healthy weight than restricting food intake to meet a low level of energy expenditure. Second, from an energy balance point of view we are likely to be more successful in preventing excessive weight gain than in treating obesity. This is because the energy balance system shows much stronger opposition to weight loss than to weight gain. While large behavior changes are needed to produce and maintain reductions in body weight, small behavior changes may be sufficient to prevent excessive weight gain. In conclusion, the concept of energy balance combined with an understanding of how the body achieves balance may be a useful framework in helping develop strategies to reduce obesity rates. PMID:22753534

  19. Intestinal microbiota and obesity.

    PubMed

    Blaut, Michael; Klaus, Susanne

    2012-01-01

    The human gut harbors a highly diverse microbial ecosystem of approximately 400 different species, which is characterized by a high interindividual variability. The intestinal microbiota has recently been suggested to contribute to the development of obesity and the metabolic syndrome. Transplantation of gut microbiota from obese mice to nonobese, germ-free mice resulted in transfer of metabolic syndrome-associated features from the donor to the recipient. Proposed mechanisms for the role of gut microbiota include the provision of additional energy by the conversion of dietary fiber to short-chain fatty acids, effects on gut-hormone production, and increased intestinal permeability causing elevated systemic levels of lipopolysaccharides (LPS). This metabolic endotoxemia is suggested to contribute to low-grade inflammation, a characteristic trait of obesity and the metabolic syndrome. Finally, activation of the endocannabinoid system by LPS and/or high-fat diets is discussed as another causal factor. In conclusion, there is ample evidence for a role of gut microbiota in the development of obesity in rodents. However, the magnitude of its contribution to human obesity is still unknown.

  20. 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.

  1. 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

  2. OBESITY: OVERVIEW OF AN EPIDEMIC

    PubMed Central

    Mitchell, Nia; Catenacci, Vicki; Wyatt, Holly R.; Hill, James O.

    2011-01-01

    SYNOPSIS Despite growing recognition of the problem, the obesity epidemic continues in the U.S., and obesity rates are increasing around the world. The latest estimates are that approximately 34% of adults and 15–20% of children and adolescents in the U.S. are obese. Obesity affects every segment of the U.S. population. Obesity increases the risk of many chronic diseases in children and adults. The epidemic of obesity arose gradually over time, apparently from a small, consistent degree of positive energy balance. Substantial public health efforts are being directed toward addressing obesity, but there is not yet clear evidence of success. Because of the complexity of obesity, it is likely to be one of the most difficult public health issues our society has faced. PMID:22098799

  3. Causes of obesity.

    PubMed

    Wright, Suzanne M; Aronne, Louis J

    2012-10-01

    The prevalence of obesity has been rising steadily over the last several decades and is currently at unprecedented levels: more than 68% of US adults are considered overweight, and 35% are obese (Flegal et al., JAMA 303:235-241, 2010). This increase has occurred across every age, sex, race, and smoking status, and data indicate that segments of individuals in the highest weight categories (i.e., BMI > 40 kg/m(2)) have increased proportionately more than those in lower BMI categories (BMI < 35 kg/m(2)). The dramatic rise in obesity has also occurred in many other countries, and the causes of this increase are not fully understood (Hill and Melanson, Med Sci Sports Exerc 31:S515-S521, 1999).

  4. Sleep debt and obesity.

    PubMed

    Bayon, Virginie; Leger, Damien; Gomez-Merino, Danielle; Vecchierini, Marie-Françoise; Chennaoui, Mounir

    2014-08-01

    Short sleep duration has been shown to be associated with elevated body mass index (BMI) in many epidemiological studies. Several pathways could link sleep deprivation to weight gain and obesity, including increased food intake, decreased energy expenditure, and changes in levels of appetite-regulating hormones, such as leptin and ghrelin. A relatively new factor that is contributing to sleep deprivation is the use of multimedia (e.g. television viewing, computer, and internet), which may aggravate sedentary behavior and increase caloric intake. In addition, shift-work, long working hours, and increased time commuting to and from work have also been hypothesized to favor weight gain and obesity-related metabolic disorders, because of their strong link to shorter sleep times. This article reviews the epidemiological, biological, and behavioral evidence linking sleep debt and obesity.

  5. Bias, discrimination, and obesity.

    PubMed

    Puhl, R; Brownell, K D

    2001-12-01

    This article reviews information on discriminatory attitudes and behaviors against obese individuals, integrates this to show whether systematic discrimination occurs and why, and discusses needed work in the field. Clear and consistent stigmatization, and in some cases discrimination, can be documented in three important areas of living: employment, education, and health care. Among the findings are that 28% of teachers in one study said that becoming obese is the worst thing that can happen to a person; 24% of nurses said that they are "repulsed" by obese persons; and, controlling for income and grades, parents provide less college support for their overweight than for their thin children. There are also suggestions but not yet documentation of discrimination occurring in adoption proceedings, jury selection, housing, and other areas. Given the vast numbers of people potentially affected, it is important to consider the research-related, educational, and social policy implications of these findings.

  6. Gut microbiota and obesity.

    PubMed

    Gérard, Philippe

    2016-01-01

    The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

  7. Muscle development and obesity

    PubMed Central

    2008-01-01

    The formation of skeletal muscle from the epithelial somites involves a series of events triggered by temporally and spatially discrete signals resulting in the generation of muscle fibers which vary in their contractile and metabolic nature. The fiber type composition of muscles varies between individuals and it has now been found that there are differences in fiber type proportions between lean and obese animals and humans. Amongst the possible causes of obesity, it has been suggested that inappropriate prenatal environments may ‘program’ the fetus and may lead to increased risks for disease in adult life. The characteristics of muscle are both heritable and plastic, giving the tissue some ability to adapt to signals and stimuli both pre and postnatally. Given that muscle is a site of fatty acid oxidation and carbohydrate metabolism and that its development can be changed by prenatal events, it is interesting to examine the possible relationship between muscle development and the risk of obesity. PMID:19279728

  8. Obesity and fertility.

    PubMed

    Best, Damian; Bhattacharya, Siladitya

    2015-10-01

    The prevalence of overweight and obesity in women of reproductive age has increased over the past 30 years. Infertility affects 1 in 7 couples, and female obesity is associated with anovulation. The mechanisms by which excessive fat delays time to pregnancy (TTP) appear rooted in ovulatory problems and direct effects on oocytes, causing poorer embryo development, as well as in effects on the endometrium. Weight loss in women has been shown to improve conception, but not necessarily live birth rates following fertility treatment, and further research in this area is needed. The obesity epidemic has been accompanied by a potential rise in male infertility, which has been attributed to hormonal disturbances and compromised semen parameters.

  9. [Obesity and hypertension].

    PubMed

    Simonyi, Gábor; Kollár, Réka

    2013-11-03

    The frequency of hypertension and obesity is gradually growing in Hungary. At present 68.5% of men and 78% of women are obese. Hypertension and obesity are the most important risk factors of morbidity and mortality from cardiovascular disease. The relationship between increased sympathetic activity and hypertension is well known. Waist circumference and body fat mass correlate significantly with sympathetic activity, in which hyperlipidemia plays also a role. The increased activity of renin-angiotensin-aldosterone system via its vascular and renal effects also contributes to an increase of blood pressure. Increased sympathetic activity with decreasing vagal tone accompanying the imbalance of the autonomous nervous system is independent and significant risk factor of cardiovascular events including sudden cardiac death.

  10. Epigenetics and obesity.

    PubMed

    Campión, Javier; Milagro, Fermin; Martínez, J Alfredo

    2010-01-01

    The etiology of obesity is multifactorial, involving complex interactions among the genetic makeup, neuroendocrine status, fetal programming, and different unhealthy environmental factors, such as sedentarism or inadequate dietary habits. Among the different mechanisms causing obesity, epigenetics, defined as the study of heritable changes in gene expression that occur without a change in the DNA sequence, has emerged as a very important determinant. Experimental evidence concerning dietary factors influencing obesity development through epigenetic mechanisms has been described. Thus, identification of those individuals who present with changes in DNA methylation profiles, certain histone modifications, or other epigenetically related processes could help to predict their susceptibility to gain or lose weight. Indeed, research concerning epigenetic mechanisms affecting weight homeostasis may play a role in the prevention of excessive fat deposition, the prediction of the most appropriate weight reduction plan, and the implementation of newer therapeutic approaches.

  11. Obesity hypoventilation syndrome.

    PubMed

    Al Dabal, Laila; Bahammam, Ahmed S

    2009-04-01

    Obesity is becoming a major medical concern in several parts of the world, with huge economic impacts on health- care systems, resulting mainly from increased cardiovascular risks. At the same time, obesity leads to a number of sleep-disordered breathing patterns like obstructive sleep apnea and obesity hypoventilation syndrome (OHS), leading to increased morbidity and mortality with reduced quality of life. OHS is distinct from other sleep- related breathing disorders although overlap may exist. OHS patients may have obstructive sleep apnea/hypopnea with hypercapnia and sleep hypoventilation, or an isolated sleep hypoventilation. Despite its major impact on health, this disorder is under-recognized and under-diagnosed. Available management options include aggressive weight reduction, oxygen therapy and using positive airway pressure techniques. In this review, we will go over the epidemiology, pathophysiology, presentation and diagnosis and management of OHS.

  12. Obesity and Autism

    PubMed Central

    Zuckerman, Katharine E.; Fombonne, Eric

    2015-01-01

    OBJECTIVE: Overweight and obesity are increasingly prevalent in the general pediatric population. Evidence suggests that children with autism spectrum disorders (ASDs) may be at elevated risk for unhealthy weight. We identify the prevalence of overweight and obesity in a multisite clinical sample of children with ASDs and explore concurrent associations with variables identified as risk factors for unhealthy weight in the general population. METHODS: Participants were 5053 children with confirmed diagnosis of ASD in the Autism Speaks Autism Treatment Network. Measured values for weight and height were used to calculate BMI percentiles; Centers for Disease Control and Prevention criteria for BMI for gender and age were used to define overweight and obesity (≥85th and ≥95th percentiles, respectively). RESULTS: In children age 2 to 17 years, 33.6% were overweight and 18% were obese. Compared with a general US population sample, rates of unhealthy weight were significantly higher among children with ASDs ages 2 to 5 years and among those of non-Hispanic white origin. Multivariate analyses revealed that older age, Hispanic or Latino ethnicity, lower parent education levels, and sleep and affective problems were all significant predictors of obesity. CONCLUSIONS: Our results indicate that the prevalence of unhealthy weight is significantly greater among children with ASD compared with the general population, with differences present as early as ages 2 to 5 years. Because obesity is more prevalent among older children in the general population, these findings raise the question of whether there are different trajectories of weight gain among children with ASDs, possibly beginning in early childhood. PMID:26527551

  13. Childhood Obesity: The Caregiver's Role.

    ERIC Educational Resources Information Center

    Haschke, Bernadette

    2003-01-01

    Describes the role caregivers play in helping young children dealing with obesity. Examines: (1) causes of childhood obesity; (2) caregiver's position; (3) learning nutrition concepts; (4) preparing and serving healthy foods; (5) encouraging physical activity; (6) working with parents; and (7) assisting an obese child. (SD)

  14. Childhood Obesity: Prediction and Prevention.

    ERIC Educational Resources Information Center

    Miller, Michael D.

    Obesity in children is a problem both insidious and acute. Childhood obesity has been indicated as a forerunner of adult obesity; it is also an immediate problem for the child. Given the lack of evidence for long term maintenance of any weight loss, this paper investigates the etiology of the disorder as a prelude to prevention. Upon review of the…

  15. The Medical Aspects of Obesity.

    ERIC Educational Resources Information Center

    Eichold, Samuel

    Obesity is one of the leading public health problems in the United States. It is associated with drug abuse and increased mortality. In seeking to differentiate between overweight and obese individuals, it may be said that obesity exists in those individuals who are 40% or more above normal weight as determined on commonly used height and weight…

  16. Childhood Obesity. Special Reference Briefs.

    ERIC Educational Resources Information Center

    Winick, Myron

    This reference brief deals with the problem of childhood obesity and how it can lead to obesity in the adult. Eighty-four abstracts are presented of studies on the identification, prevention, and treatment of obesity in children, focusing on diet and psychological attitudes. Subjects of the studies were children ranging in age from infancy through…

  17. Fight Obesity in the Classroom

    ERIC Educational Resources Information Center

    Bratsis, Michael E.

    2012-01-01

    U.S. health experts declared obesity an epidemic over a decade ago. Schools have tried to implement prevention programs for students, but as budgets shrink, educating students about obesity is increasingly falling to classroom instructors, including science teachers. The good news is that obesity-related classroom activities can be engaging, and…

  18. Obesity and liver transplantation

    PubMed Central

    Ayloo, Subhashini; Armstrong, John; Hurton, Scott; Molinari, Michele

    2015-01-01

    The percentage of overweight and obese patients (OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation (LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed. PMID:26421262

  19. Nutrition Interventions for Obesity.

    PubMed

    Ard, Jamy D; Miller, Gary; Kahan, Scott

    2016-11-01

    Obesity is a common disorder with complex causes. The epidemic has spurred significant advances in the understanding of nutritional approaches to treating obesity. Although the primary challenge is to introduce a dietary intake that creates an energy deficit, clinicians should also consider targeted risk factor modification with manipulation of the nutrient profile of the weight-reducing diet. These strategies produce significant weight loss and improvements in cardiometabolic risk factors. Future research is needed to better understand how to personalize nutrient prescriptions further to promote optimal risk modification and maintenance of long-term energy balance in the weight-reduced state.

  20. Obesity and renal cancer

    PubMed Central

    Gati, Asma; Kouidhi, Soumaya; Marrakchi, Raja; El Gaaied, Amel; Kourda, Nadia; Derouiche, Amine; Chebil, Mohamed; Caignard, Anne; Perier, Aurélie

    2014-01-01

    Epidemiological studies link obesity, as measured by increased body mass index (BMI) to the incidence of renal cell carcinoma (RCC) as well as to the cancer-related mortality of RCC patients. RCC is the third cancer most robustly associated with increased BMI. Understanding the role of the adipose tissue in renal carcinogenesis is therefore of major importance for the development of novel paradigms of RCC prevention and treatment. Here, we discuss the current knowledge on the impact of obesity on the development and progression of RCC as well as the role of adipose tissue-derived hormones (adipokines) in the conflict between growing tumors and the immune system. PMID:24804162

  1. [Obesity-hypoventilation syndrome].

    PubMed

    Cai, Y; Dong, H; Weng, M

    1996-01-01

    5 cases with obesity-hypoventilaion syndrome were reported. The clinical manifestations were obesity, palpitation, dyspnea, lethargy, cyanosis, distention of cervical vein, edema, enlargement of liver and hypertension. All of them were initially diagnosed as chronic bronchitis or heart diseases. Pulmonary function test showed restrictive ventilative defect and hypercapnia with hypoxemia. Mouth oclusion pressure at 0.1 second was higher than the normal value. The response to CO2 was decreased. Hypertrophy of right heart was shown in ECG and X-ray film improvement in symptoms and blood gases analyses were found to be associated with body weight decrease in a follow up period of one year.

  2. 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.

  3. 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

  4. The Future of Pediatric Obesity.

    PubMed

    Hutchinson, Jeff; Emerick, Jill; Saxena, Harshita

    2016-03-01

    The National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention reports a steady increase in obesity over the last 30 years. The greatest increase was seen in 15 to 19 year olds, whose obesity prevalence almost doubled from 10.5% to 19.4%. The solution to pediatric obesity requires a multidisciplinary approach addressing cultural norms, technologic advances, and family engagement. Future treatment strategies to combat the obesity epidemic will have to extend beyond the health care provider's office. Behavior modification remains the key component to pediatric obesity prevention and treatment.

  5. Metabolic imprinting in obesity.

    PubMed

    Sullivan, E L; Grove, K L

    2010-01-01

    Increasing evidence indicates that early metabolic programming contributes to escalating obesity rates in children and adults. Metabolic imprinting is involved in the establishment of set points for physiologic and metabolic responses in adulthood. Evidence from epidemiological studies and animal models indicates that maternal health and nutritional status during gestation and lactation have long-term effects on central and peripheral systems that regulate energy balance in the developing offspring. Perinatal nutrition also impacts susceptibility to developing metabolic disorders and plays a role in programming body weight set points. The states of maternal energy status and health that are implicated in predisposing offspring to increased risk of developing obesity include maternal overnutrition, diabetes, and undernutrition. This chapter discusses the evidence from epidemiologic studies and animal models that each of these states of maternal energy status results in metabolic imprinting of obesity in offspring. Also, the potential molecular mediators of metabolic imprinting of obesity by maternal energy status including glucose, insulin, leptin, inflammatory cytokines and epigenetic mechanisms are considered.

  6. Multi-Caused Obesity

    ERIC Educational Resources Information Center

    Lewis, Anne C.

    2006-01-01

    Headlines recently were full of studies about the obesity problem of America's children and young people, as if kids became overweight without anyone noticing. An accumulation of both school and family habits, however, have been contributing to the fact that at least 13% of children ages 7 to 11 are overweight, double those of the 1970s (and…

  7. [Inflammation and obesity (lipoinflammation)].

    PubMed

    Izaola, Olatz; de Luis, Daniel; Sajoux, Ignacio; Domingo, Joan Carles; Vidal, Montse

    2015-06-01

    Obesity is a chronic disease with multiple origins. It is a widespread global phenomenon carrying potentially serious complications which requires a multidisciplinary approach due to the significant clinical repercussions and elevated health costs associated with the disease. The most recent evidence indicates that it shares a common characteristic with other prevalent, difficult-to-treat pathologies: chronic, low-grade inflammation which perpetuates the disease and is associated with multiple complications. The current interest in lipoinflammation or chronic inflammation associated with obesity derives from an understanding of the alterations and remodelling that occurs in the adipose tissue, with the participation of multiple factors and elements throughout the process. Recent research highlights the importance of some of these molecules, called pro-resolving mediators, as possible therapeutic targets in the treatment of obesity. This article reviews the evidence published on the mechanisms that regulate the adipose tissue remodelling process and lipoinflammation both in obesity and in the mediators that are directly involved in the appearance and resolution of the inflammatory process.

