scholarly journals Oral supplementation of propionyl-l-carnitine reduces body weight and hyperinsulinaemia in obese Zucker rats

2009 ◽  
Vol 102 (8) ◽  
pp. 1145-1153 ◽  
Author(s):  
Carmen Mingorance ◽  
Maria Gonzalez del Pozo ◽  
Maria Dolores Herrera ◽  
Maria Alvarez de Sotomayor
Keyword(s):  
Insulin Resistance ◽  
Animal Model ◽  
Body Weight ◽  
Food Intake ◽  
Vascular Function ◽  
Mesenteric Arteries ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Oral Glucose ◽  
Obese Zucker Rats

Propionyl-l-carnitine (PLC) is an SCFA esterified to carnitine that plays an important role in fatty acid oxidation and energy expenditure, in addition to having a protective effect on the endothelium. In order to evaluate the effect of PLC on an animal model of obesity, insulin resistance and, consequently, endothelial dysfunction, lean and obese Zucker rats (OZR) received either vehicle- or PLC-supplemented drinking water (200 mg/kg per d) for 20 weeks. Body weight, food intake, systolic blood pressure and heart rate were controlled weekly and an oral glucose tolerance test was performed. Fasting glucose, TAG, cholesterol, HDL, NEFA, adiponectin and insulin were analysed in serum. Visceral adipose tissue and liver were weighed and liver TAG liver composition was evaluated. Endothelial and vascular functions were assessed in the aorta and small mesenteric arteries by response to acetylcholine, sodium nitroprusside and phenylephrine (Phe); NO participation was evaluated after incubation with the NO synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME) and endothelial NOS protein expression by Western blotting. PLC decreased body-weight gain, food intake, adiposity, insulin serum concentration and TAG liver content and improved insulin resistance. Aortae from OZR receiving either vehicle or PLC exhibited a lower contractile response to Phe. PLC-treated OZR showed an enhanced release of endothelial NO upon the adrenergic stimulation. The protection of vascular function found after treatment with PLC in an animal model of insulin resistance supports the necessity of clinical trials showing the effect of l-carnitine supplements on metabolic disorders.

Intraventricular insulin reduces food intake and body weight of lean but not obese zucker rats

Appetite ◽  
1986 ◽  
Vol 7 (4) ◽  
pp. 381-386 ◽  
Author(s):  
H. Ikeda ◽  
D.B. West ◽  
J.J. Pustek ◽  
D.P. Figlewicz ◽  
M.R.C. Greenwood ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Zucker Rats ◽  
Obese Zucker Rats

scholarly journals Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats

2005 ◽  
Vol 153 (6) ◽  
pp. 963-969 ◽  
Author(s):  
Dorte X Gram ◽  
Anker J Hansen ◽  
Michael Wilken ◽  
Torben Elm ◽  
Ove Svendsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Sensory Nerve ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Nerve Activity ◽  
Calcitonin Gene ◽  
Obese Rats ◽  
Obese Zucker Rats

Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity – and therefore might be involved in the pathophysiology – is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin. Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1±3.4 pmol/l in pre-obese Zucker rats vs 6.9±1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3±0.2 mmol/l vs 5.1±0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8±0.3 mmol/l vs 8.6±0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver. Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.

987 des-acyl Ghrelin Suppresses Food Intake and Body Weight Gain in Adult Obese Zucker Rats

2008 ◽  
Vol 134 (4) ◽  
pp. A-148 ◽  
Author(s):  
Andreas Stengel ◽  
Anna-Sophia Wisser ◽  
Peter Kobelt ◽  
Miriam Goebel ◽  
Bertram Wiedenmann ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Acyl Ghrelin

Memory impairment in obese Zucker rats: An investigation of cognitive function in an animal model of insulin resistance and obesity.

2005 ◽  
Vol 119 (5) ◽  
pp. 1389-1395 ◽  
Author(s):  
Gordon Winocur ◽  
Carol E. Greenwood ◽  
Gerardo G. Piroli ◽  
Claudia A. Grillo ◽  
Leah R. Reznikov ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Animal Model ◽  
Cognitive Function ◽  
Memory Impairment ◽  
Zucker Rats ◽  
Obese Zucker Rats

Central melanocortin system modulates energy intake and expenditure of obese and lean Zucker rats

2001 ◽  
Vol 281 (2) ◽  
pp. R444-R451 ◽  
Author(s):  
Joyce J. Hwa ◽  
Lorraine Ghibaudi ◽  
Jun Gao ◽  
Eric M. Parker
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Receptor Agonist ◽  
Melanocortin Receptor ◽  
Zucker Rats ◽  
Light Cycle ◽  
Weight Regulation ◽  
Central Administration ◽  
Body Weight Regulation ◽  
Obese Zucker Rats

