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 Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

2015 ◽  
Vol 112 (4) ◽  
pp. 1143-1148 ◽  
Author(s):  
Daniel F. Vatner ◽  
Sachin K. Majumdar ◽  
Naoki Kumashiro ◽  
Max C. Petersen ◽  
Yasmeen Rahimi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Insulin Signaling ◽  
Plasma Fatty Acid ◽  
Hepatic Triglyceride ◽  
Triglyceride Synthesis ◽  
Hepatic Glucose ◽  
Acid Esterification ◽  
Fatty Acid Esterification

A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance—wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2′-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.

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

2009 ◽  
Vol 103 (6) ◽  
pp. 869-878 ◽  
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.

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.

Synergism between aflatoxin B1 and oxytetracycline on fatty acid esterification in isolated rat hepatocytes

1992 ◽  
Vol 61 (2-3) ◽  
pp. 159-166 ◽  
Author(s):  
Marie N. Blaude ◽  
Fabienne M. Goethals ◽  
Michel A. Ansay ◽  
Marcel B. Roberfroid
Keyword(s):  
Fatty Acid ◽  
Aflatoxin B1 ◽  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Acid Esterification ◽  
Isolated Rat ◽  
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.

scholarly journals Testes of obese rats are highly responsive to n-3 long-chain fatty acids

2011 ◽  
Vol 106 (7) ◽  
pp. 1005-1012 ◽  
Author(s):  
Miyoung Suh ◽  
Krystal J. Merrells ◽  
Amy Dick ◽  
Carla G. Taylor
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Male Reproduction ◽  
Zucker Rats ◽  
Testicular Development ◽  
Organ Weights ◽  
Obese Rats ◽  
Long Chain

The present study investigated whether fatty acid compositions of testes are affected by the obese condition and dietary n-3 long-chain fatty acid (LCFA) intake. Male lean and obese Zucker rats were fed a 15 % (w/w, total diet) fat diet containing either 0 or 5·0 % (w/w, total fatty acids) n-3 LCFA for 8 weeks. Reproductive organ weights, sperm morphology and fatty acid composition of phosphatidylcholine (PC), and phosphatidylethanolamine (PE) of testes were analysed. The obese rats had significantly (P < 0·0001) smaller epididymides and seminal vesicles, larger prostates and abundant underdeveloped testes compared with lean rats. Diet treatment did not affect the sex organ weights. The effect of genotype on fatty acid composition was minor in PC and PE except for DHA (22 : 6n-3). The n-3 LCFA diet significantly (P < 0·0001) elevated 22 : 6n-3 and reduced arachidonic acid (20 : 4n-6) and DPA (22 : 5n-6) in testicular PC and PE of lean and obese rats compared with the control diet. The acylation of dietary n-3 LCFA into 22 : 6n-3 was 2-fold higher in obese rat testes than in lean rats fed the same diet. Underdeveloped testes had 70 % less 22 : 5n-6 in PC and PE than normal-size testes. Results indicate that testicular fatty acid composition is sensitive to dietary fat modulations and especially obese rats responded more to dietary n-3 LCFA than their lean counterparts. The selective reduction in 22 : 5n-6 in underdeveloped testes indicates that 22 : 5n-6 is important in male reproduction in rats and requires further study to define the role of elongation and desaturation in testicular development.

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