Nuclear receptors and hepatic lipidogenic enzyme response to a dyslipidemic sucrose-rich diet and its reversal by fish oil n-3 polyunsaturated fatty acids.
A sucrose-rich diet (SRD), compared with a starch diet, induces time-dependent metabolic disorders and insulin resistance with hypertriglyceridemia, similar to type 2 diabetes. In this study, we examined the effect of SRD, after 8 mo, on nuclear receptors peroxisome proliferator-activated receptor-alpha (PPARalpha), and liver X receptor-alpha (LXRalpha), stearoyl-CoA desaturase-1 (SCD-1), and Delta6 and Delta5 desaturases mRNA and activity, hepatic enzymes involved in lipid metabolism, and fatty acid (FA) composition as well as the reversal produced by cod liver oil. SRD induced triglyceride increase in plasma and liver, increasing the anabolic FA synthase, malic enzyme, and glucose-6-phosphate dehydrogenase, but not the prooxidative enzymes FA oxidase and carnitine palmitoyltransferase I, and correspondingly decreased PPARalpha and increased LXRalpha expressions. Results suggest a contribution of both nuclear receptors' interaction on these enzymatic activities. SRD depressed SCD-1 without altering oleic acid proportion and increased Delta6 and Delta5 desaturases and the proportion of n-6 arachidonic acid. Therefore, the data do not support that SRD hypertriglyceridemia is produced by increased SCD-1-dependent oleic acid biosynthesis. The administration of 7% cod liver oil for 2 mo depressed LXRalpha, enhancing PPARalpha in control and SRD-fed rats, reversing the activity of the hepatic enzymes involved in lipid metabolism and therefore the hyperlipidemia produced by the SRD. Fish oil increased n-3 PUFA and depressed n-6 PUFA of liver lipids without altering the 18:1/18:0 ratio, suggesting that its effects were produced mainly by competition of dietary n-6 and n-3 FA and not through desaturase activity modification.
Hein
Gustavo J
GJ
Departamento de Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
Bernasconi
Ana M
AM
Montanaro
Mauro A
MA
Pellon-Maison
Magali
M
Finarelli
Gabriela
G
Chicco
Adriana
A
Lombardo
Yolanda B
YB
Brenner
Rodolfo R
RR
D000818:Animals; D003060:Cod Liver Oil / Q000008:administration & dosage* / Q000737:chemistry; D019422:Dietary Sucrose / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000378:metabolism* / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*
D019422:Dietary Sucrose; D015525:Fatty Acids, Omega-3; D018160:Receptors, Cytoplasmic and Nuclear; D003060:Cod Liver Oil; D010088:Oxidoreductases