  8. Liver in obesity.

    PubMed Central

    Braillon, A; Capron, J P; Hervé, M A; Degott, C; Quenum, C

    1985-01-01

    We report on clinical, nutritional, and hepatic histological findings in 50 non-selected obese subjects (mean overweight +74%; range +21-138%). The pathogenesis of the liver damage was assessed with the help of multidimensional analysis of a number of clinical variables. According to the severity of the hepatic lesions, the patients have been ranged in five groups: O (normal liver) 10%; I (fatty liver) 48%; II (fatty hepatitis) 26%; III (fatty fibrosis) 8%; IV (fatty cirrhosis) 8%. The more severe changes (groups III and IV) were constantly associated with excessive alcohol intake. The multidimensional analysis was unable to find a relationship between obesity and the development of fibrosis and cirrhosis whereas it showed that: (a) there was a highly significant correlation between the daily ethanol intake and the degree of overweight, (b) severe fatty metamorphosis was significantly associated with the degree of overweight, the existence of diabetes mellitus, and the amount of alcohol and fat intake, (c) nutritional factors, in particular deficient protein intake, have only an accessory effect in the development of mild inflammation and fibrosis, (d) the consumption of potentially hepatotoxic drugs, very high in the obese (about five drugs per day) could have a role in the development of cirrhosis. In conclusion in our study, there was no evidence that obesity per se could result in severe liver damage. PMID:3967830

  9. [Obesity and cancer].

    PubMed

    Ungefroren, H; Gieseler, F; Lehnert, H

    2015-02-01

    The incidence of obesity in the western world has increased dramatically during recent decades. Epidemiological data suggest that obesity is associated with an increased risk of several but not all types of cancers, with clear sex-specific differences. The underlying mechanisms are still a matter of debate. This review focuses on the potential factors linking obesity to cancer. Current experimental evidence suggests that insulin resistance and a chronic, subclinical inflammation in the visceral fat are the major metabolic events causing alterations in the levels of insulin, glucose, free fatty acids, insulin-like growth factor 1 (IGF-1) and 2, adipose tissue-derived proinflammatory cytokines and other bioactive molecules, such as adipokines (e.g. leptin and adiponectin), vascular endothelial growth factor (VEGF), sex hormones, gut microbiota and secondary bile acids. All these factors may act directly or indirectly on the tumor microenvironment to drive tumor progression via stimulation of cell survival/antiapoptosis, cell proliferation, angiogenesis and invasion/metastasis of the cancer cells. Therapeutic strategies that target dysfunctional or inflamed fat and have been shown to benefit patients include bariatric surgery, while other cell or hormone-directed interventions, such as conversion of visceral fat macrophages to an anti-inflammatory M2 phenotype or the pharmacological modulation of serum adipokine levels are still theoretical and need to be clinically evaluated for their ability to successfully treat or prevent obesity-related cancers.

  10. Obesity, Inflammation and Diet

    PubMed Central

    Lee, Hansongyi; Lee, In Seok

    2013-01-01

    Obesity is a state in which there is an over-accumulation of subcutaneous and/or abdominal adipose tissue. This adipose tissue is no longer considered inert and mainly devoted to storing energy; it is emerging as an active tissue in the regulation of physiological and pathological processes, including immunity and inflammation. Adipose tissue produces and releases a variety of adipokines (leptin, adiponectin, resistin, and visfatin), as well as pro- and anti-inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-4, IL-6, and others). Adipose tissue is also implicated in the development of chronic metabolic diseases such as type 2 diabetes mellitus or cardiovascular disease. Obesity is thus an underlying condition for inflammatory and metabolic diseases. Diet or dietary patterns play critical roles in obesity and other pathophysiological conditions. A healthy diet and some nutrients are generally considered beneficial; however, some dietary nutrients are still considered controversial. In this article, dietary factors that influence inflammation associated with obesity are discussed. PMID:24224147

  11. [Pharmacological treatment of obesity].

    PubMed

    Gomis Barbará, R

    2004-01-01

    The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.

  12. Victimization of Obese Adolescents

    ERIC Educational Resources Information Center

    Robinson, Sabrina

    2006-01-01

    Peer victimization of obese adolescents has been associated with low self-esteem, body dissatisfaction, social isolation, marginalization, poor psychosocial adjustment, depression, eating disorders, and suicidal ideation and attempts, not to mention poor academic performance. Weight-based peer victimization is defined as unsolicited bullying and…

  13. Behavioral management of obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The behavioral management of obesity is an approach designed to provide individuals with a set of skills that promote a healthier weight. A number of strategies are used to assist individuals in making gradual changes that can realistically be incorporated into their lives. Evidence is promising f...

  14. The psychology of obesity.

    PubMed

    Swencionis, Charles; Rendell, Sarah Litman

    2012-10-01

    G. Stanley Hall, the first person to earn a Ph.D. in psychology in the United States, did research on eating behaviors in the nineteenth century (Lepore in The New Yorker, 2011). Research on psychological aspects of obesity accelerated in the 1950s and there has been a great deal done at this point. We review areas of considerable activity and relevance.

  15. Chronobiology and obesity.

    PubMed

    Garaulet, Marta; Gómez-Abellán, Purificación

    2013-09-01

    Chronobiology is a word derived from three Greek stems: kronos for time, bios for life and logos for study. From microarrays studies, now it is accepted that 10-30% of the human genome is under the control of circadian molecular clocks. This implies that most behavioral, physiological and biochemical variables display circadian rhythms in their expression. In its simplest form, circadian clocks are composed of a set of proteins that generate self-sustained circadian oscillations. The molecular clock comprises two transcription factors, CLOCK and BMAL1, whereas PERs and CRYs are responsible for the negative limb. One of the most important questions related to the circadian system and obesity, was to elucidate if adipose tissue displayed circadian rhythmicity or whether it had an internal peripheral clock. Our group of research has provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. A new concept related to illness is Chronodisruption (CD). It is defined as a relevant disturbance of the internal temporal order of physiological and behavioral circadian rhythms. In our modern society, CD may be common in several conditions such as jet lag, shift work, light at night, or social jet lag. In addition clock gene polymorphisms and aging may have also chronodisruptive effects. Our group has also demonstrated that Obesity and CD are also highly interconnected. With the help of chronobiology we can reach a new view of obesity considering not only "what" are the factors involved in obesity, but also "when" these factors are produced.

  16. Games and childhood obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Videogames can be used to help children change their obesity-related diet and physical activity behaviors. A review of the relevant literature in this special issue of the Games for Health Journal indicated that video games did influence children's adiposity, but only among children who were alread...

  17. [Urinary incontinence and obesity].

    PubMed

    Legendre, G; Fritel, X; Capmas, P; Pourcelot, A-G; Fernandez, H

    2012-06-01

    Obesity, defined as a body mass index (BMI) more than or equal to 30kg/m(2), promotes pelvic floor disorders such as urinary incontinence (UI) and genital prolapse. Datas from cohort studies found an association between high BMI and the onset of UI. This association seems to be predominant with for mixed UI and stress UI. For the urge UI and overactive bladder syndrome, the analysis of the literature found a weaker association. The weight is therefore the only modifiable risk factor. Thus, the weight loss by a hypocaloric diet associated with pelvic floor muscle training should be the front line treatment in the obese patient suffering from UI. Bariatric surgery can be discussed in the most obese patient, even if the risk/benefit balance should be weighed because of significant morbidity of this surgery. The results of sub urethral sling (by retropubic tension-free vaginal tape or transobturator sling) in obese patients appear to be equivalent to those obtained in patients of normal weight. Datas on per- and postoperative complications for suburethral slings are reassuring.

  18. Dietary polyphenols and obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The prevalence of overweight and obesity and their associated metabolic disorders are considered a major threat to the public’s health. While several diet and exercise programs are available for weight loss and prevention of weight regain, progresses often slow and disappointing. Recently, natural b...

  19. Obesity and colorectal cancer.

    PubMed

    Aleksandrova, Krasimira; Nimptsch, Katharina; Pischon, Tobias

    2013-01-01

    This review outlines the association of obesity with risk of colorectal cancer and the potential underlying mechanisms from an epidemiological perspective. Current research indicates that there is a moderate but consistently reported association between general obesity (as determined by BMI) and colorectal cancer incidence and mortality. The relative risk associated with obesity is higher for cancer of the colon than for cancer of the rectum and it is higher in men than in women. By contrast, abdominal adiposity (as determined by waist circumference or waist-to-hip ratio) is similarly strongly associated with colon cancer in men and women, suggesting that abdominal adiposity is a more important risk factor for colon cancer than general adiposity, at least in women. Putative mechanisms that may account for the link between adiposity and colorectal cancer risk include hyperinsulinemia, insulin resistance, inflammation, altered immune response, oxidative stress, as well as disturbances in insulin-like growth factors, adipokines, and sex steroids. Understanding the link between obesity and colorectal cancer may pave the way for targeted prevention of colorectal cancer morbidity and mortality.

  20. Dermatological complications of obesity.

    PubMed

    García Hidalgo, Linda

    2002-01-01

    Obesity is a health problem of considerable magnitude in the Western world. Dermatological changes have been reported in patients with obesity, including: acanthosis nigricans and skin tags (due to insulin resistance); hyperandrogenism; striae due to over extension; stasis pigmentation due to peripheral vascular disease; lymphedema; pathologies associated with augmented folds; morphologic changes in the foot anatomy due to excess load; and complications that may arise from hospitalization. Acanthosis nigricans plaques can be managed by improved control of hyperinsulinemia; the vitamin D3 analog calcipitriol has also been shown to be effective. Skin tags can be removed by snipping with curved scissors, by cryotherapy or by electrodesiccation. Hyperandrogenism, a result of increased production of endogenous androgens due to increased volumes of adipose tissue (which synthesizes testosterone) and hyperinsulinemia (which increases the production of ovarian androgens) needs to be carefully assessed to ensure disorders such as virilizing tumors and congenital adrenal hyperplasia are treated appropriately. Treatment of hyperandrogenism should be centred on controlling insulin levels; weight loss, oral contraceptive and antiandrogenic therapies are also possible treatment options. The etiology of striae distensae, also known as stretch marks, is yet to be defined and treatment options are unsatisfactory at present; striae rubra and alba have been treated with a pulsed dye laser with marginal success. The relationship between obesity and varicose veins is controversial; symptoms are best prevented by the use of elastic stockings. Itching and inflammation associated with stasis pigmentation, the result of red blood cells escaping into the tissues, can be treated with corticosteroids. Lymphedema is associated with dilatation of tissue channels, reduced tissue oxygenation and provides a culture medium for bacterial growth. Lymphedema treatment is directed towards reducing the

  1. 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.

  2. The Estrogen Hypothesis of Obesity

    PubMed Central

    Grantham, James P.; Henneberg, Maciej

    2014-01-01

    The explanation of obesity as a simple result of positive energy balance fails to account for the scope of variable responses to diets and lifestyles. It is postulated that individual physiological and anatomical variation may be responsible for developing obesity. Girls in poor families develop greater adiposity than their male siblings, a trend not present in richer environments. This indicates strong influence of estrogen on fat accumulation irrespective of poor socioeconomic conditions. Obesity rates in males and females of developed nations are similar, while in poorer nations obesity is much more prevalent in females. Female to male ratio of obesity correlates inversely with gross domestic product. Therefore, the parity of male and female obesity in developed countries may result from male exposure to environmental estrogen-like substances associated with affluence. These hormonally driven mechanisms may be equally active within both sexes in more developed areas, thereby increasing overall obesity. PMID:24915457

  3. Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion

    PubMed Central

    Wang, May-Yun; Koyama, Kazunori; Shimabukuro, Michio; Mangelsdorf, David; Newgard, Christopher B.; Unger, Roger H.

    1998-01-01

    The high-Km glucose transporter, GLUT-2, and the high-Km hexokinase of β cells, glucokinase (GK), are required for glucose-stimulated insulin secretion (GSIS). GLUT-2 expression in β cells of Zucker diabetic fatty (ZDF) rats is profoundly reduced at the onset of β-cell dysfunction of diabetes. Because ZDF rats are homozygous for a mutation in their leptin receptor (OB-R) gene and are therefore leptin-insensitive, we expressed the wild-type OB-R gene in diabetic islets by infusing a recombinant adenovirus (AdCMV-OB-Rb) to determine whether this reversed the abnormalities. Leptin induced a rise in phosphorylated STAT3, indicating that the transferred wild-type OB-R was functional. GLUT-2 protein rose 17-fold in AdCMV-OB-Rb-treated ZDF islets without leptin, and leptin caused no further rise. GK protein rose 7-fold without and 12-fold with leptin. Preproinsulin mRNA increased 64% without leptin and rose no further with leptin, but leptin was required to restore GSIS. Clofibrate and 9-cis-retinoic acid, the partner ligands for binding to peroxisome proliferator-activator receptor α (PPARα) and retinoid X receptor, up-regulated GLUT-2 expression in islets of normal rats, but not in ZDF rats, in which PPARα is very low. Because the fat content of islets of diabetic ZDF rats remains high unless they are treated with leptin, it appears that restoration of GSIS requires normalization of intracellular nutrient homeostasis, whereas up-regulation of GLUT-2 and GK is leptin-independent, requiring only high expression of OB-Rb. PMID:9751766

  4. TAK-875, a GPR40/FFAR1 agonist, in combination with metformin prevents progression of diabetes and β-cell dysfunction in Zucker diabetic fatty rats

    PubMed Central

    Ito, R; Tsujihata, Y; Matsuda-Nagasumi, K; Mori, I; Negoro, N; Takeuchi, K

    2013-01-01

    BACKGROUND AND PURPOSE TAK-875, a selective GPCR40/free fatty acid receptor 1 agonist, improves glycaemic control by increasing glucose-dependent insulin secretion. Metformin is a first-line drug for treatment of type 2 diabetes that improves peripheral insulin resistance. Based on complementary mechanism of action, combining these agents is expected to enhance glycaemic control. Here, we evaluated the chronic effects of TAK-875 monotherapy and combination therapy with metformin in diabetic rats. EXPERIMENTAL APPROACH Long-term effects on glycaemic control and β-cell function were evaluated using Zucker diabetic fatty (ZDF) rats, which develop diabetes with hyperlipidaemia and progressive β-cell dysfunction. KEY RESULTS Single doses of TAK-875 (3–10 mg·kg−1) and metformin (50–150 mg·kg−1) significantly improved both postprandial and fasting hyperglycaemia, and additive improvements were observed in their combination. Six-week treatment with TAK-875 (10 mg·kg−1, b.i.d.) significantly decreased glycosylated Hb (GHb) by 1.7%, and the effect was additively enhanced by combination with metformin (50 mg·kg−1, q.d.; GHb: −2.4%). This improvement in glycaemic control in the combination group was accompanied by significant 3.2-fold increase in fasting plasma insulin levels. Pancreatic insulin content was maintained at a level comparable to that in normal rats by combination treatment (vehicle: 26, combination: 67.1; normal lean: 69.1 ng·mg−1 pancreas) without affecting pancreatic glucagon content. Immunohistochemical analyses revealed normal morphology, enhanced pancreas duodenum homeobox-1 expression and increased PCNA-positive cells in islets of the combination group. Conclusion and Implications Our results indicate that combination therapy with TAK-875 and metformin could be a valuable strategy for glycaemic control and β-cell preservation in type 2 diabetes. PMID:23848179

  5. Effects of the Soluble Fiber Complex PolyGlycopleX on Glucose Homeostasis and Body Weight in Young Zucker Diabetic Rats.

    PubMed

    Grover, Gary James; Koetzner, Lee; Wicks, Joan; Gahler, Roland J; Lyon, Michael R; Reimer, Raylene A; Wood, Simon

    2011-01-01

    Dietary fiber can reduce insulin resistance, body weight, and hyperlipidemia depending on fiber type, water solubility, and viscosity. PolyGlycopleX(®) (PGX(®)) is a natural, novel water soluble, non-starch polysaccharide complex that with water forms a highly viscous gel compared to other naturally occurring dietary fiber. We determined the effect of dietary PGX(®) vs. cellulose and inulin on the early development of insulin resistance, body weight, hyperlipidemia, and glycemia-induced tissue damage in young Zucker diabetic rats (ZDFs) in fasted and non-fasted states. ZDFs (5 weeks old) were fed a diet containing 5% (wgt/wgt) cellulose, inulin, or PGX(®) for 8 weeks. Body weight, lipids, insulin, and glucose levels were determined throughout the study and homeostasis model assessment (HOMA) was used to measure insulin sensitivity throughout the study in fasted animals. At study termination, insulin sensitivity (oral glucose tolerance test, OGTT) and kidney, liver, and pancreatic histopathology were determined. Body weight and food intake were significantly reduced by PGX(®) vs. inulin and cellulose. Serum insulin in fasted and non-fasted states was significantly reduced by PGX(®) as was non-fasted blood glucose. Insulin resistance, measured as a HOMA score, was significantly reduced by PGX(®) in weeks 5 through 8 as well as terminal OGTT scores in fed and fasted states. Serum total cholesterol was also significantly reduced by PGX(®). PGX(®) significantly reduced histological kidney and hepatic damage in addition to reduced hepatic steatosis and cholestasis. A greater mass of pancreatic β-cells was found in the PGX(®) group. PGX(®) therefore may be a useful dietary additive in the control of the development of the early development of the metabolic syndrome.

