Characterization of Fatty Acid Profile in the Liver of SHR/NDmcr-cp (cp/cp) Rats, a Model of the Metabolic Syndrome

Abstract

The fatty acid profile of hepatic lipid in spontaneously hypertensive rats (SHR)/NDmcr-cp (cp/cp) rats (SHR/NDcp), which offer an animal model of the metabolic syndrome, was characterized by comparing those in Wistar Kyoto rats (WKY), SHR, stroke-prone spontaneously hypertensive rats (SHRSP) and SHR/ NDmcr-cp ( / ) rats (SHR/ND ) . Hierarchical clustering analysis revealed that SHR/NDcp and the other four strains and/or substrains of rats were clearly disparate in fatty acid profile of hepatic lipid and that the disparity observed was due to the drastic increases in the mass of monounsaturated fatty acids, especially palmitoleic acid and oleic acid, in the liver of SHR/NDcp. Activities of stearoyl-CoA desaturase (SCD) and palmitoyl-CoA chain elongase in hepatic microsomes of SHR/NDcp were markedly higher than those of WKY, SHR, SHRSP and SHR/ND . Activities of palmitoleoyl-CoA chain elongase in the liver of SHR/ NDcp were also higher, but to a lesser extent. mRNA levels of SCD1 and elongation of very long-chain fatty acids (Elovl6), but not Elovl5, in the liver of SHR/NDcp were remarkably higher than those of the other four groups of rats. These results suggest that the enhanced expressions of SCD1 and Elovl6 induced abnormalities in fatty acid profile in the liver of SHR/NDcp. Key words fatty acid profile; palmitoleic acid; oleic acid; liver; SHR/NDmcr-cp (cp/cp) rat Obesity, hypertension, hyperlipidemia and hyperglycemia are risk factors for cardiovascular diseases. Patients who have two or more of these risk factors are susceptible to cardiovascular diseases; these states are called the metabolic syndrome. To explore protection against and treatment of the metabolic syndrome, studies on the pathophysiology and metabolic consequences of the metabolic syndrome are required using pertinent animal models. Spontaneously hypertensive rats (SHR)/NDmcr-cp (cp/cp) rats (SHR/NDcp) spontaneously develop obesity and hypertension, and display dyslipidemia and hyperglycemia, the values of body weight, systolic blood pressure, serum triglyceride and blood glucose in SHR/NDcp being 1.43, 1.65, 25.4 and 1.25 times, respectively, compared with those in Wistar Kyoto rats (WKY) (control rats) at 19 or 20 weeks of age.1) Thus, they provide a useful model of the metabolic syndrome.2,3) Hypertensive rats that spontaneously developed as a colony from normotensive WKY, were named SHR.4) By crossing SHR with Sprague-Dawley (SD) rats, obese spontaneously hypertensive rats, Koletsky strain, were obtained; this strain of rats is heterozygous for the cp gene.5) To eliminate the noncorpulent genes of the Koletsky strain, the rats were mated with SHR, and a congenic rat strain (SHR/National Institutes of Health (NIH)-corpulent) was developed.6) SHR/NDcp are a substrain of SHR/NIHcorpulent rats. With regard to metabolic abnormalities as to hypertension, hyperinsulinemia and hyperglycemia in SHR/ NDcp, many studies have been conducted. On the other hand, information on dyslipidemia in SHR/NDcp is very limited.

Increased Lipid Synthesis and Decreased β‐Oxidation in the Liver of SHR/NDmcr‐cp (cp/cp) Rats, an Animal Model of Metabolic Syndrome

“…Moreover, the increased gene expression of LPK suggests that the supply of acetyl-CoA from glucose is also increased in hepatocytes of SHR/NDcp. These results, taken together, strongly imply the increased formation of 16:0 in the liver of SHR/NDcp, a suggestion that is consistent with the previous finding that the liver of SHR/ NDcp contains 16:0 in large quantities [12]. Moreover, the 16:0 produced by FAS may be converted to palmitoyl-CoA by microsomal ACSL, the activity of which in the liver of SHR/NDcp was higher.…”

“…rats (SHR/ND?) (lean hypertensive littermates of SHR/NDcp), and demonstrated that SHR/NDcp and the other four strains and/or substrains of rats were clearly disparate in terms of fatty acid profile [12]. This disparity was due to drastic increases in the mass of palmitic (16:0), oleic (18:1n-9), palmitoleic (16:1n-7), cis-vaccenic (18:1n-7) and 5,8,11eicosatrienoic (20:3n-6) acids in the liver of SHR/NDcp.…”

Early Life Stress Interacts with the Diet Deficiency of Omega-3 Fatty Acids during the Life Course Increasing the Metabolic Vulnerability in Adult Rats

“…Palmitoleic acid is associated with increased insulin concentrations [55] and resistance [56] [57] [58] [59] [60] [61] [62], type II diabetes [63] [64], metabolic syndrome [61] [65] [66], heart failure [67] and coronary heart disease [68]. Plasma palmitoleic acid content is an independent marker of both triglyceridemia and abdominal adiposity in men [62] [69], which agrees with the positive correlation between this fatty acid peripheral level and the amount of abdominal fat deposition found in this study.…”

Fatty Liver Is Associated with Transcriptional Downregulation of Stearoyl-CoA Desaturase and Impaired Protein Dimerization

“…Indeed, there is scarce information about this issue; nevertheless a previous work reported that a SHR/NIH corpulent rat substrain (SHR/NDcp), which was obtained by crossing SHR/NIH corpulent rat with SHR, shows 5.5 times higher scd1 gene expression than that of WKY but also showed a tendency of the original SHR strain to have decreased levels of Scd1 expression in comparison with WKY rats [28]. …”