scholarly journals Roles of Fatty Acid Oversupply and Impaired Oxidation in Lipid Accumulation in Tissues of Obese Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Nicholas D. Oakes ◽  
Ann Kjellstedt ◽  
Pia Thalén ◽  
Bengt Ljung ◽  
Nigel Turner
Keyword(s):  
Fatty Acid ◽  
Lipid Accumulation ◽  
Ex Vivo ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Zucker Rats ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
And Storage

To test the roles of lipid oversupply versus oxidation in causing tissue lipid accumulation associated with insulin resistance/obesity, we studiedin vivofatty acid (FA) metabolism in obese (Obese) and lean (Lean) Zucker rats. Indices of local FA utilization and storage were calculated using the partially metabolizable [9,10-3H]-(R)-2-bromopalmitate (3H-R-BrP) and [U-14C]-palmitate (14C-P) FA tracers, respectively. Whole-body FA appearance (Ra) was estimated from plasma14C-P kinetics. Whole-body FA oxidation rate (Rox) was assessed using3H2O production from3H-palmitate infusion, and tissue FA oxidative capacity was evaluatedex vivo. In the basal fasting state Obese had markedly elevated FA levels andRa, associated with elevated FA utilization and storage in most tissues. Estimated rates of muscle FA oxidation were not lower in obese rats and were similarly enhanced by contraction in both lean and obese groups. At comparable levels of FA availability, achieved by nicotinic acid,Roxwas lower in Obese than Lean. In Obese rats, FA oxidative capacity was 35% higher than that in Lean in skeletal muscle, 67% lower in brown fat and comparable in other organs. In conclusion, lipid accumulation in non-adipose tissues of obese Zucker rats appears to result largely from systemic FA oversupply.

Fatty acid synthesis in vivo and hepatic contribution to whole-body lipogenic rates in obese zucker rats

Lipids ◽  
1980 ◽  
Vol 15 (12) ◽  
pp. 993-998 ◽  
Author(s):  
R. Kannan ◽  
D. B. Learn ◽  
N. Baker ◽  
J. Elovson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Whole Body ◽  
Zucker Rats ◽  
Obese Zucker Rats

Effects of a unique conjugate of α-lipoic acid and γ-linolenic acid on insulin action in obese Zucker rats

2000 ◽  
Vol 278 (2) ◽  
pp. R453-R459 ◽  
Author(s):  
J. Anthony Peth ◽  
Tyson R. Kinnick ◽  
Erik B. Youngblood ◽  
Hans J. Tritschler ◽  
Erik J. Henriksen
Keyword(s):  
Fatty Acid ◽  
Essential Fatty Acid ◽  
Glucose Transport ◽  
Lipoic Acid ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Additive Effects ◽  
Insulin Resistant ◽  
Obese Zucker Rats

The purpose of this study was to assess the individual and interactive effects of the antioxidant α-lipoic acid (LPA) and the n-6 essential fatty acid γ-linolenic acid (GLA) on insulin action in insulin-resistant obese Zucker rats. LPA, GLA, and a unique conjugate consisting of equimolar parts of LPA and GLA (LPA-GLA) were administered for 14 days at 10, 30, or 50 mg ⋅ kg body wt− 1 ⋅ day− 1. Whereas LPA was without effect at 10 mg/kg, at 30 and 50 mg/kg it elicited 23% reductions ( P < 0.05) in the glucose-insulin index (the product of glucose and insulin areas under the curve during an oral glucose tolerance test and an index of peripheral insulin action) that were associated with significant increases in insulin-mediated (2 mU/ml) glucose transport activity in isolated epitrochlearis (63–65%) and soleus (33–41%) muscles. GLA at 10 and 30 mg/kg caused 21–25% reductions in the glucose-insulin index and 23–35% improvements in insulin-mediated glucose transport in epitrochlearis muscle. The beneficial effects of GLA disappeared at 50 mg/kg. At 10 and 30 mg/kg, the LPA-GLA conjugate elicited 29 and 38% reductions in the glucose-insulin index. These LPA-GLA-induced improvements in whole body insulin action were accompanied by 28–63 and 38–57% increases in insulin-mediated glucose transport in epitrochlearis and soleus muscles and resulted from the additive effects of LPA and GLA. At 50 mg/kg, the metabolic improvements due to LPA-GLA were substantially reduced. In summary, these results indicate that the conjugate of the antioxidant LPA and the n-6 essential fatty acid GLA elicits significant dose-dependent improvements in whole body and skeletal muscle insulin action on glucose disposal in insulin-resistant obese Zucker rats. Moreover, these actions of LPA-GLA are due to the additive effects of its individual components.