  6. A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat.

    PubMed

    Brown, K K; Henke, B R; Blanchard, S G; Cobb, J E; Mook, R; Kaldor, I; Kliewer, S A; Lehmann, J M; Lenhard, J M; Harrington, W W; Novak, P J; Faison, W; Binz, J G; Hashim, M A; Oliver, W O; Brown, H R; Parks, D J; Plunket, K D; Tong, W Q; Menius, J A; Adkison, K; Noble, S A; Willson, T M

    1999-07-01

    The discovery that peroxisome proliferator-activated receptor (PPAR)-gamma was the molecular target of the thiazolidinedione class of antidiabetic agents suggested a key role for PPAR-gamma in the regulation of carbohydrate and lipid metabolism. Through the use of high-throughput biochemical assays, GW1929, a novel N-aryl tyrosine activator of human PPAR-gamma, was identified. Chronic oral administration of GW1929 or troglitazone to Zucker diabetic fatty (ZDF) rats resulted in dose-dependent decreases in daily glucose, free fatty acid, and triglyceride exposure compared with pretreatment values, as well as significant decreases in glycosylated hemoglobin. Whole body insulin sensitivity, as determined by the euglycemic-hyperinsulinemic clamp technique, was significantly increased in treated animals. Comparison of the magnitude of glucose lowering as a function of serum drug concentrations showed that GW1929 was 2 orders of magnitude more potent than troglitazone in vivo. These data were consistent with the relative in vitro potencies of GW1929 and troglitazone. Isolated perfused pancreas studies performed at the end of the study confirmed that pancreata from vehicle-treated rats showed no increase in insulin secretion in response to a step change in glucose from 3 to 10 mmol/l. In contrast, pancreata from animals treated with GW1929 showed a first- and second-phase insulin secretion pattern. Consistent with the functional data from the perfusion experiments, animals treated with the PPAR-gamma agonist had more normal islet architecture with preserved insulin staining compared with vehicle-treated ZDF rats. This is the first demonstration of in vivo efficacy of a novel nonthiazolidinedione identified as a high-affinity ligand for human PPAR-gamma. The increased potency of GW1929 compared with troglitazone both in vitro and in vivo may translate into improved clinical efficacy when used as monotherapy in type 2 diabetic patients. In addition, the significant

  7. From obesity genetics to the future of personalized obesity therapy.

    PubMed

    El-Sayed Moustafa, Julia S; Froguel, Philippe

    2013-07-01

    Obesity is a disorder characterized by an excess accumulation of body fat resulting from a mismatch between energy intake and expenditure. Incidence of obesity has increased dramatically in the past few years, almost certainly fuelled by a shift in dietary habits owing to the widespread availability of low-cost, hypercaloric foods. However, clear differences exist in obesity susceptibility among individuals exposed to the same obesogenic environment, implicating genetic risk factors. Numerous genes have been shown to be involved in the development of monofactorial forms of obesity. In genome-wide association studies, a large number of common variants have been associated with adiposity levels, each accounting for only a small proportion of the predicted heritability. Although the small effect sizes of obesity variants identified in genome-wide association studies currently preclude their utility in clinical settings, screening for a number of monogenic obesity variants is now possible. Such regular screening will provide more informed prognoses and help in the identification of at-risk individuals who could benefit from early intervention, in evaluation of the outcomes of current obesity treatments, and in personalization of the clinical management of obesity. This Review summarizes current advances in obesity genetics and discusses the future of research in this field and the potential relevance to personalized obesity therapy.

  8. 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.

  9. Childhood obesity: causes and consequences

    PubMed Central

    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. PMID:25949965

  10. Juvenile Obesity, Physical Activity, and Lifestyle Changes.

    ERIC Educational Resources Information Center

    Bar-Or, Oded

    2000-01-01

    Because many obese children become obese adults, the recent rapid increase in juvenile obesity poses a major public health challenge. Enhanced physical activity is a cornerstone in a multidisciplinary approach to preventing and treating juvenile obesity. Giving exercise recommendations focused for obese youth is critical. Cutting down on sedentary…

  11. Normal Weight Obesity: A Hidden Health Risk?

    MedlinePlus

    Diseases and Conditions Obesity Can you be considered obese if you have a normal body weight? Answers from Katherine Zeratsky, R.D., L. ... considered obese — a condition known as normal weight obesity. Normal weight obesity means you may have the ...

  12. Endocannabinoids and obesity.

    PubMed

    Chen, Guoxun; Pang, Zhen

    2013-01-01

    A safe and effective antiobesity drug is needed to combat the global obesity epidemic. The discovery of cannabinoids from medicinal herbs has revealed the endocannabinoid system (ECS) in animals and humans, which regulates various physiological activities such as feeding, thermogenesis, and body weight (BW). Although cannabinoid receptors 1 (CB1) antagonists have shown antiobesity efficacies in animal models and in the clinic, they failed to establish as a treatment due to their psychological side effects. Recent studies indicate that CB1 in various peripheral tissues may mediate some of the therapeutic effects of CB1 antagonists, such as improved lipid and glucose homeostasis. It rationalizes the development of compounds with limited brain penetration, for minimizing the side effects while retaining the therapeutic efficacies. A survey of the literature has revealed some controversies about how the ECS affects obesity. This review summarizes the research progresses and discusses some future perspectives.

  13. Obesity and Breast Cancer.

    PubMed

    Fortner, Renée T; Katzke, Verena; Kühn, Tilman; Kaaks, Rudolf

    2016-01-01

    The relationship between adiposity and breast cancer risk and prognosis is complex, with associations that differ depending on when body size is assessed (e.g., pre- vs. postmenopausal obesity) and when breast cancer is diagnosed (i.e., pre- vs. postmenopausal disease). Further, the impact of obesity on risk differs by tumor hormone receptor status (e.g., estrogen (ER) and progesterone (PR) receptor) and, among postmenopausal women, use of exogenous hormones (i.e., hormone replacement therapy (HRT)). In the context of these complexities, this review focuses on associations between childhood and adolescent adiposity, general adiposity, weight changes (i.e., loss and gain), abdominal adiposity, and breast cancer risk and survival. Finally, we discuss potential mechanisms linking adiposity to breast cancer.

  14. Food Retailers and Obesity.

    PubMed

    Stanton, Rosemary A

    2015-03-01

    We live in an 'obesogenic environment' where we are constantly bombarded with choices that encourage us to move less and eat more. Many factors influence our dietary choices, including the expert marketers who advise manufacturers on ways to encourage the population to buy more, especially profitable, palatable 'ultra-processed' foods. Supermarkets themselves have become skilled in manipulating buying behaviour, using their layout and specific product placement as well as advertising to maximise purchases of particular foods. Increasingly, supermarkets push their own 'house' brands. Those marketing fast foods also use persuasive tactics to attract customers, especially children who they entice with non-food items such as promotional or collectable toys. There is no mystery to the increase in obesity: our energy intake from foods and drinks has increased over the same period that energy output has decreased. Obesity has a range of relevant factors, but there is little doubt that marketing from supermarkets and fast food retailers has played a role.

  15. Obesity: An Immunometabolic Perspective

    PubMed Central

    Ray, Indrani; Mahata, Sushil K.; De, Rajat K.

    2016-01-01

    Obesity, characterized by chronic activation of inflammatory pathways, is a critical factor contributing to insulin resistance (IR) and type 2 diabetes (T2D). Free fatty acids (FFAs) are increased in obesity and are implicated as proximate causes of IR and induction of inflammatory signaling in adipose, liver, muscle, and pancreas. Cells of the innate immune system produce cytokines, and other factors that affect insulin signaling and result in the development of IR. In the lean state, adipose tissue is populated by adipose tissue macrophage of the anti-inflammatory M2 type (ATM2) and natural killer (NK) cells; this maintains the insulin-sensitive phenotype because ATM2 cells secrete IL10. In contrast, obesity induces lipolysis and release of pro-inflammatory FFAs and factors, such as chemokine (C–C motif) ligand 2 (CCL2) and tumor necrosis factor alpha (TNF-α), which recruit blood monocytes in adipose tissue, where they are converted to macrophages of the highly pro-inflammatory M1-type (ATM1). Activated ATM1 produce large amounts of pro-inflammatory mediators such as TNF-α, interleukin-1β, IL-6, leukotriene B4, nitric oxide (NO), and resistin that work in a paracrine fashion and cause IR in adipose tissue. In the liver, both pro-inflammatory Kupffer cells (M1-KCs) and recruited hepatic macrophages (Ly6Chigh) contribute to decreased hepatic insulin sensitivity. The present mini-review will update the bidirectional interaction between the immune system and obesity-induced changes in metabolism in adipose tissue and liver and the metabolic consequences thereof. PMID:28018292

  16. [The energetics of obesity].

    PubMed

    Bergouignan, Audrey; Blanc, Stéphane

    2006-01-01

    Although there is little argument about the state of energy imbalance that produces weight gain, there is considerable argument about the respective role of genetics, diet and physical activity in achieving obesity. In the USA, obesity has increased in the last decades despite a concomitant decrease in total energy and fat intake suggesting that there has been a dramatic drop in total energy expenditure. In this review, we investigated the respective role of resting metabolic rate, post-prandial thermogenesis, and activity energy expenditure in this lower energy output, and provided evidence that physical inactivity is the major contributor. Based on Jean Mayer original observation (Mayer et al., 1954), we hypothesize that there is a level of physical activity below which mechanisms of body mass regulation are impaired. The increasing prevalence of obesity may reflect the fact the majority of the population has fallen below such a level of physical activity. However, a causal relation between physical inactivity and obesity is still difficult to prove, probably because of the lack of longitudinal models to investigate the physiological consequences of inactivity and because the deleterious consequences of sedentary behaviors are essentially deduced from the benefits of exercise training. By using long term strict bed rest as a unique model of inactivity, we provide evidence that inactivity per se indeed disrupts fuel homeostasis and partitions post-absorptive and post-prandial fat use towards storage, thus promoting weight gain in the long term. More research is needed to investigate mechanisms and to determine the minimal physical activity our body has been engineered for by evolution.

  17. Diagnostic imaging in obesity.

    PubMed

    Machann, Jürgen; Horstmann, Annette; Born, Mark; Hesse, Swen; Hirsch, Franz Wolfgang

    2013-04-01

    Magnetic resonance of the body offers different techniques for mapping fat deposits (MR Imaging) and analysis of organs with small amounts of lipids (MR Spectroscopy). Possible approaches for whole-body assessment of adipose tissue are presented and discussed and spectroscopic examinations in different organs are depicted. With magnetic resonance imaging (MRI) it has been shown that obesity per se is not a marker for metabolic failure, but depends on regional variations of body composition and ectopic lipid accumulation. In addition MRI of the brain is a powerful research tool to understand the brain's role in the development and maintenance of obesity and the overconsumption of foods in obese individuals. Sonography has a low accuracy in estimating hepatic steatosis until now. New sonographic methods have been evaluated to detect hepatic steatosis by physical properties of fatty tissue as tissue stiffness, sound absorption or sound speed. Nuclear medicine and in particular Positron Emission Tomography (PET) methods are used to explore central pathophysiology, brown adipose tissue activity and alterations in homeostatic feedback and gut-brain communication.

  18. [Carbohydrate sweeteners and obesity].

    PubMed

    Wystrychowski, Grzegorz; Zukowska-Szczechowska, Ewa; Obuchowicz, Ewa; Grzeszczak, Władysław; Wystrychowski, Antoni

    2012-01-01

    The U.S. prevalence of obesity increases since the mid-70s of the 20th century. Around that time high-fructose corn syrup (HFCS)--mixture of fructose and glucose was introduced as a sweetener replacing sucrose in the food production. HFCS containing 55% fructose and 42-45% glucose (HFCS55) has dominated the American soft drink industry and HFCS has recently become commonly used in Poland. The coincidence of HFCS introduction and obesity epidemic raised widely publicized suspicions of a causal relationship between the two. As a possible mechanism, a higher content of fructose in the HFCS55, as compared with sucrose was suggested -fructose is known to increase serum uric acid level, induce hepatic lipogenesis and not stimulate postprandial hyperinsulinemia, a main activator of leptin release. Few comparative studies of HFCS and sucrose have largely failed to reveal any different impacts on the metabolic parameters, yet they were mainly short-term. It has been recently shown that obesity is linked with changes in the intenstinal flora. Among the causes of allegedly different effects of sucrose and HFCS on metabolism, their influence on the gut microbiome has not been examined. Some bacterial types do not hydrolyze sucrose which may determine different compositions of gut flora with the use of both sweeteners. Studies involving quantitative analysis of bacterial DNA in the stool, both in animals and in humans, shall shed light on the issue that has recently so much absorbed the U.S. public opinion.

  19. [Pharmacological therapy of obesity].

    PubMed

    Pagotto, Uberto; Vanuzzo, Diego; Vicennati, Valentina; Pasquali, Renato

    2008-04-01

    Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and

  20. Pediatric obesity. An introduction ☆

    PubMed Central

    Yanovski, Jack A.

    2015-01-01

    The prevalence of child and adolescent obesity in the United States increased dramatically between 1970 and 2000, and there are few indications that the rates of childhood obesity are decreasing. Obesity is associated with myriad medical, psychological, and neurocognitive abnormalities that impact children’s health and quality of life. Genotypic variation is important in determining the susceptibility of individual children to undue gains in adiposity; however, the rapid increase in pediatric obesity prevalence suggests that changes to children’s environments and/or to their learned behaviors may dramatically affect body weight regulation. This paper presents an overview of the epidemiology, consequences, and etiopathogenesis of pediatric obesity, serving as a general introduction to the subsequent papers in this Special Issue that address aspects of childhood obesity and cognition in detail. PMID:25836737

  1. Factors contributing to adolescent obesity.

    PubMed

    Al-Kloub, Manal I; Froelicher, Erika S

    2009-06-01

    Obesity in children is a significant public health concern. The prevalence of overweight and obesity in Jordanian children, and adolescents has increased in the last decade. The consequences of obesity to health in childhood and adulthood have both medical, and economic cost to individuals and society. This paper reviews the factors that contribute to adolescent obesity and emphasizes behavioral and environmental factors. An individual's behaviors such as increased consumption of high caloric foods, increased sedentary activity while decreasing physical activity has been identified as key issues in the development of obesity. Additionally, the current environment in homes, schools, and neighborhoods tend to discourage a healthy lifestyle. A comprehensive approach that involves the whole community is the best strategy for preventing adolescent obesity. Nurses are in a unique position to provide leadership in developing programs for healthier lifestyle choices for adolescents' and adoption of these goals into their daily lives.

  2. Obesity and pelvic floor dysfunction.

    PubMed

    Ramalingam, Kalaivani; Monga, Ash

    2015-05-01

    Obesity is associated with a high prevalence of pelvic floor disorders. Patients with obesity present with a range of urinary, bowel and sexual dysfunction problems as well as uterovaginal prolapse. Urinary incontinence, faecal incontinence and sexual dysfunction are more prevalent in patients with obesity. Uterovaginal prolapse is also more common than in the non-obese population. Weight loss by surgical and non-surgical methods plays a major role in the improvement of these symptoms in such patients. The treatment of symptoms leads to an improvement in their quality of life. However, surgical treatment of these symptoms may be accompanied by an increased risk of complications in obese patients. A better understanding of the mechanism of obesity-associated pelvic floor dysfunction is essential.

  3. A case of pantaloon obesity.

    PubMed

    Leonidas, J R; Hyppolite, N

    1983-06-01

    A 79-year-old woman presented with an unusual form of obesity limited to the lower half of the body from the waistline down but sparing the lower legs and feet. The patient was massive (360 lbs) and symmetrical. The superior half of the body was normal with no morbid obesity or lipoatrophy. These findings do not correspond to any classic form of lipodystrophy. The fat distribution is reminiscent of a pair of knickers and qualifies for the name "pantaloon obesity."

  4. Obesity: A National Security Concern

    DTIC Science & Technology

    2011-02-28

    live shorter lives than their parents.”6 The study also included an ironic conclusion that one of the contributing factors to childhood obesity is a...accessed September 10, 2010). 7 Christenson, Too Fat to Fight, 1. 8 Nikhil Swaminathan, “Is School Lunch Contributing to Childhood Obesity ?,” March...18, 2010, http://www.good.is/post/is-school-lunch-contributing-to- childhood - obesity /r (accessed January 17, 2011). 9 Katherine M. Flegal

  5. Obesity: A Perspective from Hypertension.

    PubMed

    Susic, Dinko; Varagic, Jasmina

    2017-01-01

    The prevalence of obesity-related hypertension is high worldwide and has become a major health issue. The mechanisms by which obesity relates to hypertensive disease are still under intense research scrutiny, and include altered hemodynamics, impaired sodium homeostasis, renal dysfunction, autonomic nervous system imbalance, endocrine alterations, oxidative stress and inflammation, and vascular injury. Most of these contributing factors interact with each other at multiple levels. Thus, as a multifactorial and complex disease, obesity-related hypertension should be recognized as a distinctive form of hypertension, and specific considerations should apply in planning therapeutic approaches to treat obese individuals with high blood pressure.

  6. Pregnancy and Obesity: Know the Risks

    MedlinePlus

    ... Pregnancy week by week Concerned about pregnancy and obesity? Understand the risks of obesity during pregnancy — plus steps to promote a healthy ... you can do to promote a healthy pregnancy. Obesity is defined as having an excessive amount of ...

  7. 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.

