Training down-regulates fatty acid synthase and body fat in obese Zucker rats

ABSTRACT Background Specific dietary proteins exert strong health-related effects compared with casein. Objective Herein, the hypothesis was tested using screening and conventional biochemical and molecular biological techniques that protein-rich insect meal compared with casein influences metabolic health in hyperlipidemic rats. Methods A 4-wk feeding trial with male, 8-wk-old homozygous obese Zucker rats (n = 36) and male, 8-wk-old heterozygous lean Zucker rats (n = 12) was performed. Obese rats were randomly divided into 3 obese groups (OC, OI50, and OI100) of 12 rats each and lean rats served as a lean control group (LC). LC and OC were fed a control diet with 20% casein as protein source, whereas in OI50 and OI100 50% and 100% of the casein, respectively, was replaced isonitrogenously by insect meal from Tenebrio molitor L. All data were analyzed by 1-factor ANOVA, except transcriptomic data which were analyzed by groupwise comparisons with the OC group. Results Transcript profiling revealed a coordinated inhibition by −17% to −521% and −37% to −859% of genes involved in fatty acid, triacylglycerol (TG), and cholesterol biosynthesis in the livers of OI100 and OI50, respectively, compared with OC (P < 0.05). Enzyme activities of fatty acid synthase, glucose-6 phosphate dehydrogenase, and 3-hydroxy-3-methylglutaryl-coenzyme-A reductase in the liver were 100–150% greater in OC compared with LC, but reduced by 50–60% in OI100 compared with OC (P < 0.05), to the same level as in LC. Liver and plasma concentrations of TG and cholesterol were 250–1000%, 30–800%, and 40–600% higher in OC, OI50, and OI100, respectively, than in LC (P < 0.05), but 40–60% and 20–60% lower in OI100 and OI50, respectively, than in group OC (P < 0.05). Plasma and liver concentrations of homocysteine were 20–30% lower in group OI100 than in group OC (P < 0.05). Conclusion Insect meal exerts pronounced lipid-lowering effects in hyperlipidemic rats and, thus, might be useful for hyperlipidemic individuals.

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An explanation for decreased ketogenesis in the liver of the obese Zucker rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.257.4.r822 ◽

1989 ◽

Vol 257 (4) ◽

pp. R822-R828 ◽

Cited By ~ 2

Author(s):

M. J. Azain ◽

J. A. Ontko

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Rat Liver ◽

Intact Cell ◽

Zucker Rats ◽

Acid Oxidation ◽

Palmitate Oxidation ◽

Malonyl Coa ◽

Obese Zucker Rats ◽

Rat Livers

These studies were undertaken to further characterize and explain the differences in hepatic fatty acid metabolism between lean and obese Zucker rats. It was shown that the rate of palmitate or octanoate oxidation and the inhibition of palmitate oxidation by malonyl CoA in mitochondria isolated from lean and obese Zucker rats were similar. Cytochrome oxidase activity was similar in lean and obese rat livers. It was found that the addition of cytosol from the obese rat liver inhibited palmitate oxidation by 20-30% in mitochondria isolated from lean or obese rat livers and thus reproduced the conditions observed in the intact cell. Increased concentrations of metabolites such as malonyl CoA and glycerophosphate in the liver of the obese rat are likely contributors to this inhibitory effect. These results are extrapolated to the intact cell and suggest that decreased hepatic fatty acid oxidation in the obese rat can be accounted for by cytosolic influences on the mitochondria. The decreased rate of fatty acid oxidation observed in the intact hepatocyte or perfused liver cannot be explained by a defect in the capacity of mitochondria to oxidize substrate or by a decrease in mitochondrial number in the obese rat liver.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.2.r453 ◽

2000 ◽

Vol 278 (2) ◽

pp. R453-R459 ◽

Cited By ~ 17

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.

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Fatty Acid Synthase and Hormone-sensitive Lipase Expression in Liver Are Involved in Zinc-α2-glycoprotein-induced Body Fat Loss in Obese Mice

Chinese Medical Sciences Journal ◽

10.1016/s1001-9294(10)60043-0 ◽

2010 ◽

Vol 25 (3) ◽

pp. 169-175 ◽

Cited By ~ 16

Author(s):

Feng-ying Gong ◽

Jie-ying Deng ◽

Hui-juan Zhu ◽

Hui Pan ◽

Lin-jie Wang ◽

...