Melanocortins play a critical role in appetite and body weight regulation, because manipulations of this pathway can lead to the development of obesity in several animal models. The purpose of this study was to use a melanocortin receptor agonist and antagonist to evaluate the involvement of melanocortins in feeding, energy metabolism, and body weight regulation in lean and obese Zucker rats. Central administration of a melanocortin receptor antagonist (SHU9119) elevated food intake and body weight of lean Zucker rats but had little effect in obese Zucker rats. In contrast, the melanocortin receptor agonist MTII reduced food intake in both lean and obese rats but was more potent in the obese Zucker rats. These data indicate the existence of functional melanocortin receptors in both lean and obese Zucker rats but suggest that obese Zucker rats have reduced endogenous melanocortin tone. In addition to its effects on food intake, MTII infusion elevated oxygen consumption and decreased respiratory quotient dose dependently during the light cycle. Our data suggest that a melanocortin receptor agonist can induce weight loss by increasing energy expenditure and promoting body fat utilization in addition to its inhibitory effects on food intake in both obese and lean Zucker rats.

Effects of clenbuterol on insulin resistance in conscious obese Zucker rats

2001 ◽  
Vol 280 (4) ◽  
pp. E554-E561 ◽  
Author(s):  
Shujia J. Pan ◽  
Joe Hancock ◽  
Zhenping Ding ◽  
Donovan Fogt ◽  
Mancheong Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Chronic Administration ◽  
Abdominal Fat ◽  
Zucker Rats ◽  
Control Group ◽  
Obese Zucker Rats ◽  
Long Acting

The present study was conducted to determine the effect of chronic administration of the long-acting β2-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats ( fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin · kg−1 · min−1) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.

scholarly journals Dehydroepiandrosterone Decreases Serum Tumor Necrosis Factor-α and Restores Insulin Sensitivity: Independent Effect from Secondary Weight Reduction in Genetically Obese Zucker Fatty Rats*

Endocrinology ◽  
1998 ◽  
Vol 139 (7) ◽  
pp. 3249-3253 ◽  
Author(s):  
Mari Kimura ◽  
Shun-ichi Tanaka ◽  
Yoshihiko Yamada ◽  
Yoshihiro Kiuchi ◽  
Tadashi Yamakawa ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Tumor Necrosis ◽  
Zucker Rats ◽  
Tnf Α ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Dhea Treatment ◽  
Necrosis Factor

Abstract 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)-α, 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-α independently, and that both may ameliorate insulin resistance in obese Zucker fatty rats.

Tesaglitazar, a dual PPARα/γ agonist, ameliorates glucose and lipid intolerance in obese Zucker rats

2005 ◽  
Vol 289 (4) ◽  
pp. R938-R946 ◽  
Author(s):  
Nicholas D. Oakes ◽  
Pia Thalén ◽  
Therese Hultstrand ◽  
Severina Jacinto ◽  
Germán Camejo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Glucose Tolerance ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Therapeutic Effects ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Mass Load ◽  
Obese Zucker Rats

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor α/γ agonist, tesaglitazar, 3 μmol·kg−1·day−1 for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

scholarly journals Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat

2010 ◽  
Vol 299 (3) ◽  
pp. G751-G760 ◽  
Author(s):  
Derek M. Culnan ◽  
Vance Albaugh ◽  
Mingjie Sun ◽  
Christopher J. Lynch ◽  
Charles H. Lang ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Zucker Rats ◽  
Ileal Interposition ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
Glucagon Like Peptide 1

The hindgut hypothesis posits improvements in Type 2 diabetes after gastric bypass surgery are due to enhanced delivery of undigested nutrients to the ileum, which increase incretin production and insulin sensitivity. The present study investigates the effect of ileal interposition (IT), surgically relocating a segment of distal ileum to the proximal jejunum, on glucose tolerance, insulin sensitivity, and glucose transport in the obese Zucker rat. Two groups of obese Zucker rats were studied: IT and sham surgery ad libitum fed (controls). Changes in food intake, body weight and composition, glucose tolerance, insulin sensitivity and tissue glucose uptake, and insulin signaling as well as plasma concentrations of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide were measured. The IT procedure did not significantly alter food intake, body weight, or composition. Obese Zucker rats demonstrated improved glucose tolerance 3 wk after IT compared with the control group ( P < 0.05). Euglycemic, hyperinsulinemic clamp and 1-[14C]-2-deoxyglucose tracer studies indicate that IT improves whole body glucose disposal, insulin-stimulated glucose uptake, and the ratio of phospho- to total Akt ( P < 0.01 vs. control) in striated muscle. After oral glucose, the plasma concentration of glucagon-like peptide-1 was increased, whereas GIP was decreased following IT. Enhanced nutrient delivery to the ileum after IT improves glucose tolerance, insulin sensitivity and muscle glucose uptake without altering food intake, body weight, or composition. These findings support the concept that anatomic and endocrine alterations in gut function play a role in the improvements in glucose homeostasis after the IT procedure.

Sign in / Sign up

Export Citation Format

Share Document