  8. Perceived weight discrimination and obesity.

    PubMed

    Sutin, Angelina R; Terracciano, Antonio

    2013-01-01

    Weight discrimination is prevalent in American society. Although associated consistently with psychological and economic outcomes, less is known about whether weight discrimination is associated with longitudinal changes in obesity. The objectives of this research are (1) to test whether weight discrimination is associated with risk of becoming obese (Body Mass Index≥30; BMI) by follow-up among those not obese at baseline, and (2) to test whether weight discrimination is associated with risk of remaining obese at follow-up among those already obese at baseline. Participants were drawn from the Health and Retirement Study, a nationally representative longitudinal survey of community-dwelling US residents. A total of 6,157 participants (58.6% female) completed the discrimination measure and had weight and height available from the 2006 and 2010 assessments. Participants who experienced weight discrimination were approximately 2.5 times more likely to become obese by follow-up (OR = 2.54, 95% CI = 1.58-4.08) and participants who were obese at baseline were three times more likely to remain obese at follow up (OR = 3.20, 95% CI = 2.06-4.97) than those who had not experienced such discrimination. These effects held when controlling for demographic factors (age, sex, ethnicity, education) and when baseline BMI was included as a covariate. These effects were also specific to weight discrimination; other forms of discrimination (e.g., sex, race) were unrelated to risk of obesity at follow-up. The present research demonstrates that, in addition to poorer mental health outcomes, weight discrimination has implications for obesity. Rather than motivating individuals to lose weight, weight discrimination increases risk for obesity.

  9. Endothelial dysfunction in morbid obesity.

    PubMed

    Mauricio, Maria Dolores; Aldasoro, Martin; Ortega, Joaquin; Vila, José María

    2013-01-01

    Morbid obesity is a chronic multifunctional disease characterized by an accumulation of fat. Epidemiological studies have shown that obesity is associated with cardiovascular and metabolic disorders. Endothelial dysfunction, as defined by an imbalance between relaxing and contractile endothelial factors, plays a central role in the pathogenesis of these cardiometabolic diseases. Diminished bioavailability of nitric oxide (NO) contributes to endothelial dysfunction and impairs endothelium- dependent vasodilatation. But this is not the only mechanism that drives to endothelial dysfunction. Obesity has been associated with a chronic inflammatory process, atherosclerosis, and oxidative stress. Moreover levels of asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), are elevated in obesity. On the other hand, increasing prostanoid-dependent vasoconstriction and decreasing vasodilator prostanoids also lead to endothelial dysfunction in obesity. Other mechanisms related to endothelin-1 (ET-1) or endothelium derived hyperpolarizing factor (EDHF) have been proposed. Bariatric surgery (BS) is a safe and effective means to achieve significant weight loss, but its use is limited only to patients with severe obesity including morbid obesity. BS also proved efficient in endothelial dysfunction reduction improving cardiovascular and metabolic comorbidities associated with morbid obesity such as diabetes, coronary artery disease, nonalcoholic fatty liver disease and cancer. This review will provide a brief overview of the mechanisms that link obesity with endothelial dysfunction, and how weight loss is a cornerstone treatment for cardiovascular comorbidities obesity-related. A better understanding of the mechanisms of obesity-induced endothelial dysfunction may help develop new therapeutic strategies to reduce cardiovascular morbidity and mortality.

  10. Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism

    PubMed Central

    Thanos, PK; Michaelides, M; Gispert, J-D; Pascau, J; Soto-Montenegro, ML; Desco, M; Wang, R; Wang, G-J; Volkow, ND

    2009-01-01

    Objective Food intake is regulated by factors that modulate caloric requirements as well as food’s reinforcing properties. In this study, we measured brain glucose utilization to an olfactory stimulus (bacon scent), and we examined the role of food restriction and genetic predisposition to obesity on such brain metabolic activity. Methods Zucker obese (Ob) and lean (Le) rats were divided into four groups: (1) Ob ad-libitum fed, (2) Ob food restricted (70% of ad libitum), (3) Le ad-libitum fed and (4) Le food restricted. Rats were scanned using µ-positron emission tomography and 2-[18F]-fluoro-2-deoxy-d-glucose under two conditions: (1) baseline scan (no stimulation) and (2) challenge scan (food stimulation, FS). Results FS resulted in deactivation of the right and left hippocampus. Ob rats showed greater changes with FS than Le rats (deactivation of hippocampus and activation of the medial thalamus) and Ob but not Le animals deactivated the frontal cortex and activated the superior colliculus. Access to food resulted in an opposite pattern of metabolic changes to the food stimuli in olfactory nucleus (deactivated in unrestricted and activated in restricted) and in right insular/parietal cortex (activated in unrestricted and deactivated in restricted). In addition, restricted but not unrestricted animals activated the medial thalamus. Conclusions The greater changes in the Ob rats suggest that leptin modulates the regional brain responses to a familiar food stimulus. Similarly, the differences in the pattern of responses with food restriction suggest that FS is influenced by access to food conditions. The main changes with FS occurred in the hippocampus, a region involved in memory, the insular cortex, a region involved with interoception (perception of internal sensations), the medial thalamus (region involved in alertness) and in regions involved with sensory perception (olfactory bulb, olfactory nucleus, occipital cortex, superior colliculus and parietal

  11. The effect of obesity surgery on obesity comorbidity.

    PubMed

    Bouldin, Marshall J; Ross, Leigh Ann; Sumrall, Caryl D; Loustalot, Fleetwood V; Low, Annette K; Land, Kelly K

    2006-04-01

    Obesity is epidemic in the modern world. It is becoming increasingly clear that obesity is a major cause of cardiovascular disease, diabetes, and renal disease, as well as a host of other comorbidities. There are at present no generally effective long-term medical therapies for obesity. Surgical therapy for morbid obesity is not only effective in producing long-term weight loss but is also effective in ameliorating or resolving several of the most significant complications of obesity, including diabetes, hypertension, dyslipidemia, sleep apnea, gastroesophageal reflux disease, degenerative joint disease, venous stasis, pseudotumor cerebri, nonalcoholic steatohepatitis, urinary incontinence, fertility problems, and others. The degree of benefit and the rates of morbidity and mortality of the various surgical procedures vary according to the procedure.

  12. Methylglyoxal, obesity, and diabetes.

    PubMed

    Matafome, Paulo; Sena, Cristina; Seiça, Raquel

    2013-06-01

    Methylglyoxal (MG) is a highly reactive compound derived mainly from glucose and fructose metabolism. This metabolite has been implicated in diabetic complications as it is a strong AGE precursor. Furthermore, recent studies suggested a role for MG in insulin resistance and beta-cell dysfunction. Although several drugs have been developed in the recent years to scavenge MG and inhibit AGE formation, we are still far from having an effective strategy to prevent MG-induced mechanisms. This review summarizes the mechanisms of MG formation, detoxification, and action. Furthermore, we review the current knowledge about its implication on the pathophysiology and complications of obesity and diabetes.

  13. [Obesity, migration and adolescence].

    PubMed

    Chamay-Weber, Catherine; Shehu-Brovina, Shqipe; Narring, Françoise

    2012-06-13

    Weight management interventions during adolescence are challenging. Migration adds complexity to this problem, making migrant families more vulnerable. Teenagers confront families to new values transmitted by the host society: opulence, junk food, video games. Obesity should not be seen as a single issue of calories-excess, but must be considered as being part of a larger problem, which takes into account the context of the familial and societal life of the migrants. The caregivers must have an overall view of the situation to provide appropriate approaches to weight management.

  14. The Educational Aspects of Obesity.

    ERIC Educational Resources Information Center

    Kaufmann, David A.

    A traditional discussion of obesity considers the number of pounds over what is considered average for one's age, height, and sex, and is based on the assumption that the average weight for a given group of people of the same age, height, and sex is the healthiest status for that group. There is a physiological and biochemical basis for obesity.…

  15. Sociological Factors Affecting Childhood Obesity

    ERIC Educational Resources Information Center

    Forster-Scott, Latisha

    2007-01-01

    According to data from the National Center for Health Statistics, childhood obesity rates are highest among ethnic minorities. It is very helpful to consider the role of culture when attempting to analyze and explain obesity rates in ethnic minority populations. Culture influences the attitudes and beliefs toward exercise, food and nutrition, and…

  16. Overweight and Obesity. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2005-01-01

    In this world of receiving immediate gratification, being over scheduled, and having access to a myriad of technology, poor nutrition and lack of daily physical activity are two of the results. "Obesity is a silent epidemic," former U.S. Surgeon General David Satcher stated in 2002 (Healthy schools summit weighs in on obesity). Due to the demands…

  17. Management of obesity in pregnancy.

    PubMed

    Catalano, Patrick M

    2007-02-01

    Maternal pregravid obesity is a significant risk factor for adverse outcomes during pregnancy. In early pregnancy there is an increased risk of spontaneous abortion and congenital anomalies. In later gestation maternal metabolic manifestations of the metabolic syndrome, such as gestational hypertensive disorders and diabetes, become clinically recognized because of the increased insulin resistance in obese compared with nonobese women. In women with pregestational glucose intolerance, hypertension, central obesity, and lipid disorders, the physiologic changes in pregnancy increase the risk of problems previously not routinely encountered during pregnancy. These include chronic cardiac dysfunction, proteinuria, sleep apnea, and nonalcoholic fatty liver disease. At parturition the obese patient is at an increased risk of cesarean delivery and associated complications of anesthesia, wound disruption, infection, and deep venous thrombophlebitis. For the fetus there are short-term risks of fetal macrosomia, more specifically obesity, and long-term risks of adolescent components of the metabolic syndrome. Although preliminary results of bariatric surgery are encouraging, the procedure is expensive and not for all obese women, and we recognize that long-term follow-up data on offspring of obese women who have undergone bariatric surgery before pregnancy are lacking. In the interim, we need to encourage obese women to lose weight before conception, using lifestyle changes if possible. During pregnancy, weight gain should be limited to Institute of Medicine guidelines (currently under review) and encouragement given for physical activity.

  18. Childhood Obesity and Academic Outcomes

    ERIC Educational Resources Information Center

    James B. Hunt Jr. Institute for Educational Leadership and Policy, 2008

    2008-01-01

    Childhood obesity is on the rise across the country and in North Carolina, with four times as many children exhibiting signs of obesity now as they did 20 years ago. The costs in terms of medical expenses are staggering, with one estimate putting the cost to North Carolina at $16 million a year. Some North Carolina legislators have expressed…

  19. Obesity, inflammation and endothelial dysfunction.

    PubMed

    Iantorno, M; Campia, U; Di Daniele, N; Nistico, S; Forleo, G B; Cardillo, C; Tesauro, M

    2014-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients.

  20. Obesity Gene Atlas in Mammals

    PubMed Central

    Kunej, Tanja; Jevsinek Skok, Dasa; Zorc, Minja; Ogrinc, Ana; Michal, Jennifer J.; Kovac, Milena; Jiang, Zhihua

    2013-01-01

    Obesity in humans has increased at an alarming rate over the past two decades and has become one of the leading public health problems worldwide. Studies have revealed a large number of genes/markers that are associated with obesity and/or obesity-related phenotypes, indicating an urgent need to develop a central database for helping the community understand the genetic complexity of obesity. In the present study, we collected a total of 1,736 obesity associated loci and created a freely available obesity database, including 1,515 protein-coding genes and 221 microRNAs (miRNAs) collected from four mammalian species: human, cattle, rat, and mouse. These loci were integrated as orthologs on comparative genomic views in human, cattle, and mouse. The database and genomic views are freely available online at: http://www.integratomics-time.com/fat_deposition. Bioinformatics analyses of the collected data revealed some potential novel obesity related molecular markers which represent focal points for testing more targeted hypotheses and designing experiments for further studies. We believe that this centralized database on obesity and adipogenesis will facilitate development of comparative systems biology approaches to address this important health issue in human and their potential applications in animals. PMID:25031655

  1. [Obesity: stigmatization, discrimination, body image].

    PubMed

    Kinzl, Johann F

    2016-03-01

    Obesity is a heterogeneous condition with multifactorial genesis (genetic predisposition, life-style, psychosocial situation), but there is a relatively homogeneous negative stereotype of obese individuals, because overweight and obesity are seen as self-inflicted disorders caused by physical inactivity and disorderd eating behavior. Obese individuals are confronted with far-reaching stigmatization and discrimination. Typical stereotypes are laziness, unattractiveness, work refusal. This negative image by the environment contributes to negative self-awareness and self-stigmatization, accompanied by a poor self-esteem and feelings of poor self-control and reduced self-efficacy, resulting in poor constructive coping strategies for overweight reduction. In addition, a disturbed body image combined with deep dissatisfaction with their own body is often found in many obese individuals. There is not always a close connection between body weight and body dissatisfaction. Young women and individuals with a binge eating disorder often show an increased body dissatisfaction as well.

  2. The Genetics of Pediatric Obesity

    PubMed Central

    Chesi, Alessandra; Grant, Struan F. A.

    2015-01-01

    Obesity among children and adults has notably escalated over recent decades and represents a global major health problem. We now know that both genetics and environmental factors contribute to its complex etiology. Genome-wide association studies (GWAS) have revealed compelling genetic signals influencing obesity risk in adults. Recent reports for childhood obesity revealed that many adult loci also play a role in the pediatric setting. Childhood GWAS have uncovered novel loci below the detection range in adult studies, suggesting that obesity genes may be more easily uncovered in the pediatric setting. Shedding light on the genetic architecture of childhood obesity will facilitate prevention and treatment of pediatric cases and will have fundamental implications for diseases that present later in life. PMID:26439977

  3. Maternal obesity and prenatal programming.

    PubMed

    Elshenawy, Summer; Simmons, Rebecca

    2016-11-05

    Obesity is a significant and increasing public health concern in the United States and worldwide. Clinical and epidemiological evidence clearly shows that genetic and environmental factors contribute to the increased susceptibility of humans to obesity and its associated comorbidities; the interplay of these factors is explained by the concept of epigenetics. The impact of maternal obesity goes beyond the newborn period; fetal programming during the critical window of pregnancy, can have long term detrimental effects on the offspring as well as future generations. Emerging evidence is uncovering a link between the clinical and molecular findings in the offspring with epigenetic changes in the setting of maternal obesity. Research targeted towards reducing the transgenerational propagation and developmental programming of obesity is vital in reducing the increasing rates of disease.

  4. Endothelin-1 contributes to endothelial dysfunction and enhanced vasoconstriction through augmented superoxide production in penile arteries from insulin-resistant obese rats: role of ETA and ETB receptors

    PubMed Central

    Sánchez, A; Martínez, P; Muñoz, M; Benedito, S; García-Sacristán, A; Hernández, M; Prieto, D

    2014-01-01

    Background and Purpose We assessed whether endothelin-1 (ET-1) inhibits NO and contributes to endothelial dysfunction in penile arteries in a model of insulin resistance-associated erectile dysfunction (ED). Experimental Approach Vascular function was assessed in penile arteries, from obese (OZR) and lean (LZR) Zucker rats, mounted in microvascular myographs. Changes in basal and stimulated levels of superoxide (O2−) were detected by lucigenin-enhanced chemiluminescence and ET receptor expression was determined by immunohistochemistry. Key Results ET-1 stimulated acute O2− production that was blunted by tempol and the NADPH oxidase inhibitor, apocynin, but markedly enhanced in obese animals. ET-1 inhibited the vasorelaxant effects of ACh and of the NO donor S-nitroso-N-acetyl-DL-penicillamine in arteries from both LZR and OZR. Selective ETA (BQ123) or ETB receptor (BQ788) antagonists reduced both basal and ET-1-stimulated superoxide generation and reversed ET-1-induced inhibition of NO-mediated relaxations in OZR, while only BQ-123 antagonized ET-1 actions in LZR. ET-1-induced vasoconstriction was markedly enhanced by NO synthase blockade and reduced by endothelium removal and apocynin. In endothelium-denuded penile arteries, apocynin blunted augmented ET-1-induced contractions in OZR. Both ETA and ETB receptors were expressed in smooth muscle and the endothelial layer and up-regulated in arteries from OZR. Conclusions and Implications ET-1 stimulates ETA-mediated NADPH oxidase-dependent ROS generation, which inhibits endothelial NO bioavailability and contributes to ET-1-induced contraction in healthy penile arteries. Enhanced vascular expression of ETB receptors contributes to augmented ROS production, endothelial dysfunction and increased vasoconstriction in erectile tissue from insulin-resistant obese rats. Hence, antagonism of ETB receptors might improve the ED associated with insulin-resistant states. PMID:25091502

  5. Regular tart cherry intake alters abdominal adiposity, adipose gene transcription, and inflammation in obesity-prone rats fed a high fat diet.

    PubMed

    Seymour, E M; Lewis, Sarah K; Urcuyo-Llanes, Daniel E; Tanone, Ignasia I; Kirakosyan, Ara; Kaufman, Peter B; Bolling, Steven F

    2009-10-01

    Obesity, systemic inflammation, and hyperlipidemia are among the components of metabolic syndrome, a spectrum of phenotypes that can precede the development of type 2 diabetes and cardiovascular disease. Animal studies show that intake of anthocyanin-rich extracts can affect these phenotypes. Anthocyanins can alter the activity of tissue peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism and inflammation. However, it is unknown if physiologically relevant, anthocyanin-containing whole foods confer similar effects to concentrated, anthocyanin extracts. The effect of anthocyanin-rich tart cherries was tested in the Zucker fatty rat model of obesity and metabolic syndrome. For 90 days, rats were pair-fed a higher fat diet supplemented with either 1% (wt/wt) freeze-dried, whole tart cherry powder or with a calorie- and macronutrient-matched control diet. Tart cherry intake was associated with reduced hyperlipidemia, percentage fat mass, abdominal fat (retroperitoneal) weight, retroperitoneal interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) expression, and plasma IL-6 and TNF-alpha. Tart cherry diet also increased retroperitoneal fat PPAR-alpha and PPAR-gamma mRNA (P = .12), decreased IL-6 and TNF-alpha mRNA, and decreased nuclear factor kappaB activity. In conclusion, in at-risk obese rats fed a high fat diet, physiologically relevant tart cherry consumption reduced several phenotypes of metabolic syndrome and reduced both systemic and local inflammation. Tart cherries may reduce the degree or trajectory of metabolic syndrome, thereby reducing risk for the development of type 2 diabetes and heart disease.