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

1988 ◽  
Vol 254 (3) ◽  
pp. E342-E348 ◽  
Author(s):  
S. Krief ◽  
R. Bazin ◽  
F. Dupuy ◽  
M. Lavau
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Glucose Utilization ◽  
Whole Body ◽  
Glucose Disposal ◽  
Zucker Rats ◽  
Brown Adipose ◽  
Obese Rats ◽  
Proximal Intestine

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 [3-3H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia (140 vs. 55 microU/ml). In obese compared with lean rats, tissue glucose uptake (assessed by the 2-deoxyglucose technique) 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. Our 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.

Muscle bioenergetics in obese Zucker rats

1994 ◽  
Vol 266 (3) ◽  
pp. E410-E417 ◽  
Author(s):  
M. Klein ◽  
P. Kaminsky ◽  
P. M. Walker ◽  
J. Straczek ◽  
F. Barbe ◽  
...  
Keyword(s):  
Inorganic Phosphate ◽  
Zucker Rats ◽  
Resonance Spectroscopy ◽  
Muscle Stimulation ◽  
Energetic Metabolism ◽  
Subsequent Recovery ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Total Creatine

The purpose of this study was to investigate the energetic metabolism in obese Zucker rats, using phosphorus nuclear magnetic resonance spectroscopy at rest and during a 2-Hz muscle stimulation and subsequent recovery. Animals were anesthetized with ketamine (150 mg/kg ip). Fed obese rats and 2-day-fasted obese rats were compared with their normally fed and 2-day-fasted lean litter mates. No differences were found between the two groups for ATP, total creatine, phosphocreatine (PCr), and intracellular pH. Starvation in lean rats resulted in a significant fall in inorganic phosphate (Pi), increased resting ADP level, and decreased PCr and ADP recovery after stimulation. The obese rats exhibited a decreased PCr/Pi and increased ADP at rest and a decreased PCr resynthesis and ADP metabolization rate after stimulation. Muscle stimulation in fasted obese rats induced higher PCr depletion and more pronounced acidosis. These results suggest an in vivo mitochondrial metabolism dysfunction in fasted lean as well as in fed and fasted obese rats.

Obesity lowers hyperglycemic threshold for impaired in vivo endothelial nitric oxide function

2002 ◽  
Vol 283 (1) ◽  
pp. H391-H397 ◽  
Author(s):  
H. G. Bohlen ◽  
Geoffrey P. Nase
Keyword(s):  
Nitric Oxide ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Zucker Rats ◽  
Kinase C ◽  
Lower Glucose ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Endothelial Nitric Oxide

Obesity is a risk for type II diabetes mellitus and increased vascular resistance. Disturbances of nitric oxide (NO) physiology occur in both obese animals and humans. In obese Zucker rats, we determined whether a protein kinase C-βII (PKC-βII) mechanism may lower the resting NO concentration ([NO]) and predispose endothelial NO abnormalities at lower glucose concentrations than occur in lean rats. NO was measured with microelectrodes touching in vivo intestinal arterioles. At rest, the [NO] in obese Zucker rats was 60 nm less than normal or about a 15% decline. After local blockade of PKC-βII with LY-333531, the [NO] increased ∼90 nm in obese rats but did not change in lean rats. In lean rats, administration of 300 mg/dl d-glucose for 45 min depressed endothelium-dependent dilation; only 200 mg/dl was required in obese animals. These various observations indicate that resting [NO] is depressed in obese rats by a PKC-βII mechanism and the hyperglycemic threshold for endothelial NO suppression is reduced to 200 mg/dl d-glucose.

scholarly journals Heat shock proteins: in vivo heat treatments reveal adipose tissue depot-specific effects

2015 ◽  
Vol 118 (1) ◽  
pp. 98-106 ◽  
Author(s):  
Robert S. Rogers ◽  
Marie-Soleil Beaudoin ◽  
Joshua L. Wheatley ◽  
David C. Wright ◽  
Paige C. Geiger
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Ex Vivo ◽  
Heat Treatments ◽  
Whole Body ◽  
Sham Treatment ◽  
Shock Proteins

