Transgenic expression of CD36 in the spontaneously hypertensive rat is associated with amelioration of metabolic disturbances but has no effect on hypertension.
Spontaneously hypertensive rats (SHR/NIH strain) harbor a deletion variant in the Cd36 fatty acid transporter and display defective fatty acid metabolism, insulin resistance and hypertension. Transgenic rescue of Cd36 in SHR ameliorates insulin resistance and improves dyslipidemia. However, the role of Cd36 in blood pressure regulation remains controversial due to inconsistent blood pressure effects that were observed with transgenic expression of Cd36 on the SHR background. In the current studies, we developed two new SHR transgenic lines, which express wild type Cd36 under the control of the universal Ef-1 alpha promoter, and examined the effects of transgenic expression of wild type Cd36 on selected metabolic and cardiovascular phenotypes. Transgenic expression of Cd36 in the new lines was associated with significantly decreased serum fatty acids, amelioration of insulin resistance and glucose intolerance but failed to induce any consistent changes in blood pressure as measured by radiotelemetry. The current findings confirm the genetic association of defective Cd36 with disordered insulin action and fatty acid metabolism in the SHR/NIH strain and suggest that Cd36 is linked to other gene(s) on rat chromosome 4 that regulate blood pressure.
Pravenec
M
M
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic. pravenec@biomed.cas.cz
Landa
V
V
Zídek
V
V
Musilová
A
A
Kazdová
L
L
Qi
N
N
Wang
J
J
St Lezin
E
E
Kurtz
T W
TW
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D019540:Area Under Curve; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D020648:Peptide Elongation Factor 1 / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D018955:CD36 Antigens; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020648:Peptide Elongation Factor 1; D005632:Fructose; D005947:Glucose