  6. Endoprosthesis and Obesity

    PubMed Central

    Grubor, Predrag; Manojlovic, Slavko; Manojlovic, Nemanja; Grubor, Milan

    2013-01-01

    ABSTRACT Introduction: Obesity represents a significant risk factor in the pathophysiology of degenerative changes in coxarthrosis. Objective: The study aims to investigate obesity as a risk factor in the examined sample comprising 136 patients who underwent hip endoprothesis implantation. Material and methods: The series comprised 136 patients with a hip endoprosthesis implanted, where the patients’ BMI, amount of blood used, duration of surgery, number of assistants, and type of anaesthesia were observed. Wounds and late post-operative complications, infections, haemorrhage, vein thrombosis, endoprosthesis dislocations, length of inpatient stay, start of physical therapy and full weight-bearing were also observed. The observation period lasted six months on average. Discussion: In simple terms, the three greatest factors when implanting a hip endoprosthesis are as follows: properties of the endoprosthesis, the orthopaedic surgeon’s skill and experience, and individual characteristics of the patient, i.e. age, sex, health condition, body weight, BMI, adequate physical therapy. Conclusion: We believe that the implantation of a hip endoprosthesis should be postponed for patients with a BMI exceeding 29.99. Such patients should receive endocrine treatment, they should undergo a weight loss programme in order to reduce their body weight and in order to reduce their BMI to under 29.99. PMID:25568519

  7. 11β-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus.

    PubMed

    Pereira, C D; Azevedo, I; Monteiro, R; Martins, M J

    2012-10-01

    Recent evidence strongly argues for a pathogenic role of glucocorticoids and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in obesity and the metabolic syndrome, a cluster of risk factors for atherosclerotic cardiovascular disease and type 2 diabetes mellitus (T2DM) that includes insulin resistance (IR), dyslipidaemia, hypertension and visceral obesity. This has been partially prompted not only by the striking clinical resemblances between the metabolic syndrome and Cushing's syndrome (a state characterized by hypercortisolism that associates with metabolic syndrome components) but also from monogenic rodent models for the metabolic syndrome (e.g. the leptin-deficient ob/ob mouse or the leptin-resistant Zucker rat) that display overall increased secretion of glucocorticoids. However, systemic circulating glucocorticoids are not elevated in obese patients and/or patients with metabolic syndrome. The study of the role of 11β-HSD system shed light on this conundrum, showing that local glucocorticoids are finely regulated in a tissue-specific manner at the pre-receptor level. The system comprises two microsomal enzymes that either activate cortisone to cortisol (11β-HSD1) or inactivate cortisol to cortisone (11β-HSD2). Transgenic rodent models, knockout (KO) for HSD11B1 or with HSD11B1 or HSD11B2 overexpression, specifically targeted to the liver or adipose tissue, have been developed and helped unravel the currently undisputable role of the enzymes in metabolic syndrome pathophysiology, in each of its isolated components and in their prevention. In the transgenic HSD11B1 overexpressing models, different features of the metabolic syndrome and obesity are replicated. HSD11B1 gene deficiency or HSD11B2 gene overexpression associates with improvements in the metabolic profile. In face of these demonstrations, research efforts are now being turned both into the inhibition of 11β-HSD1 as a possible pharmacological target and into the role of dietary habits on the

  8. Treating Child Obesity and Associated Medical Conditions

    ERIC Educational Resources Information Center

    Caprio, Sonia

    2006-01-01

    With American children on course to grow into the most obese generation of adults in history, Sonia Caprio argues that it is critical to develop more effective strategies for preventing childhood obesity and treating serious obesity-related health complications. She notes that although pediatricians are concerned about the obesity problem, most…

  9. Splanchnic lipolysis in human obesity

    PubMed Central

    Nielsen, Soren; Guo, ZengKui; Johnson, C. Michael; Hensrud, Donald D.; Jensen, Michael D.

    2004-01-01

    Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men. PMID:15173884

  10. Deep Brain Stimulation for Obesity

    PubMed Central

    Sussman, Eric S; Zhang, Michael; Pendharkar, Arjun V; Azagury, Dan E; Bohon, Cara; Halpern, Casey H

    2015-01-01

    Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer’s disease, and depression and obsessive-compulsive disorder have demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain. PMID:26180683

  11. Maternal Obesity and Neck Circumference.

    PubMed

    Anglim, B; O'Higgins, A; Daly, N; Farren, M; Turner, M J

    2015-06-01

    Obese women are more likely to require general anaesthesia for an obstetric intervention than non-obese. Difficult tracheal intubation and oxygen desaturation is more common in pregnancy. Failed tracheal intubation has been associated with an increase in neck circumference (NC). We studied the relationship between maternal obesity and NC as pregnancy advanced in women attending a standard antenatal clinic. Of the 96 women recruited, 13.5% were obese. The mean NC was 36.8cm (SD 1.9) in the obese women compared with 31.5cm (SD 1.6) in women with a normal BMI (p < 0.001) at 18-22 weeks gestation. In the obese women it increased on average by 1.5cm by 36-40 weeks compared with an increase of 1.6 cm in women with a normal BMI. The antenatal measurement of NC is a simple, inexpensive tool that is potentially useful for screening obese women who may benefit from an antenatal anaesthetic assessment.

  12. Preclinical models for obesity research.

    PubMed

    Barrett, Perry; Mercer, Julian G; Morgan, Peter J

    2016-11-01

    A multi-dimensional strategy to tackle the global obesity epidemic requires an in-depth understanding of the mechanisms that underlie this complex condition. Much of the current mechanistic knowledge has arisen from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. These experimental models mimic certain aspects of the human condition and its root causes, particularly the over-consumption of calories and unbalanced diets. As with human obesity, obesity in rodents is the result of complex gene-environment interactions. Here, we review the traditional monogenic models of obesity, their contemporary optogenetic and chemogenetic successors, and the use of dietary manipulations and meal-feeding regimes to recapitulate the complexity of human obesity. We critically appraise the strengths and weaknesses of these different models to explore the underlying mechanisms, including the neural circuits that drive behaviours such as appetite control. We also discuss the use of these models for testing and screening anti-obesity drugs, beneficial bio-actives, and nutritional strategies, with the goal of ultimately translating these findings for the treatment of human obesity.

  13. Preclinical models for obesity research

    PubMed Central

    Barrett, Perry; Morgan, Peter J.

    2016-01-01

    ABSTRACT A multi-dimensional strategy to tackle the global obesity epidemic requires an in-depth understanding of the mechanisms that underlie this complex condition. Much of the current mechanistic knowledge has arisen from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. These experimental models mimic certain aspects of the human condition and its root causes, particularly the over-consumption of calories and unbalanced diets. As with human obesity, obesity in rodents is the result of complex gene–environment interactions. Here, we review the traditional monogenic models of obesity, their contemporary optogenetic and chemogenetic successors, and the use of dietary manipulations and meal-feeding regimes to recapitulate the complexity of human obesity. We critically appraise the strengths and weaknesses of these different models to explore the underlying mechanisms, including the neural circuits that drive behaviours such as appetite control. We also discuss the use of these models for testing and screening anti-obesity drugs, beneficial bio-actives, and nutritional strategies, with the goal of ultimately translating these findings for the treatment of human obesity. PMID:27821603

  14. Prevalence of obesity in Malta

    PubMed Central

    Vassallo, J.; Calleja, N.; Camilleri, R.; Borg, A.; Bonnici, G.; Zhang, Y.; Pace, N.; Mamo, J.

    2016-01-01

    Summary Background Obesity is a global epidemic with the Mediterranean island of Malta being no exception. The World Health Organization (WHO) has identified Malta as one of the European countries with the highest obesity prevalence. Method A cross‐sectional study was conducted (2014–2016) under the auspices of the University of Malta. The prevalence of overweight‐obesity in Malta was calculated and then age stratified for comparisons with previous studies. Results The study identified 69.75% (95% CI: 68.32–71.18) of the Maltese population to be either overweight or obese. The men overweight/obese prevalence (76.28% 95% CI: 74.41–78.14) was statistically higher than that for women (63.06% 95% CI: 60.92–65.20) (p = 0.0001). Age stratification revealed that both genders had the highest overweight prevalence rates between 55 and 64 years (Men = 23.25% 95% CI: 20.43–26.33; Women = 24.68% 95% CI: 21.44–28.22). Men obesity prevalence rates were highest in the 35 to 44 years group (22.52% 95% CI: 19.65–25.68) while for women it was highest in the 55 to 64 years group (28.90%, 95% CI: 25.44–30.63). Conclusion Over a 35‐year period, an overall decrease in the normal and overweight BMI categories occurred with an increase in the prevalence of obesity. An exception was observed in the women, where the prevalence of normal BMI increased over this time period. Also, it appears that while the total population obesity prevalence increased (for 2016), a percentage of the women have shifted from an obese to an overweight status. PMID:28090352

  15. Obesity: genetic, molecular, and environmental aspects.

    PubMed

    Barness, Lewis A; Opitz, John M; Gilbert-Barness, Enid

    2007-12-15

    Obesity has emerged as one of the most serious public health concerns in the 21st century. Obese children tend to become obese adults. The dramatic rise in pediatric obesity closely parallels the rapid increase in the prevalence of adult obesity. As overweight children become adults they face the multitude of health problems associated with obesity at younger ages. The morbidity and mortality associated with obesity continue to increase. Obesity is one of the leading causes of preventable death. Complications of obesity include cardiovascular risks, hypertension, dyslipidemia, endothelial dysfunction, type 2 diabetes mellitus and impaired glucose tolerance, acanthosis nigricans, hepatic steatosis, premature puberty, hypogonadism and polycystic ovary syndrome, obstructive sleep disorder, orthopedic complications, cholelithiasis and pseudotumor cerebri. Genetic and molecular and environmental factors play an important role in the assessment and management of obesity.

  16. Stable isotopes in obesity research.

    PubMed

    Dolnikowski, Gregory G; Marsh, Julian B; Das, Sai Krupa; Welty, Francine K

    2005-01-01

    Obesity is recognized as a major public health problem. Obesity is a multifactorial disease and is often associated with a wide range of comorbidities including hypertension, non-insulin dependent (Type II) diabetes mellitus, and cardiovascular disease, all of which contribute to morbidity and mortality. This review deals with stable isotope mass spectrometric methods and the application of stable isotopes to metabolic studies of obesity. Body composition and total energy expenditure (TEE) can be measured by mass spectrometry using stable isotope labeled water, and the metabolism of protein, lipid, and carbohydrate can be measured using appropriate labeled tracer molecules.

  17. Obesity, paternalism and fairness.

    PubMed

    Kniess, Johannes

    2015-11-01

    Many liberal theories are committed to the promotion of population health, and the principle of non-interference in individual life plans. Public health interventions often bring out a tension between these two values. In this paper, I examine this tension by assessing the justifiability of liberty-restricting policies in the field of obesity prevention. As I want to show, a 'soft' form of paternalism, which interferes with people's choices to safeguard their true interests, goes some way in justifying such policies, but it leaves unaddressed the problem of limiting the liberty of those whose true interest is in pursuing an unhealthy lifestyle. I argue that in this latter case, the key to reconcile the promotion of population health with the respect for individual liberty is distributive justice: when we cannot help those who care about their health without doing the same for those who do not, fairness will often require us to do so.

  18. [Nutrition--obesity].

    PubMed

    Giusti, V; Clarisse, M; Di Vetta, V

    2005-01-05

    The gastric pacemaker is a new obesity treatment, which pleases by its simplicity and obvious lack of complications on the nutritional level. Its long-term efficacy is however to be confirmed and the criterions of the patients' selection to be defined. The rimonabant is a selective antagonist of the cannabinoid CBI receptor, able to reduce the quantity of the total food intake, and especially the greasy one. The first results on the short term look promising. The multiplication of food pyramids is the consequence of the scientific knowledge development in the nutritional field. On this basis, new pyramids are adapted, depending on the therapeutic objectives (weight loss, cardiovascular risk) and allowing either quantity or quality food. The taking charge of patients in group and according to the therapeutic education criterions makes easy a relation between the medical team and patients and allows these latters a better awareness of their disease and its long term treatment.

  19. 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.

  20. Sarcopenia and Visceral Obesity in Esophageal and Gastric Cancer

    ClinicalTrials.gov

    2017-02-17

    Esophageal Cancer; Gastric Cancer; Sarcopenia; Sarcopenic Obesity; Obesity; Visceral Obesity; Quality of Life; Surgery; Complication of Treatment; Chemotherapeutic Toxicity; Physical Activity; Oncology

  1. Childhood Obesity and Cognitive Achievement.

    PubMed

    Black, Nicole; Johnston, David W; Peeters, Anna

    2015-09-01

    Obese children tend to perform worse academically than normal-weight children. If poor cognitive achievement is truly a consequence of childhood obesity, this relationship has significant policy implications. Therefore, an important question is to what extent can this correlation be explained by other factors that jointly determine obesity and cognitive achievement in childhood? To answer this question, we exploit a rich longitudinal dataset of Australian children, which is linked to national assessments in math and literacy. Using a range of estimators, we find that obesity and body mass index are negatively related to cognitive achievement for boys but not girls. This effect cannot be explained by sociodemographic factors, past cognitive achievement or unobserved time-invariant characteristics and is robust to different measures of adiposity. Given the enormous importance of early human capital development for future well-being and prosperity, this negative effect for boys is concerning and warrants further investigation.

  2. [The social stigma of obesity].

    PubMed

    De Domingo Bartolomé, M; López Guzmán, José

    2014-01-01

    People who are overweight are at increased risk of certain chronic diseases and premature death. However, the physiological consequences are not limited to health symptoms and signs but transcend the social field. In fact, the stigma and discrimination faced by obese people has been proven in multiple areas (work, family, education, etc...). This can contribute to reduce the quality of patients life. From a gender perspective, in the literature there seems to be evidence that the undesirable social effects of obesity affect women more than men. To minimize the obesity impact people adopt proactive methods to lose weight. However the solution to this problem is not on medication but changes in lifestyle and in the proposal of inclusive aesthetic models. Also it is necessary to clear that the complex etiology of obesity can help to reduce the weight stigma and the negative consequences of this condition.

  3. What Causes Overweight and Obesity?

    MedlinePlus

    ... the endocrine system can cause overweight and obesity. Hypothyroidism . People with this condition have low levels of ... even when food intake is reduced. People with hypothyroidism also produce less body heat, have a lower ...

  4. The Gut Microbiome and Obesity.

    PubMed

    John, George Kunnackal; Mullin, Gerard E

    2016-07-01

    The gut microbiome consists of trillions of bacteria which play an important role in human metabolism. Animal and human studies have implicated distortion of the normal microbial balance in obesity and metabolic syndrome. Bacteria causing weight gain are thought to induce the expression of genes related to lipid and carbohydrate metabolism thereby leading to greater energy harvest from the diet. There is a large body of evidence demonstrating that alteration in the proportion of Bacteroidetes and Firmicutes leads to the development of obesity, but this has been recently challenged. It is likely that the influence of gut microbiome on obesity is much more complex than simply an imbalance in the proportion of these phyla of bacteria. Modulation of the gut microbiome through diet, pre- and probiotics, antibiotics, surgery, and fecal transplantation has the potential to majorly impact the obesity epidemic.

  5. Pharmacotherapies for Overeating and Obesity

    PubMed Central

    Yarnell, S; Oscar-Berman, M; Avena, NM; Blum, K; Gold, MS

    2013-01-01

    Obesity has become pandemic, and the annual cost in related illnesses and loss of productivity is already over $100 billion and rising. Research has shown that obesity can and does cause changes in behavior and in the brain itself that are very similar to changes caused by drugs of abuse. While food addiction is not the causal agent of all obesity, it is clear that many people no longer eat to survive, but instead survive to eat. This review considers the importance of the brain’s reward system in food intake. The review also examines research developments and current treatments for obesity, including diet and exercise, psychotherapy, surgical interventions, and pharmacotherapies. Finally we discuss alterations in American society that are necessary for change to occur, and the diffculties therein. PMID:23826512

  6. Obesity and hormonal contraceptive efficacy.

    PubMed

    Robinson, Jennifer A; Burke, Anne E

    2013-09-01

    Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

  7. Recurrent pregnancy loss and obesity.

    PubMed

    Sugiura-Ogasawara, Mayumi

    2015-05-01

    Recurrent pregnancy loss (RPL) was defined as two or more miscarriages. Antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities, particularly translocation and abnormal embryonic karyotype, are identifiable causes of RPL. Obesity may increase the risk of sporadic miscarriage in pregnancies conceived spontaneously. Obesity with body mass index (BMI)>30 kg/m2 is an independent risk factor for further miscarriage with odds ratio 1.7-3.5 in patients with early RPL. Obesity is associated with euploid miscarriage. Unexplained RPL with euploid embryo might be a common disease caused by both polymorphisms of multiple susceptibility genes and lifestyle factors such as women's age, obesity, and smoking. Patients with a history of RPL were found to have a higher risk of cardiovascular disease, celiac disease, gastric ulcer, gastritis, and atopic dermatitis. No study has examined the effect of weight loss on the prevention of further miscarriage in patients with RPL.