Heat treatments (HT) and the induction of heat shock proteins (HSPs) improve whole body and skeletal muscle insulin sensitivity while decreasing white adipose tissue (WAT) mass. However, HSPs in WAT have been understudied. The purpose of the present study was to examine patterns of HSP expression in WAT depots, and to examine the effects of a single in vivo HT on WAT metabolism. Male Wistar rats received HT (41°C, 20 min) or sham treatment (37°C), and 24 h later subcutaneous, epididymal, and retroperitoneal WAT depots (SCAT, eWAT, and rpWAT, respectively) were removed for ex vivo experiments and Western blotting. SCAT, eWAT, and rpWAT from a subset of rats were also cultured separately and received a single in vitro HT or sham treatment. HSP72 and HSP25 expression was greatest in more metabolically active WAT depots (i.e., eWAT and rpWAT) compared with the SCAT. Following HT, HSP72 increased in all depots with the greatest induction occurring in the SCAT. In addition, HSP25 increased in the rpWAT and eWAT, while HSP60 increased in the rpWAT only in vivo. Free fatty acid (FFA) release from WAT explants was increased following HT in the rpWAT only, and fatty acid reesterification was decreased in the rpWAT but increased in the SCAT following HT. HT increased insulin responsiveness in eWAT, but not in SCAT or rpWAT. Differences in HSP expression and induction patterns following HT further support the growing body of literature differentiating distinct WAT depots in health and disease.

scholarly journals Corticosterone-dependent metabolic and neuroendocrine abnormalities in obese Zucker rats in relation to feeding

2005 ◽  
Vol 288 (1) ◽  
pp. E254-E266 ◽  
Author(s):  
Martine Duclos ◽  
Elena Timofeeva ◽  
Chantal Michel ◽  
Denis Richard
Keyword(s):  
Food Deprivation ◽  
Hpa Axis ◽  
Stress Reaction ◽  
Whole Body ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Experimental Conditions ◽  
Metabolic Defects ◽  
Obese Rats ◽  
Obese Zucker Rats

The obese Zucker ( fa/fa) rat is characterized by hyperphagia, hyperinsulinemia, an increase in fat deposition, and a hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis in fa/fa rats is hypersensitive to stressful experimental conditions. Food deprivation even leads to a stress reaction in obese fa/fa rats. The present study was conducted to investigate the role of corticosterone in obese rats on the basal, fasting, and postprandial metabolic rate as well as on the central expression of the thyrotropin-releasing hormone (TRH) in these conditions. In addition, the study was aimed at clarifying whether the high levels of corticosterone in obese rats are responsible for the induction of the stress reaction to food deprivation in these animals. The present results demonstrate that whole body fat oxidation and postprandial metabolic responses in obese Zucker rats were improved by adrenalectomy (ADX). At the level of the central nervous system, ADX reversed a decrease in TRH mRNA expression in the paraventricular hypothalamus (PVH) detected in fasting animals. Considering all feeding conditions, the obese rats demonstrated lower TRH mRNA levels compared with lean animals. ADX resulted in an enhanced postprandial activation of the parvocellular PVH. In contrast, the magnocellular part of the PVH was less responsive to refeeding in ADX animals. Finally, ADX failed to prevent the stress response of obese rats to food deprivation. The present results provide evidence that the removal of adrenals resolve some of the metabolic defects encountered in obese Zucker rats. They also demonstrate that not all the abnormalities of the obese Zucker rats are attributable to the hyperactivity of the HPA axis.

scholarly journals Regulation of the renal thiazide-sensitive Na-Cl cotransporter, blood pressure, and natriuresis in obese Zucker rats treated with rosiglitazone

2005 ◽  
Vol 289 (2) ◽  
pp. F442-F450 ◽  
Author(s):  
Osman Khan ◽  
Shahla Riazi ◽  
Xinqun Hu ◽  
Jian Song ◽  
James B. Wade ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Control Diet ◽  
Zucker Rats ◽  
Receptor Subtype ◽  
Protein Abundance ◽  
Lean Control ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Nacl Load