Keyword(s):

Fatty Acid ◽

Body Fat ◽

Fatty Acid Synthase ◽

Hormone Sensitive Lipase ◽

Obese Mice ◽

Fat Loss ◽

Hormone Sensitive ◽

Lipase Expression

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Natural conjugated linoleic acid enriched lamb meat fat modifies tissue fatty acid profile and increases n-3 HUFA score in obese Zucker rats

Proceedings of The Nutrition Society ◽

10.1017/s002966511800023x ◽

2018 ◽

Vol 77 (OCE2) ◽

Cited By ~ 1

Author(s):

G. Carta ◽

E. Murru ◽

C. Manca ◽

A. Abolghasemi ◽

A. Serra ◽

...

Keyword(s):

Fatty Acid ◽

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Fatty Acid Profile ◽

Zucker Rats ◽

Tissue Fatty Acid ◽

Lamb Meat ◽

Obese Zucker Rats

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In obese rat muscle transport of palmitate is increased and is channeled to triacylglycerol storage despite an increase in mitochondrial palmitate oxidation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90896.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. E738-E747 ◽

Cited By ~ 75

Author(s):

Graham P. Holloway ◽

Carley R. Benton ◽

Kerry L. Mullen ◽

Yuko Yoshida ◽

Laelie A. Snook ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Zucker Rats ◽

Acid Oxidation ◽

Fatty Acid Transport ◽

Acid Transport ◽

Mitochondrial Fatty Acid Oxidation ◽

Palmitate Oxidation ◽

Mitochondrial Fatty Acid ◽

Obese Zucker Rats

Intramuscular triacylglycerol (IMTG) accumulation in obesity has been attributed to increased fatty acid transport and/or to alterations in mitochondrial fatty acid oxidation. Alternatively, an imbalance in these two processes may channel fatty acids into storage. Therefore, in red and white muscles of lean and obese Zucker rats, we examined whether the increase in IMTG accumulation was attributable to an increased rate of fatty acid transport rather than alterations in subsarcolemmal (SS) or intermyofibrillar (IMF) mitochondrial fatty acid oxidation. In obese animals selected parameters were upregulated, including palmitate transport (red: +100%; white: +51%), plasmalemmal FAT/CD36 (red: +116%; white: +115%; not plasmalemmal FABPpm, FATP1, or FATP4), IMTG concentrations (red: ∼2-fold; white: ∼4-fold), and mitochondrial content (red +30%). Selected mitochondrial parameters were also greater in obese animals, namely, palmitate oxidation (SS red: +91%; SS white: +26%; not IMF mitochondria), FAT/CD36 (SS: +65%; IMF: +65%), citrate synthase (SS: +19%), and β-hydroxyacyl-CoA dehydrogenase activities (SS: +20%); carnitine palmitoyltransferase-I activity did not differ. A comparison of lean and obese rat muscles revealed that the rate of change in IMTG concentration was eightfold greater than that of fatty acid oxidation (SS mitochondria), when both parameters were expressed relative to fatty transport. Thus fatty acid transport, esterification, and oxidation (SS mitochondria) are upregulated in muscles of obese Zucker rats, with these effects being most pronounced in red muscle. The additional fatty acid taken up is channeled primarily to esterification, suggesting that upregulation in fatty acid transport as opposed to altered fatty acid oxidation is the major determinant of intramuscular lipid accumulation.

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Abnormal fatty acid utilization by cultured cardiac cells from 7-day-old obese zucker rats

Journal of Cellular Physiology ◽

10.1002/jcp.1041400307 ◽

1989 ◽

Vol 140 (3) ◽

pp. 449-454 ◽

Cited By ~ 2

Author(s):

Annie Quignard-Boulange ◽

Marianne Freyss-Beguin ◽

Lucienne Brigant ◽

Elisabeth Millanvoye-Van Brussel

Keyword(s):

Fatty Acid ◽

Cardiac Cells ◽

Zucker Rats ◽

Fatty Acid Utilization ◽

Obese Zucker Rats

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

British Journal Of Nutrition ◽

10.1017/s000711450999256x ◽

2009 ◽

Vol 103 (6) ◽

pp. 869-878 ◽

Cited By ~ 21

Author(s):

Susana V. Martins ◽

Paula A. Lopes ◽

Cristina M. Alfaia ◽

Pedro O. Rodrigues ◽

Susana P. Alves ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Acid Composition ◽

Saturated Fat ◽

Zucker Rats ◽

Adipose Tissues ◽

Obese Zucker Rats ◽

Fat Diets ◽

Pai 1

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

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