  8. Pharmacogenetics of obesity drug therapy.

    PubMed

    Guzman, A K; Ding, M; Xie, Y; Martin, K A

    2014-01-01

    As the prevalence and severity of obesity and its complications have risen significantly in worldwide populations, behavioral interventions alone have been inconsistent in promoting sufficient, sustained weight loss. Consequently, there has been intense interest in the development of anti-obesity medications as treatment strategies. When coupled with structured lifestyle modifications, pharmacotherapy can enhance weight loss. While less efficacious than bariatric surgery, drug therapy may be an alternative to surgery for some obese patients, and is an emerging strategy for weight maintenance. The goal of pharmacogenetics is to help identify patients who will benefit most from drug therapies while minimizing the risk of adverse effects. In this review, we summarize the pharmacogenetic literature on obesity drugs of the past (sibutramine, rimonabant), present (orlistat, lorcaserin, phentermine, topiramate), and future (buprioprion/naltrexone).

  9. Obesity in the ageing man.

    PubMed

    Michalakis, K; Goulis, D G; Vazaiou, A; Mintziori, G; Polymeris, A; Abrahamian-Michalakis, A

    2013-10-01

    As the population is ageing globally, both ageing and obesity are recognized as major public health challenges. The aim of this narrative review is to present and discuss the current evidence on the changes in body composition, energy balance and endocrine environment that occur in the ageing man. Obesity in the ageing man is related to changes in both body weight and composition due to alterations in energy intake and total energy expenditure. In addition, somatopenia (decreased GH secretion), late-onset hypogonadism (LOH), changes in thyroid and adrenal function, as well as changes in appetite-related peptides (leptin, ghrelin) and, most importantly, insulin action are related to obesity, abnormal energy balance, redistribution of the adipose tissue and sarcopenia (decreased muscle mass). A better understanding of the complex relationship of ageing-related endocrine changes and obesity could lead to more effective interventions for elderly men.

  10. Overweight and Obesity (For Parents)

    MedlinePlus

    ... Portions Under Control Metabolic Syndrome Weight Loss Surgery (Bariatric Surgery) Encouraging a Healthy Body Image Healthy Drinks for ... BMI) About Overweight and Obesity Who Can Get Weight Loss Surgery? Contact Us Print Resources Send to a Friend ...

  11. Are Pediatricians Diagnosing Obese Children?

    PubMed Central

    Thomas, Katharine; Urrego, Fernando

    2017-01-01

    Background: Pediatric obesity is the most prevalent nutritional disorder in American children. The detrimental social, psychological, and physiological effects of obesity call for pediatricians to address this health concern. The literature demonstrates that clinicians are underreporting the diagnosis of obesity in the pediatric setting. The primary purpose of this study was to determine if pediatricians at one pediatrics clinic in the Ochsner Health System are documenting the presence of an overweight or obese body mass index (BMI) as a diagnosis in the medical record. A secondary purpose of this study was to determine the demographics of all pediatric patients in the Ochsner Health System to be used for program development. Methods: A retrospective medical record review was conducted. Records from April 1, 2012 to April 1, 2016, were reviewed for the presence of the diagnosis of BMI classified as obese or overweight. Results: We analyzed a total of 175,066 records in this study. Of these records, 1.32% documented a diagnosis of obesity, and 0.5% documented a BMI score indicating overweight. The percentages of patient visits that met the Centers for Disease Control and Prevention criteria to be classified as obese or overweight were 28.66% and 30.41%, respectively. The majority of our pediatric patients were male (51.76%), white (43.31%), and 5-12 years old (43.80%). Conclusion: This study demonstrates that pediatricians at Ochsner Health Center for Children are not diagnosing patients who have unhealthy BMI scores as overweight or obese. Interventions are needed to increase the identification of children who may benefit from receiving resources that encourage a healthy lifestyle and optimal weight maintenance. PMID:28331453

  12. Obesity pharmacotherapy: What is next?

    PubMed Central

    Colon-Gonzalez, Francheska; Kim, Gilbert W.; Lin, Jieru E.; Valentino, Michael A.; Waldman, Scott A.

    2014-01-01

    The increase in obesity in the Unites States and around the world in the last decade is overwhelming. The number of overweight adults in the world surpassed 1 billion in 2008. Health hazards associated with obesity are serious and include heart disease, sleep apnea, diabetes, and cancer. Although lifestyle modifications are the most straightforward way to control weight, a large portion of the population may not be able to rely on this modality alone. Thus, the development of anti-obesity therapeutics represents a major unmet medical need. Historically, anti-obesity pharmacotherapies have been unsafe and minimally efficacious. A better understanding of the biology of appetite and metabolism provides an opportunity to develop drugs that may offer safer and more effective alternatives for weight management. This review discusses drugs that are currently on the market and in development as anti-obesity therapeutics based on their target and mechanism of action. It should serve as a roadmap to establish expectations for the near future for anti-obesity drug development. PMID:23103610

  13. Determinants and Consequences of Obesity

    PubMed Central

    Hruby, Adela; Manson, JoAnn E.; Qi, Lu; Malik, Vasanti S.; Rimm, Eric B.; Sun, Qi; Willett, Walter C.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Studies (NHS and NHS II) in addressing hypotheses regarding risk factors for and consequences of obesity. Methods. Narrative review of the publications of the NHS and NHS II between 1976 and 2016. Results. Long-term NHS research has shown that weight gain and being overweight or obese are important risk factors for type 2 diabetes, cardiovascular diseases, certain types of cancers, and premature death. The cohorts have elucidated the role of dietary and lifestyle factors in obesity, especially sugar-sweetened beverages, poor diet quality, physical inactivity, prolonged screen time, short sleep duration or shift work, and built environment characteristics. Genome-wide association and gene–lifestyle interaction studies have shown that genetic factors predispose individuals to obesity but that such susceptibility can be attenuated by healthy lifestyle choices. This research has contributed to evolving clinical and public health guidelines on the importance of limiting weight gain through healthy dietary and lifestyle behaviors. Conclusions. The NHS cohorts have contributed to our understanding of the risk factors for and consequences of obesity and made a lasting impact on clinical and public health guidelines on obesity prevention. PMID:27459460

  14. [Obesity - principles of surgical therapy].

    PubMed

    Weiner, R A

    2008-09-01

    The prevalence of obesity and the number of surgeries for morbid obesity are increasing worldwide. Conservative therapy is largely ineffective in producing maintenance of weight loss in morbidly obese patients, and surgery is therefore increasingly considered as the only available option for these patients. Until approximately 15 years ago, many patients and physicians regarded bariatric surgery as dangerous because it required a large laparotomy and was associated with a relatively high risk of complications. Since laparoscopic techniques have become available, however, the number of patients referred for surgery has been increasing steadily. The principles of standard procedures are independent of access, whether open or laparoscopic. The pathophysiologic mechanisms are restriction, malabsorption, or a combination of both. New findings in the field of endocrine and humoral regulations have shown that surgical procedures can induce complex changes in the regulation of enterohormones. These mechanisms are the basis for metabolic effects, especially in cases of diabetes mellitus type 2. Obesity surgery is known to be the most effective and longest-lasting treatment for morbid obesity and many related conditions, but mounting evidence now suggests that it may also be among the most effective treatments for metabolic diseases and conditions such as type 2 diabetes, hypertension, high cholesterol, nonalcoholic fatty liver disease, and obstructive sleep apnea. Surgery for severe obesity goes far beyond weight loss; benefits include improved quality of life and extended life expectancy.

  15. Does Metabolically Healthy Obesity Exist?

    PubMed Central

    Muñoz-Garach, Araceli; Cornejo-Pareja, Isabel; Tinahones, Francisco J.

    2016-01-01

    The relationship between obesity and other metabolic diseases have been deeply studied. However, there are clinical inconsistencies, exceptions to the paradigm of “more fat means more metabolic disease”, and the subjects in this condition are referred to as metabolically healthy obese (MHO).They have long-standing obesity and morbid obesity but can be considered healthy despite their high degree of obesity. We describe the variable definitions of MHO, the underlying mechanisms that can explain the existence of this phenotype caused by greater adipose tissue inflammation or the different capacity for adipose tissue expansion and functionality apart from other unknown mechanisms. We analyze whether these subjects improve after an intervention (traditional lifestyle recommendations or bariatric surgery) or if they stay healthy as the years pass. MHO is common among the obese population and constitutes a unique subset of characteristics that reduce metabolic and cardiovascular risk factors despite the presence of excessive fat mass. The protective factors that grant a healthier profile to individuals with MHO are being elucidated. PMID:27258304

  16. Obesity and kidney disease: Beyond the hyperfiltration.

    PubMed

    Mascali, A; Franzese, O; Nisticò, S; Campia, U; Lauro, D; Cardillo, C; Di Daniele, N; Tesauro, M

    2016-09-01

    In industrialized countries, overweight and obesity account for approximately 13.8% and 24.9% of the kidney disease observed in men and women, respectively. Moreover, obesity-associated glomerulopathy is now considered as "an emerging epidemic." Kidney function can be negatively impacted by obesity through several mechanisms, either direct or indirect. While it is well established that obesity represents the leading risk factor for type 2 diabetes and hypertension, awareness that obesity is associated with direct kidney damage independently of hypertension and diabetes is still not widespread. In this paper we will discuss the emerging role of adipose tissue, particularly in the visceral depot, in obesity-induced chronic kidney damage.

  17. [Obesity and diabetes mellitus].

    PubMed

    Tron'ko, N D; Zak, K P

    2013-12-01

    New literature data and the results of own researches concerning the role of excessive body weight and the development of type 2 diabetes mellitus in humans are presented in the analytical review. Inaccordance with current insights, obesity and type 2 diabetes are considered diseases of inflammatory nature, characterized by systemic chronic low-grade inflammation, where different kinds of cytokines are cardinally involved. Unfavourable life style, i.e. excessive, high-energy, and irrational nutrition--an excessive consumption of animal fats and foods containing the high amount of glucose and starch with an insufficient use of high fiber vegetables, fish and vitamin D, and also sedentary, inactive life style leads to adipocyte hypertrophy and migration of M1 macrophages into the adipose tissue (AT). As a result, there is a low-grade inflammation accompanied by an increased production of proinflammatory cytokines (IL-1, IL-6, TNF-α, etc.), adipokines (leptin, resistin, visfatin etc.) and chemokines (CCL2, CCL5, CCL26 and CX3C). Under the influence of these cytokines, on the one hand, IR "is emerged", and on the other--there is apoptosis of the β-cells, that should be followed by the occurrence of clinically diagnosed type 2 diabetes. However, there is also the opposite system in humans, protecting the organism from the development of type 2 diabetes, and including an increase in the formation of M2 macrophages and the increased formation of secretion of antidiabetic cytokines (IL-4, IL-10, IL-13, etc.) and adiponectin.

  18. 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.

  19. Antimicrobial Dose in Obese Patient

    PubMed Central

    Kassab, Sawsan; Syed Sulaiman, Syed Azhar; Abdul Aziz, Noorizan

    2007-01-01

    Introduction Obesity is a chronic disease that has become one of major public health issue in Malaysia because of its association with other disease states including cardiovascular disease and diabetes. Despite continuous efforts to educate the public about the health risks associated with obesity, prevalence of the disease continues to increase. Dosing of many medications are based on weight, limited data are available on how antimicrobial agents should be dosed in obesity. The aim of this case presentation is to discuss dose of antibiotic in obese patient. Case report: Patient: GMN, Malay, Female, 45 year old, 150kg, transferred from medical ward to ICU with problems of fever, orthopnea, sepsis secondary to nosocomial pneumonia. She was admitted to hospital a week ago for SOB on exertion, cyanosis, mildly dyspneic, somasthenia, bilateral ankle swelling. There was no fever, cough, chest pain, clubbing, flapping tremor. Her grand father has pre-morbid history of obesity, HPT, DM and asthma. She was non alcoholic, smoker, and not on diet control. The diagnosis Pickwickian syndrome was made. Patient was treated with IV Dopamine 11mcg/kg/min, IV Morphine 4mg/h. IV GTN 15mcg/min, IV Ca gluconate 10g/24h for 3/7, IV Zantac 50mg tds, IV Augmentin 1.2g tds, IV Lasix 40mg od, IV Plasil 10mg tds, S.c heparin 5000IU bd. patient become stable and moved to medical ward to continue her treatment. Discussion: The altered physiologic function seen in obese patients is a concern in patients receiving antimicrobial agents because therapeutic outcomes depend on achieving a minimum inhibitory concentration (MIC). The therapeutic effect of any drug can be altered when any of the 4 pharmacokinetic processes (absorption, distribution, metabolism, or elimination) are altered. Decreased blood flow rates and increased renal clearance in obese patients can affect drug distribution and elimination. Changes in serum protein levels can change the metabolism and distribution of drugs that are

  20. The genetics of human obesity.

    PubMed

    Waalen, Jill

    2014-10-01

    The heritability of obesity has long been appreciated and the genetics of obesity has been the focus of intensive study for decades. Early studies elucidating genetic factors involved in rare monogenic and syndromic forms of extreme obesity focused attention on dysfunction of hypothalamic leptin-related pathways in the control of food intake as a major contributor. Subsequent genome-wide association studies of common genetic variants identified novel loci that are involved in more common forms of obesity across populations of diverse ethnicities and ages. The subsequent search for factors contributing to the heritability of obesity not explained by these 2 approaches ("missing heritability") has revealed additional rare variants, copy number variants, and epigenetic changes that contribute. Although clinical applications of these findings have been limited to date, the increasing understanding of the interplay of these genetic factors with environmental conditions, such as the increased availability of high calorie foods and decreased energy expenditure of sedentary lifestyles, promises to accelerate the translation of genetic findings into more successful preventive and therapeutic interventions.

  1. Low Back Pain and Obesity

    PubMed Central

    Ibrahimi-Kaçuri, Dafina; Murtezani, Ardiana; Rrecaj, Shkurta; Martinaj, Merita; Haxhiu, Bekim

    2015-01-01

    Introduction: Low back pain poses a significant problem in clinics and public health. It presents one of the main problems with adults, since 70-80% of adults experience it at least once in their lifetime. Causes of the low back pain are numerous and often unknown. Objectives: The aim of the study is to find the most prevalent age group, pain localisation, and the frequency of physical therapy sessions in obese and non-obese subjects with LBP. Materials and Methods: The study has been conducted by the Physical Rehabilitation Service of the Occupational Medicine Institute, during one year period. The total number of patients studied was 101 and all were Kosovo Energy Corporation (KEC) employees. The study was retrospective. Results: Looking at the body weight index, out of 101 patients, 69.3% are classified as non-obese and 30.7% as obese. Using T-Test we have found a difference of high statistical significance between the average number of the physical therapy sessions applied in relation to the examined groups (T-Test=2.78, P=0.0065, so, P<0.01). Conclusion: Obesity and age have no direct influence in back pain, but they could prolong healing. Professional occupation and binding position are factors that affect back pain. Physical workload can cause the manifestation of sciatica; whereas psycho-social factors can prolong the overall healing process. PMID:26005262

  2. Kidney transplantation in obese patients

    PubMed Central

    Tran, Minh-Ha; Foster, Clarence E; Kalantar-Zadeh, Kamyar; Ichii, Hirohito

    2016-01-01

    The World Health Organization estimated that in 2014, over 600 million people met criteria for obesity. In 2011, over 30% of individuals undergoing kidney transplant had a body mass index (BMI) 35 kg/m2 or greater. A number of recent studies have confirmed the relationship between overweight/obesity and important comorbidities in kidney transplant patients. As with non-transplant surgeries, the rate of wound and soft tissue complications are increased following transplant as is the incidence of delayed graft function. These two issues appear to contribute to longer length of stay compared to normal BMI. New onset diabetes after transplant and cardiac outcomes also appear to be increased in the obese population. The impact of obesity on patient survival after kidney transplantation remains controversial, but appears to mirror the impact of extremes of BMI in non-transplant populations. Early experience with (open and laparoscopic) Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy support excellent weight loss (in the range of 50%-60% excess weight lost at 1 year), but experts have recommended the need for further studies. Long term nutrient deficiencies remain a concern but in general, these procedures do not appear to adversely impact absorption of immunosuppressive medications. In this study, we review the literature to arrive at a better understanding of the risks related to renal transplantation among individuals with obesity. PMID:27011911

  3. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

    PubMed Central

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan; Badran, Samir; Arco, Rocío; Pavón, Francisco Javier; Serrano, Antonia; Rivera, Patricia; Decara, Juan; Cuesta, Antonio Luis; Rodríguez-de-Fonseca, Fernando

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15 days. The status and expression of IL-6-signalling mediators and targets were investigated in relation to the steatosis and lipid content in blood and in liver. IL-6 administration in DIO mice markedly raised circulating levels of lipids, glucose and leptin, elevated fat liver content and aggravated steatosis. Under IL-6 treatment there was hepatic Stat3 activation and increased gene expression of Socs3 and Tnf-alpha whereas the gene expression of endogenous IL-6, IL-6-receptor, Stat3, Cpt1 and the enzymes involved in lipogenesis was suppressed. These data further implicate IL-6 in fatty liver disease modulation in the context of DIO, and indicate that continuous stimulation with IL-6 attenuates the IL-6-receptor response, which is associated with high serum levels of leptin, glucose and lipids, the lowering levels of lipogenic and Cpt1 hepatic enzymes and with increased Tnf-alpha hepatic expression, a scenario evoking that observed in IL-6-/- mice exposed to DIO and in obese Zucker rats. PMID:27333268

  4. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice.