Previously, we showed an increase in protein abundance of the renal thiazide-sensitive Na-Cl cotransporter (NCC) in young, prediabetic, obese Zucker rats relative to lean age mates (Bickel CA, Verbalis JF, Knepper MA, and Ecelbarger CA. Am J Physiol Renal Physiol 281: F639–F648, 2001). To test whether this increase correlated with increased thiazide sensitivity (NCC activity) and blood pressure, and could be modified by insulin-sensitizing agents, we treated lean and obese Zucker rats (9 wk old) with either a control diet or this diet supplemented with 3 mg/kg body wt rosiglitazone (RGZ), a peroxisomal proliferator-activated receptor subtype γ agonist and potent insulin-sensitizing agent, for 12 wk ( n = 9/group). The rise in blood pressure, measured continuously by radiotelemetry, was significantly blunted in the RGZ-treated obese rats. Similarly, blood glucose and urinary albumin were markedly decreased in these rats. RGZ-treated rats whether lean or obese excreted a NaCl load faster but excreted less sodium in response to hydrochlorothiazide, applied as a novel in vivo measure of NCC activity. Obese rats had increased renal protein abundance and urinary excretion of NCC; however, this was not significantly reduced by RGZ (densitometry in cortex homogenate − %lean control): 100 ± 9, 93 ± 4, 124 ± 9, and 141 ± 14 for lean control, lean RGZ, obese control, and obese RGZ, respectively. Subcellular localization, as evaluated by confocal microscopy and immunoblotting following differential centrifugation, of NCC was not different between rat groups. Overall, RGZ reduced blood pressure and thiazide sensitivity; however, the mechanism(s) did not seem to involve a decrease in NCC protein abundance or cellular location. Decreased NCC activity may have contributed to the maintenance of normotension in RGZ-treated obese rats.

Hepatic palmitate metabolism in fasting Zucker rats: effect of lactate on partitioning

1984 ◽  
Vol 246 (6) ◽  
pp. R1011-R1014
Author(s):  
M. J. Azain ◽  
R. J. Martin
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Hepatocytes ◽  
Zucker Rats ◽  
Energy Sources ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Acid Esterification ◽  
Palmitate Metabolism ◽  
Fatty Acid Esterification

Hepatocytes were isolated from 48-h fasted lean and obese Zucker rats and incubated with [1–14C] palmitate. The partitioning of fatty acids to oxidation and esterification products and the effect of lactate or glucose on this partitioning were studied. With palmitate as the only substrate, the cells from the lean rats oxidized 80% of the palmitate that was metabolized compared with only 35% oxidation in the cells from the obese rats. Thus fatty acid esterification remained the predominate pathway of palmitate metabolism in the hepatocytes from fasting obese rats. The addition of lactate to the cells from the lean rats decreased oxidation and increased esterification to levels similar to those in the obese rat hepatocytes. Glucose had similar effects on esterification in lean rat hepatocytes but was less potent than lactate. The cells from the obese rats were insensitive to the addition of lactate or glucose. These studies indicate that the inability of hepatocytes from obese rats to induce ketogenesis from exogenous fatty acids after a 48-h fast and their insensitivity to added lactate or glucose may be related to the availability of endogenous energy sources in the obese liver that can be oxidized and thus inhibit ketogenesis and support fatty acid esterification.

scholarly journals Study of some factors controlling fatty acid oxidation in liver mitochondria of obese Zucker rats

1986 ◽  
Vol 239 (1) ◽  
pp. 103-108 ◽  
Author(s):  
P Clouet ◽  
C Henninger ◽  
J Bézard
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Liver Mitochondria ◽  
Carnitine Palmitoyltransferase ◽  
Urate Oxidase ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Carnitine Palmitoyltransferase I

Livers of genetically obese Zucker rats showed, compared with lean controls, hypertrophy and enrichment in triacylglycerols, indicating that fatty acid metabolism was directed towards lipogenesis and esterification rather than towards fatty acid oxidation. Mitochondrial activities of cytochrome c oxidase and monoamine oxidase were significantly lower when expressed per g wet wt. of liver, whereas peroxisomal activities of urate oxidase and palmitoyl-CoA-dependent NAD+ reduction were unchanged. Liver mitochondria were able to oxidize oleic acid at the same rate in both obese and lean rats. For reactions occurring inside the mitochondria, e.g. octanoate oxidation and palmitoyl-CoA dehydrogenase, no difference was found between both phenotypes. Total carnitine palmitoyl-, octanoyl- and acetyl-transferase activities were slightly higher in mitochondria from obese rats, whereas the carnitine content of both liver tissue and mitochondria was significantly lower in obese rats compared with their lean littermates. The carnitine palmitoyltransferase I activity was slightly higher in liver mitochondria from obese rats, but this enzyme was more sensitive to malonyl-CoA inhibition in obese than in lean rats. The above results strongly suggest that the impaired fatty acid oxidation observed in the whole liver of obese rats is due to the diminished transport of fatty acids across the mitochondrial inner membrane via the carnitine palmitoyltransferase I. This effect could be reinforced by the decreased mitochondrial content per g wet wt. of liver. The depressed fatty acid oxidation may explain in part the lipid infiltration of liver observed in obese Zucker rats.

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