    PubMed

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan; Badran, Samir; Arco, Rocío; Pavón, Francisco Javier; Serrano, Antonia; Rivera, Patricia; Decara, Juan; Cuesta, Antonio Luis; Rodríguez-de-Fonseca, Fernando; Baixeras, Elena

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15 days. The status and expression of IL-6-signalling mediators and targets were investigated in relation to the steatosis and lipid content in blood and in liver. IL-6 administration in DIO mice markedly raised circulating levels of lipids, glucose and leptin, elevated fat liver content and aggravated steatosis. Under IL-6 treatment there was hepatic Stat3 activation and increased gene expression of Socs3 and Tnf-alpha whereas the gene expression of endogenous IL-6, IL-6-receptor, Stat3, Cpt1 and the enzymes involved in lipogenesis was suppressed. These data further implicate IL-6 in fatty liver disease modulation in the context of DIO, and indicate that continuous stimulation with IL-6 attenuates the IL-6-receptor response, which is associated with high serum levels of leptin, glucose and lipids, the lowering levels of lipogenic and Cpt1 hepatic enzymes and with increased Tnf-alpha hepatic expression, a scenario evoking that observed in IL-6-/- mice exposed to DIO and in obese Zucker rats.

  5. There's Something about Obesity: Culture, Contagion, Rationality, and Children's Responses to Drinks "Created" by Obese Children

    ERIC Educational Resources Information Center

    Klaczynski, Paul A.

    2008-01-01

    Theories of the development of obesity stereotypes cannot easily explain the stigma associated with being obese. Evidence that important similarities exist between the symptoms of obesity and contagious illnesses, young children have "theories" of illnesses, and obesity stereotypes are among the earliest that children develop led to the hypothesis…

  6. Defining overweight and obesity in children

    MedlinePlus

    ... body fat. It is not the same as overweight, which means weighing too much. Obesity is becoming ... different age. To determine if a child is overweight or obese, experts compare BMI levels of children ...

  7. Behavioral management of the obese patient

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite countless diets, exercise regimens, drugs, and behavior modification strategies, the prevalence of obesity continues its relentless increase in both developed and developing nations. Although many necessary components to treat obesity have been identified, behavior modification remains the b...

  8. Recent advancements in drug treatment of obesity.

    PubMed

    Carter, Rebeca; Mouralidarane, Angelina; Ray, Shuvra; Soeda, Junpei; Oben, Jude

    2012-10-01

    The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.

  9. CDC Vital Signs: Progress on Childhood Obesity

    MedlinePlus

    ... 41MB] Read the MMWR Science Clips Progress on Childhood Obesity Many States Show Declines Language: English Español ( ... are more likely to be obese later in childhood and adolescence. In these older children and adolescents, ...

  10. Obesity in childhood and adolescence, genetic factors.

    PubMed

    Memedi, Rexhep; Tasic, Velibor; Nikolic, Erieta; Jancevska, Aleksandra; Gucev, Zoran

    2013-01-01

    Obesity and overweight are a pandemic phenomenon in the modern world. Childhood and adolescent obesity often ends up in obesity in adults. The costs of obesity and its consequences are staggering for any society, crippling for countries in development. The etiology is complex, but most often idiopathic. Hormonal, syndromic and medication-induced obesity are well investigated. Genetic causes are increasingly described. Novel technologies such as whole exome sequencing identify ever more candidate genes influencing or causing obesity. All insights into the complex problem of obesity in a team approach to treatment: diet, psychology, medications and surgery. We briefly review epidemiology, etiology, consequences and treatment approaches in childhood and adolescent obesity, with special emphasis on emerging knowledge of its genetics.

  11. Obesity May Not Compromise Knee Surgery Success

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164282.html Obesity May Not Compromise Knee Surgery Success Results similar ... over 35, so it's unclear if more severe obesity might increase the risk of meniscal repair failure, ...

  12. How Are Obesity and Overweight Diagnosed?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How are obesity & overweight diagnosed? Skip sharing on social media links ... and Blood Institute. (2012). How are overweight and obesity diagnosed? Retrieved August 8, 2012, from http://www. ...

  13. Genetic aspects of human obesity.

    PubMed

    Larder, Rachel; Lim, Chung Thong; Coll, Anthony P

    2014-01-01

    Obesity and its related metabolic consequences represent a major public health problem. Huge changes within the environment have undoubtedly contributed to the increased prevalence of obesity but genetic factors are also critical in determining an individual's predisposition to gain weight. The last two decades have seen a huge increase in the understanding of the mechanisms controlling appetitive behavior, body composition, and energy expenditure. Many regions throughout the central nervous system play critical roles in these processes but the hypothalamus, in particular, receives and orchestrates a variety of signals to bring about coordinated changes in energy balance. Reviewing data from human genetic and model organism studies, we consider how disruptions of hypothalamic pathways evolved to maintain energy homeostasis and go on to cause obesity. We highlight ongoing technological developments which continue to lead to novel insights and discuss how this increased knowledge may lead to effective therapeutic interventions in the future.

  14. Obesity. Part I--Pathogenesis.

    PubMed Central

    Bray, G A; Gray, D S

    1988-01-01

    Obesity--defined by a body mass index above 30 kg per m2--is a major problem for affluent nations. Its prevalence is higher in North America than in Europe--between 9% and 12% of the population. Reduced energy expenditure from exercise or metabolism or both may be an important contributory factor in the development of obesity because of a failure to reduce food intake sufficiently to maintain energy balance. A high ratio of abdominal circumference relative to gluteal circumference carries a twofold or greater risk of heart attack, stroke, hypertension, diabetes mellitus, gallbladder disease, and death. The effect of increased quantities of abdominal fat is greater than that of a similar increase in total body fat on the risks of ill health associated with obesity. Genetic factors appear to contribute about 25% to its etiology. Images PMID:3067447

  15. 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.

  16. [Association of obesity and depression].

    PubMed

    Rihmer, Zoltán; Purebl, György; Faludi, Gábor; Halmy, László

    2008-10-01

    It has been long known that the frequency of overweight and obese people is higher among depressed and bipolar patients than in the general population. The marked alteration of body weight (and appetite) is one of the most frequent of the 9 symptoms of major depressive episode, and these symptoms occur during recurrent episodes of depression with a remarkably high consequence. According to studies with representative adult population samples, in case of obesity (BMI over 30) unipolar or bipolar depression is significantly more frequently (20-45%) observable. Since in case of depressed patients appetite and body weight reduction is observable during the acute phase, the more frequent obesity in case of depressed patients is related (primarily) not only to depressive episodes, but rather to lifestyle factors, to diabetes mellitus also more frequently occurring in depressed patients, to comorbid bulimia, and probably to genetic-biological factors (as well as to pharmacotherapy in case of medicated patients). At the same time, according to certain studies, circadian symptoms of depression give rise to such metabolic processes in the body which eventually lead to obesity and insulin resistance. According to studies in unipolar and bipolar patients, 57-68% of patients is overweight or obese, and the rate of metabolic syndrome was found to be between 25-49% in bipolar patients. The rate of metabolic syndrome is further increased by pharmacotherapy. Low total and HDL cholesterol level increases the risk for depression and suicide and recent studies suggest that omega-3-fatty acids possess antidepressive efficacy. Certain lifestyle factors relevant to healthy metabolism (calorie reduction in food intake, regular exercise) may be protective factors related to depression as well. The depression- and possibly suicide-provoking effect of sibutramine and rimonabant used in the pharmacotherapy of obesity is one of the greatest recent challenges for professionals and patients

  17. Metabolically healthy obesity: origins and implications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    When humans eat more and exercise less, they tend to become obese and unhealthy. The molecular pathways that link obesity to serious diseases like Type 2 diabetes and cardiovascular disease have become a subject of intensive scientific investigation because the exploding prevalence of obesity worldw...

  18. Adenovirus 36 and Obesity: An Overview

    PubMed Central

    Ponterio, Eleonora; Gnessi, Lucio

    2015-01-01

    There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed. PMID:26184280

  19. Perspectives on Obesity: The Unknown Handicap.

    ERIC Educational Resources Information Center

    Wishon, Phillip M.; Childs, Ronald E.

    1984-01-01

    This review focuses on a classification of the concept of obesity, childhood growth patterns, current diagnostic procedures, physiological and psychological implications, etiology, environmental influences, and the special needs of the obese child. Obesity is viewed as a medical condition requiring medical and educational interventions. (Author/RH)

  20. Psychological Theory Seeks to Define Obesity.

    ERIC Educational Resources Information Center

    Burgard, Debby

    1993-01-01

    Examines various psychodynamic and behavioral theories in a discussion about obesity and mental health. It is revealed that modern theory finds no identifiable personality profile, behavior, or family structure influencing large weight gain thus discounting psychopathology as the cause of obesity. Individual assessments for causes of obesity are…

  1. Obesity and Poverty: A Growing Challenge

    ERIC Educational Resources Information Center

    Daniels, Dianne Yow; Queen, J. Allen; Schumacher, Donald

    2007-01-01

    This research study addresses the childhood obesity epidemic, which has seen the number of overweight children from the ages of 6 to 11 triple since the mid-1970s. The authors note that there are more than twice as many poor and obese adolescents compared with more affluent youths, and examine a number of factors linking obesity and poverty.…

  2. Might video games help remedy childhood obesity?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is the most prevalent health problem among children in the United States and globally, leading to diverse health problems and staggering costs. Most child obesity prevention interventions are not working well, or not at all. Part of the problem is that the causes of child obesity are not cle...

  3. Do School Lunches Contribute to Childhood Obesity?

    ERIC Educational Resources Information Center

    Schanzenbach, Diane Whitmore

    2009-01-01

    This paper assesses whether school lunches contribute to childhood obesity. I employ two methods to isolate the causal impact of school lunches on obesity. First, using panel data, I ?nd that children who consume school lunches are more likely to be obese than those who brown bag their lunches even though they enter kindergarten with the same…

  4. Paternalism, Obesity, and Tolerable Levels of Risk

    ERIC Educational Resources Information Center

    Merry, Michael S.

    2012-01-01

    Obesity describes an abnormally high fat accumulation that impairs health. It is crudely measured by a body mass index (BMI) of greater than 30 kg/sq meters. Obesity now ranks among the highest of concerns by the World Health Organization (WHO) and not only in countries of affluence; the figures of obesity worldwide have doubled since 1980 and the…

  5. The Consequences of Childhood Overweight and Obesity

    ERIC Educational Resources Information Center

    Daniels, Stephen R.

    2006-01-01

    Researchers are only gradually becoming aware of the gravity of the risk that overweight and obesity pose for children's health. In this article Stephen Daniels documents the heavy toll that the obesity epidemic is taking on the health of the nation's children. He discusses both the immediate risks associated with childhood obesity and the…

  6. Obesity, Metabolic Syndrome, and Physical Activity.

    ERIC Educational Resources Information Center

    Yeater, Rachel

    2000-01-01

    Discusses the scope of the problem of obesity in the United States, noting the health risks associated with being overweight or obese (e.g., gallstones, osteoarthritis, sleep apnea, and colon cancer); discussing the association of type-II diabetes mellitus with obesity; examining the effects of exercise on metabolic disease; and looking at…

  7. [The endocannabinoid system in obesity].

    PubMed

    Pataky, Zoltan; Bobbioni-Harsch, Elisabetta; Carpentier, Anne; Golay, Alain

    2013-03-27

    The endocannabinoid system is involved in the regulation of energy balance and metabolism. Endocannabinoids have central effects with raising appetite and hunger. On the other hand, different components of the endocannabinoid system are also found in peripheral organs and tissues and they could impact the lipid and glucose metabolism. Obesity is associated with an overactivity of the endocannabinoid system with increased both plasmatic and visceral adipose tissue levels. The amount of the intra-abdominal fat mass is an indicator of the peripheral endocannabinoid system dysregulation. Endocannabinoids-like molecules with more pronounced peripheral effects on lipids and glucose metabolism could be a new target of obesity treatment.

  8. Childhood obesity and the media.

    PubMed

    Hingle, Melanie; Kunkel, Dale

    2012-06-01

    This article assesses the role played by media in contributing to the current epidemic of childhood obesity. Electronic media use, often referred to as screen time, is significantly correlated with child adiposity. Although the causal mechanism that accounts for this relationship is unclear, it is well established that reducing screen time improves weight status. Media advertising for unhealthy foods contributes to obesity by influencing children's food preferences, requests, and diet. Industry efforts have failed to improve the nutritional quality of foods marketed on television to children, leading public health advocates to recommend government restrictions on child-targeted advertisements for unhealthy foods.

  9. Abdominal obesity and metabolic syndrome.

    PubMed

    Després, Jean-Pierre; Lemieux, Isabelle

    2006-12-14

    Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.

  10. Obesity and carotid artery remodeling

    PubMed Central

    Kozakova, M; Palombo, C; Morizzo, C; Højlund, K; Hatunic, M; Balkau, B; Nilsson, P M; Ferrannini, E

    2015-01-01

    Background/Objective: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions characterized by body size-dependent increase in stroke volume (SV) and blood pressure (BP). Subjects/Methods: Common carotid artery (CCA) luminal diameter (LD), IMT and CWS were measured in three different populations in order to study: (A) cross-sectional associations between SV, BP, anthropometric parameters and CCA LD (266 healthy subjects with wide range of body weight (24–159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects without CV complications and 88 non-obese subjects matched for gender and age). Results: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was significantly higher (28±3 μm) as compared with those in the lower quartiles (8±3, 16±4 and 16±3 μm, P=0.001, P<0.05 and P=0.01, respectively). In addition, CCA CWS decreased during the observational period in the highest LD quartile (from 54.2±8.6 to 51.6±7.4 kPa, P<0.0001). As compared with gender- and age-matched lean individuals, obese subjects had highly increased CCA LD and BP (P<0.0001 for both), but only slightly higher CWS (P=0.05) due to a significant increase in IMT (P=0.005 after adjustment for confounders). Conclusions: Our findings suggest that in obese subjects, the CCA wall thickens to compensate the luminal enlargement caused by body size-induced increase in SV, and therefore, to normalize the wall stress. CCA diameter in obesity could

  11. [Mechanisms of hypertension in obesity].

    PubMed

    López de Fez, C M; Gaztelu, M T; Rubio, T; Castaño, A

    2004-01-01

    Obesity is a chronic disease, considered to be an important risk factor in the development of coronary disease, hypertension, renal insufficiency and failure. Obesity contributes to hypertension by mechanisms such as: insulinic resistance and hyperinsulinaemia, increase of adrenergic activity and of concentrations of aldosterone, retention of sodium and water and increase of cardiac wear, alteration of the endothelial function, through molecules such as leptin and adiponectin and genetic factors. Many paths of research remain open. The angiotensin-converting-enzyme inhibitors (ACEI) and/or the angiotensin II receptor antagonists (ARA II) are first choice medicines because of their beneficial effect on insulinic resistance and sympathetic activity.

  12. Obesity and the lung: 3 · Obesity, respiration and intensive care

    PubMed Central

    Malhotra, A; Hillman, D

    2009-01-01

    Obesity is a major problem from a public health perspective and a difficult practical matter for intensivists. The obesity pandemic has required treating clinicians to develop an appreciation of the substantial pathophysiological effects of obesity on the various organ systems. The important physiological concepts are illustrated by focusing on obstructive sleep apnoea, obesity hypoventilation syndrome, abdominal compartment syndrome and ventilatory management of the obese patient with acute respiratory distress syndrome. PMID:18820119

  13. Postpartum Obesity: The Root Problem of Childhood Obesity?

    ERIC Educational Resources Information Center

    Keen, Valencia Browning; Potts, Claudia Sealey

    2011-01-01

    Remedying childhood obesity cannot take place without first identifying relevant issues commonly influencing gatekeepers of food for children as well as the role modeling for encouraging or discouraging daily activities. Children cannot drive to the store, form grocery lists or complete menu management tasks without adult assistance. Excessive…

  14. 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

  15. Muscle loss and obesity: the health implications of sarcopenia and sarcopenic obesity.

    PubMed

    Wannamethee, S Goya; Atkins, Janice L

    2015-11-01

    This paper reviews the health implications of obesity, sarcopenia and sarcopenic obesity on CVD and mortality in older adults and discusses the obesity paradox seen in patients with CVD. Obesity is a major public health problem with increasing prevalence worldwide. It is an established risk factor for cardiovascular morbidity and mortality in adult populations. However, there is controversy surrounding the effects of obesity as measured by BMI in older people, and overweight and obesity (BMI ⩾ 25 kg/m2) are apparently associated with increased survival in those with CVD (obesity paradox). Ageing is associated with an increase in visceral fat and a progressive loss of muscle mass which have opposing effects on mortality. Thus BMI is not a good indicator of obesity in older adults. Sarcopenia, the age-associated loss of skeletal muscle mass, is a major concern in ageing populations and has been associated with metabolic impairment, CVD risk factors, physical disability and mortality. Sarcopenia often coexists with obesity. Sarcopenic obesity is a new category of obesity in older adults who have high adiposity coupled with low muscle mass. To fully understand the effect of obesity on mortality in the elderly it is important to take muscle mass into account. The evidence suggests that sarcopenia with obesity may be associated with higher levels of metabolic disorders and an increased risk of mortality than obesity or sarcopenia alone. Efforts to promote healthy ageing should focus on both preventing obesity and maintaining or increasing muscle mass.

  16. Pediatric obesity: Causes, symptoms, prevention and treatment

    PubMed Central

    XU, SHUMEI; XUE, YING

    2016-01-01

    Pediatric or childhood obesity is the most prevalent nutritional disorder among children and adolescents worldwide. Approximately 43 million individuals are obese, 21–24% children and adolescents are overweight, and 16–18% of individuals have abdominal obesity. The prevalence of obesity is highest among specific ethnic groups. Obesity increases the risk of heart diseases in children and adults. Childhood obesity predisposes the individual to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and kidney diseases and causes reproductive dysfunction in adults. Obesity in children is a major health concern of the developed world. The National Health and Nutrition Examination Survey has reported that the prevalence of obesity is on the increase in all the pediatric age groups, in males and females, and in various ethnic and racial groups. Factors, such as eating habits, genetics, environment, metabolism, and lifestyle play an important role in the development of obesity. Over 90% of obesity cases are idiopathic and less than 10% are associated with genetic and hormonal causes. Obesity occurs when the body consumes more calories than it burns, through overeating and underexercising. The symptoms of obesity include breathing disorders, sleep apnea, chronic obstructive pulmonary disease, certain types of cancer such as prostate, bowel, breast and uterine, coronary heart disease, diabetes (type 2 in children), depression, liver and gallbladder problems, gastro-esophageal reflux disease, high blood pressure, high cholesterol, stroke, and joint diseases such as osteoarthritis, pain in knees and lower back. Environmental, behavioral such as consumption of convenience foods, genetic, and family factors contribute to pediatric obesity. Obesity can be countered through lower calorie consumption, weight loss and diet programs, as well as increased physical activity. A number of endogenous molecules including leptin, hypothalamic melanocortin 4 receptor

  17. Obesity, insulin resistance and breast cancer outcomes.

    PubMed

    Goodwin, Pamela J

    2015-11-01

    There is growing evidence that obesity is associated with poor outcomes in early stage breast cancer. This paper addresses four current areas of focus: 1. Is obesity associated with poor outcomes in all biologic subtypes of breast cancer? 2. Does obesity effect AI efficacy or estrogen suppression in the adjuvant setting? 3. What are the potential biologic underpinnings of the obesity-breast cancer association? 4. Are intervention studies warranted? If so, which interventions in which populations? Research is needed to resolve these questions; intervention trials involving lifestyle interventions or targeting the biology postulated to link obesity and cancer are recommended.

  18. From fat fruitfly to human obesity

    PubMed Central

    Smith, Wanli W.; Thomas, Joseph; Liu, Jingnan; Li, Tianxia; Moran, Timothy H.

    2014-01-01

    Obesity is a chronic metabolic disease that has become a global problem. Although a tremendous amount of effort has been spent to prevent and treat obesity, its etiology is still largely unknown and there are not yet sufficient strategies to control obesity. Recently, the fruit fly, Drosophila melanogaster, has become a useful model for studying metabolic homeostasis and obesity related disorders. The goal of this mini-review is to summarize the recent achievements of Drosophila models and to highlight the experimental protocols used in studying feeding behavior and energy homeostasis in the fly. The Drosophila models provide useful tools to understand obesity pathogenesis and to develop novel therapeutics. PMID:24508822

  19. Postpartum Care and Contraception in Obese Women.

    PubMed

    Maclean, Courtney C; Thompson, Ivana S

    2016-03-01

    Postpartum obese women have an increased risk of breastfeeding difficulties and depression. Retaining the pregnancy weight at 6 months postpartum predicts long-term obesity. Risks for weight retention include excessive gestational weight gain, ethnicity, socioeconomic status, diet, exercise, depression, and duration of breastfeeding. Exercise and reducing total caloric intake promote postpartum weight loss. Intrauterine devices and contraceptive implants are the most effective contraceptives for obese women. Contraceptive pills, patches, and vaginal rings are effective options; however, obese women should be made aware of a potential increased risk of venous thromboembolism. Vasectomy and hysteroscopic sterilization carry the least surgical risk for obese women.

  20. Childhood Obesity: Problems and Solutions

    ERIC Educational Resources Information Center

    Van Staveren, Tonia; Dale, Darren

    2004-01-01

    Schools and homes both play a role in contributing to the rising numbers of obese children. School teachers and administrators must do all they can to create a school environment that is conducive to children maintaining a healthy weight. Legislation designed to add quality physical education time to the school curriculum is imperative. Changes to…

  1. Childhood Obesity Demands New Approaches.

    ERIC Educational Resources Information Center

    Satter, Ellyn

    1991-01-01

    Health professionals suggest creating achievable goals in childhood obesity. The article recommends correcting factors that distort normal growth and providing positive eating and exercise management to slow weight gain. Rather than trying for weight loss, children must learn positive lifelong eating and exercise patterns and attitudes toward self…

  2. Rimonabant, Gastrointestinal Motility and Obesity

    PubMed Central

    Sun, Yan; Chen, Jiande

    2012-01-01

    Background: Obesity and overweight affect more than half of the US population and are associated with a number of diseases. Rimonabant, a cannabinoid receptor 1 blocker in the endocannabinoid (EC) system, was indicated in Europe for the treatment of obesity and overweight patients with associated risk factors but withdrawn on Jan, 2009 because of side effects. Many studies have reported the effects of rimonabant on gastrointestinal (GI) motility and food intake. The aims of this review are: to review the relationship of EC system with GI motility and food intake;to review the studies of rimonabant on GI motility, food intake and obesity;and to report the tolerance and side effects of rimonabant. Methods: the literature (Pubmed database) was searched using keywords: rimonabant, obesity and GI motility. Results: GI motility is related with appetite, food intake and nutrients absorption. The EC system inhibits GI motility, reduces emesis and increases food intake; Rimonabant accelerates gastric emptying and intestinal transition but decreases energy metabolism and food intake. There is rapid onset of tolerance to the prokinetic effect of rimonabant. The main side effects of rimonabant are depression and GI symptoms. Conclusions: Rimonabant has significant effects on energy metabolism and food intake, probably mediated via its effects on GI motility. PMID:23449551

  3. Burns in Morbidly Obese Patients,

    DTIC Science & Technology

    1992-12-01

    tract infection and one episode C obesity. The clinical records of these patients were reviewed in of sinusitis. Two patients had documented bacteremias...veloped pneumonia and two developed tracheobronchitis. 0 Research, seven of whom clearly fulfilled the criteria for morbid There were one urinary

  4. Markets and Childhood Obesity Policy

    ERIC Educational Resources Information Center

    Cawley, John

    2006-01-01

    In examining the childhood obesity epidemic from the perspective of economics, John Cawley looks at both possible causes and possible policy solutions that work through markets. The operation of markets, says Cawley, has contributed to the recent increase in childhood overweight in three main ways. First, the real price of food fell. In…

  5. Childhood Obesity: A Heavy Problem

    ERIC Educational Resources Information Center

    Costley, Kevin C.; Leggett, Timothy

    2010-01-01

    The youth of today are faced with a big problem; they are becoming more obese every day. The time of children playing outside all day and being extremely active has been overtaken by the television and video games. The days of sitting down as a family and eating a good healthy meal has been replaced by the rush to the nearest fast food…

  6. Understanding Adult Overweight and Obesity

    MedlinePlus

    ... Your provider can help you assess your risk. Culture A person's culture may also affect weight: Some cultures have foods with a lot of fat or ... less attractive. Also, because some people in our culture may view a person with obesity as lacking ...

  7. Fighting Student Obesity in School

    ERIC Educational Resources Information Center

    Hardy, Lawrence

    2006-01-01

    The biggest risk to children's health is one which happens incrementally as students move through the school grades and into adulthood. Obesity has reached such proportions that today's children could end up living two to five years less than they might otherwise, according to a 2005 study in the New England Journal of Medicine. According to the…

  8. Economic causes and consequences of obesity.

    PubMed

    Finkelstein, Eric A; Ruhm, Christopher J; Kosa, Katherine M

    2005-01-01

    Obesity is not only a health but also an economic phenomenon. This chapter (a) examines underlying economic causes, such as technological advancements, behind the obesity epidemic; (b) describes economic consequences of obesity, including increasing obesity-related medical expenditures; and (c) discusses the role of government in combating the obesity epidemic. Because of the high costs of obesity, and the fact that the majority of these costs are financed by taxpayers, there is a clear motivation for government to try to reduce these costs. However, because obesity may result from poor information and addictive behavior and/or as a result of living in an increasingly obesogenic environment, interventions will need to be multifaceted to ensure the best chance of success.

  9. Obesity, Nutrition and Liver Disease in Children

    PubMed Central

    Feldstein, Ariel E.; Patton-Ku, Dana; Boutelle, Kerri N.

    2013-01-01

    Synopsis The prevalence of childhood obesity has reached epidemic proportions in the US and many other parts of the world. With obesity comes a variety of adverse health outcomes and metabolic complications. The liver in particular seems to be significantly impacted by fat deposition in the presence of obesity. In this article we discuss several aspects of childhood obesity from epidemiology and associated metabolic complications, to management strategies and therapy with particular attention to the impact of obesity on the liver resulting in non-alcoholic or metabolic fatty liver disease. The deleterious effects of obesity on the liver and health overall can be significantly impacted by a culture that fosters sustained nutritional improvement and regular physical activity. Here we summarize the current evidence supporting pharmacologic, behavioral and dietary interventions for the management of obesity and fatty liver disease in children. PMID:24274876

  10. Predictors of obesity in Michigan Operating Engineers.

    PubMed

    Duffy, Sonia A; Cohen, Kathleen A; Choi, Seung Hee; McCullagh, Marjorie C; Noonan, Devon

    2012-06-01

    Blue collar workers are at risk for obesity. Little is known about obesity in Operating Engineers, a group of blue collar workers, who operate heavy earth-moving equipment in road building and construction. Therefore, 498 Operating Engineers in Michigan were recruited to participate in a cross-sectional survey to determine variables related to obesity in this group. Bivariate and multivariate analyses were conducted to determine personal, psychological, and behavioral factors predicting obesity. Approximately 45% of the Operating Engineers screened positive for obesity, and another 40% were overweight. Multivariate analysis revealed that younger age, male sex, higher numbers of self-reported co-morbidities, not smoking, and low physical activity levels were significantly associated with obesity among Operating Engineers. Operating Engineers are significantly at risk for obesity, and workplace interventions are needed to address this problem.

  11. Fetal and perinatal consequences of maternal obesity.

    PubMed

    Vasudevan, Chakrapani; Renfrew, Mary; McGuire, William

    2011-09-01

    In many industrialised countries, one in five women booking for antenatal care is obese. As well as affecting maternal health, maternal obesity may have important adverse consequences for fetal, neonatal and long-term health and well-being. Maternal obesity is associated with a higher risk of stillbirth, elective preterm birth and perinatal mortality. The incidence of severe birth defects, particularly neural tube and structural cardiac defects, appears to be higher in infants of obese mothers. Fetal macrosomia associated with maternal obesity and gestational diabetes predisposes infants to birth injuries, perinatal asphyxia and transitional problems such as neonatal respiratory distress and metabolic instability. Maternal obesity may also result in long-term health problems for offspring secondary to perinatal problems and to intrauterine and postnatal programming effects. Currently, the available interventions to prevent and treat maternal obesity are of limited proven utility and further research is needed to define the effects of maternal weight management interventions on fetal and neonatal outcomes.

  12. The worldwide epidemic of female obesity.

    PubMed

    Mitchell, Sheona; Shaw, Dorothy

    2015-04-01

    The rapidly rising number of individuals who are overweight and obese has been called a worldwide epidemic of obesity with >35% of adults today considered to be overweight or obese. Women are more likely to be overweight and obese than their male counterparts, which has far-reaching effects on reproductive health and specifically pregnancy, with obese women facing an increased risk of gestational diabetes, preeclampsia, operative delivery, fetal macrosomia, and neonatal morbidity. The etiology of obesity is highly complex encompassing genetic, environmental, physiologic, cultural, political, and socioeconomic factors, making it challenging to develop effective interventions on both a local and global scale. This article describes the extent and the cost of the obesity epidemic, which, although historically seen as a disease of high-income countries, is now clearly a global epidemic that impacts low- and middle-income countries and indigenous groups who bear an ever-increasing burden of this disease.

  13. Obesity and related consequences to ageing.

    PubMed

    Jura, Magdalena; Kozak, Leslie P

    2016-02-01

    Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

  14. Obesity-related asthma in adults.

    PubMed

    Bhatt, Nikunj A; Lazarus, Angeline

    2016-08-01

    Obesity as a risk factor for asthma has been identified in previous studies. Additionally, a disproportionate number of patients with severe or difficult-to-control asthma are obese. Patients with obesity-related asthma tend to have worse asthma control and quality of life disproportionate to their pulmonary function tests, are less responsive to corticosteroid therapy, and are more likely to have obesity-related comorbidities such as obstructive sleep apnea and gastroesophageal disease that complicate asthma treatment. With the increasing prevalence of obesity, the prevalence of asthma is anticipated to grow proportionally. Addressing weight loss and encouraging activity is essential in the management of obesity-related asthma. This article briefly overviews the epidemiology, unique distinguishing features, potential mechanisms, and approach to management of patients with obesity-related asthma in adults.

  15. Preventing Obesity and Eating Disorders in Adolescents.

    PubMed

    Golden, Neville H; Schneider, Marcie; Wood, Christine

    2016-09-01

    Obesity and eating disorders (EDs) are both prevalent in adolescents. There are concerns that obesity prevention efforts may lead to the development of an ED. Most adolescents who develop an ED did not have obesity previously, but some teenagers, in an attempt to lose weight, may develop an ED. This clinical report addresses the interaction between obesity prevention and EDs in teenagers, provides the pediatrician with evidence-informed tools to identify behaviors that predispose to both obesity and EDs, and provides guidance about obesity and ED prevention messages. The focus should be on a healthy lifestyle rather than on weight. Evidence suggests that obesity prevention and treatment, if conducted correctly, do not predispose to EDs.

  16. Can Raising Awareness about the Psychological Causes of Obesity Reduce Obesity Stigma?

    PubMed

    Khan, Sammyh S; Tarrant, Mark; Weston, Dale; Shah, Pooja; Farrow, Claire

    2017-02-19

    Obesity stigma largely remains a socially acceptable bias with harmful outcomes for its victims. While many accounts have been put forward to explain the bias, the role of obesity etiology beliefs has received little scrutiny. The research examined the effect that beliefs about the psychological etiology of obesity have on the expression of obesity stigma and the mechanisms underpinning this effect. Participants (N = 463) were asked to evaluate a target person with obesity after reading one of three possible etiologies: psychological, genetic, or behavioral. The presentation of a psychological etiology of obesity elicited less prejudice compared to behavioral causes but greater prejudice compared to genetic causes; observed differences were found to be a function of the agency ascribed to the target's obesity and empathy expressed for the target. The findings highlight the impact that communicating obesity in terms of psychological causes can have for the expression of obesity stigma.

  17. 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

  18. Obesity in the intensive care unit: risks and complications.

    PubMed

    Selim, Bernardo J; Ramar, Kannan; Surani, Salim

    2016-08-01

    The steady growing prevalence of critically ill obese patients is posing diagnostic and management challenges across medical and surgical intensive care units. The impact of obesity in the critically ill patients may vary by type of critical illness, obesity severity (obesity distribution) and obesity-associated co-morbidities. Based on pathophysiological changes associated with obesity, predominately in pulmonary reserve and cardiac function, critically ill obese patients may be at higher risk for acute cardiovascular, pulmonary and renal complications in comparison to non-obese patients. Obesity also represents a dilemma in the management of other critical care areas such as invasive mechanical ventilation, mechanical ventilation liberation, hemodynamic monitoring and pharmacokinetics dose adjustments. However, despite higher morbidity associated with obesity in the intensive care unit (ICU), a paradoxical lower ICU mortality ("obesity paradox") is demonstrated in comparison to non-obese ICU patients. This review article will focus on the unique pathophysiology, challenges in management, and outcomes associated with obesity in the ICU.

  19. The Critical Care Obesity Paradox and Implications for Nutrition Support.

    PubMed

    Patel, Jayshil J; Rosenthal, Martin D; Miller, Keith R; Codner, Panna; Kiraly, Laszlo; Martindale, Robert G

    2016-09-01

    Obesity is a leading cause of preventable death worldwide. The prevalence of obesity has been increasing and is associated with an increased risk for other co-morbidities. In the critical care setting, nearly one third of patients are obese. Obese critically ill patients pose significant physical and on-physical challenges to providers, including optimization of nutrition therapy. Intuitively, obese patients would have worse critical care-related outcome. On the contrary, emerging data suggests that critically ill obese patients have improved outcomes, and this phenomenon has been coined "the obesity paradox." The purposes of this review will be to outline the historical views and pathophysiology of obesity and epidemiology of obesity, describe the challenges associated with obesity in the intensive care unit setting, review critical care outcomes in the obese, define the obesity-critical care paradox, and identify the challenges and role of nutrition support in the critically ill obese patient.

  20. The hunger-obesity paradox: obesity in the homeless.

    PubMed

    Koh, Katherine A; Hoy, Jessica S; O'Connell, James J; Montgomery, Paul

    2012-12-01

    Despite stereotypes of the homeless population as underweight, the literature lacks a rigorous analysis of weight status in homeless adults. The purpose of this study is to present the body mass index (BMI) distribution in a large adult homeless population and to compare this distribution to the non-homeless population in the United States. Demographic, BMI, and socioeconomic variables from patients seen in 2007-2008 were collected from the Boston Health Care for the Homeless Program (BHCHP). This population was compared to non-homeless adults from the National Health and Nutrition Examination Survey (NHANES). Among 5,632 homeless adults, the mean BMI was 28.4 kg/m(2) and the prevalence of obesity was 32.3 %. Only 1.6 % of homeless adults were underweight. Compared to mean BMI in NHANES (28.6 kg/m(2)), the difference was not significant in unadjusted analysis (p = 0.14). Adjusted analyses predicting BMI or likelihood of obesity also showed that the homeless had a weight distribution not statistically different from the general population. Although underweight has been traditionally associated with homelessness, this study suggests that obesity may be the new malnutrition of the homeless in the United States.