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Protein Concentration in ApoE-3*Leiden Mice1
,2
* TNO-Prevention and Health, Gaubius Laboratory Leiden, 2301 CE Leiden, The Netherlands;
Department of Human Biology/NUTRIM, Maastricht University, 6200 MD Maastricht, The Netherlands;
** Departments of Cardiology and Internal Medicine and
Department of Endocrinology and Diabetes, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
2To whom correspondence and reprint requests should be addressed. E-mail: pj.voshol{at}pg.tno.nl.
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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. However, the effect of fish oil administration on preexisting insulin resistance is subject to debate. In the present study, we examined the mechanism by which fish oil affects preexisting insulin resistance. High fat diet–induced insulin-resistant ApoE*3-Leiden transgenic mice were treated for 10 wk as follows: 1) high fat diet (control group), 2) high fat diet with 3 g/100 g fish oil and 3) high fat diet but food intake restricted to 75% of the ad libitum food intake. We measured plasma glucose, insulin, free fatty acids (FFA) and triglyceride (TG) levels throughout the study. After the 10-wk dietary intervention period we performed hyperinsulinemic euglycemic analyses and measured insulin sensitivity and FFA turnover. Furthermore, we then determined the VLDL-TG production rate and TNF- protein expression in white adipose tissue (WAT). Compared with control mice, the insulin sensitivity of mice treated with fish oil was not affected, whereas it was improved (P < 0.05) for energy-restricted mice. FFA turnover was unaffected in both fish oil–treated and energy-restricted mice. Compared with controls, hepatic VLDL-TG production was lower (P < 0.05) with fish oil feeding but greater with energy restriction (P < 0.05). Interestingly, the level of TNF- protein in WAT was lower (P < 0.05) in both groups. We conclude that partial replacement of saturated fat by fish oil does not improve preexisting high fat diet-induced insulin resistance, although it lowers TNF- protein levels in WAT.
KEY WORDS: • fish oil • insulin resistance • insulin sensitivity • free fatty acid metabolism • tumor necrosis factor-
Dietary interventions with fish oil, characterized by high levels of (n-3) PUFA, protect against the development of high fat diet-induced insulin resistance (1,2). However, it is subject to debate whether fish oil treatment has an effect on preexisting insulin resistance (3,4). Thus, there might be a discrepancy between the preventive effect of fish oil on the development of insulin resistance on the one hand and the absence of an effect of fish oil on preexisting insulin resistance on the other hand.
The mechanisms involved in obesity-related insulin resistance are complex, and many factors are involved. Tumor necrosis factor (TNF)2 - appears to be one of the important mediators of obesity-related insulin resistance (5). Studies in both humans and rodents show that changes in TNF- expression levels in either blood or white adipose tissue (WAT) are correlated with changes in insulin sensitivity (6). Dietary fish oil lowers the expression of TNF- in WAT, which is associated with a protection against high fat diet–induced-insulin resistance (7). The mechanism underlying the association between TNF- expression levels and insulin resistance is unclear, but evidence is accumulating that circulating free fatty acids (FFA) may be involved. Several studies show that variations in TNF- expression in WAT correlate with plasma FFA concentration and insulin sensitivity, in both rodents (8–10) and humans (11,12). However, the effect of fish oil on the relationship between FFA metabolism and the expression of TNF- in WAT in preexisting insulin resistance is unclear.
Therefore, the aim of the present study was to evaluate the effects of fish oil on insulin resistance of glucose and FFA metabolism in a model of preexistent insulin resistance. For this purpose we induced insulin resistance by feeding ApoE*3-Leiden (E3L) mice a high fat diet for 20 wk. We used E3L mice because the lipoprotein profile in these mice closely resembles that of humans (13–16). We used a group of mice with continued high fat feeding as controls. In addition, we compared in the present study the effects of fish oil feeding with energy restriction on insulin sensitivity, FFA turnover and TNF- expression, which might include changes to restore the preexisting insulin resistant state (5,17).
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MATERIALS AND METHODS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Male E3L-mice (n = 47) generated in the animal facility of TNO-prevention and health, 
18 wk of age, were housed in a temperature-controlled room on a 12-h light:dark cycle (lights on from 0700 to 1900 h) and had free access to water and a standard mouse diet. At the age of 20 wk, they were housed individually and fed a high fat diet, in which 45.3% of the energy was derived from fat (saturated bovine fat) for a period of 20 wk, followed by a diet intervention period of 10 wk. Mice were randomly assigned to one of three dietary intervention groups. The first group (control, n = 16) was fed the same high fat diet. The second group (FO, n = 15) was fed the same high fat diet as the control group, but 3 g of fat/100 g food was replaced by fish oil. Mice in the third group were energy restricted (ER, n = 16), thereby receiving 75% of the mean ad libitum food intake of mice consuming the high fat diet. The food intake was calculated for each mouse by multiplying the mean food intake by 0.75. Both diets were manufactured by Hope Farms, Woerden, The Netherlands (Table 1).
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Blood analysis.
Blood samples were taken from all mice before they were fed the high fat diet (t = 0 wk), after 20 wk of high-fat diet feeding (t = 20) and 5 wk after the start of the diet intervention period (t = 25). Blood samples were taken from the mice by tail bleeding and collected in paraoxonized tubes [to prevent hydrolysis of the triglycerides (TG)] (18) and kept on ice. Then, the samples were centrifuged (150 x g) at 4°C for 4 min and the separated plasma was immediately assayed for glucose, free fatty acids (FFA) and TG. The remaining plasma was frozen in liquid nitrogen and stored at -20°C for later measurement of insulin.
Plasma glucose was determined by a commercially available kit (#315–500; Sigma Diagnostics, St. Louis, MO). FFA were measured enzymatically with a NEFA-C kit (Wako Chemicals, GmbH, Neuss, Germany). Concentrations of TG, corrected for free glycerol, were determined using a commercially available enzymatic kit (#2336691; Boehringer Mannheim, Mannheim, Germany). Insulin concentrations were measured by using a RIA-kit (Sensitive Rat Insulin Assay; Linco Research, St. Charles, MO).
Hyperinsulinemic euglycemic clamp analysis.
At the end of the diet intervention period, whole-body insulin sensitivity was measured in half of the mice from each experimental group during a hyperinsulinemic euglycemic clamp analysis. During this clamp analysis, FFA turnover was also determined using 3H-oleic acid (Amersham, Little Chalfont, UK). The clamp analysis was performed as described earlier (19). In short, mice that had been food deprived overnight were anesthetized and infused with 3H-oleic acid only to determine basal FFA turnover. Subsequently, insulin was infused; a variable glucose infusion was used to maintain euglycemia ( 8.0 mmol/L) and FFA turnover was measured again. At the end of the hyperinsulinemic period, blood was collected and mice were killed by cervical dislocation. The collected blood was used to measure plasma glucose, FFA and specific activity of 3H-oleic acid.
Calculations.
FFA turnover was calculated according to Voshol et al. (19). In short, FFA turnover was calculated as the ratio of the infusion rate of 3H-oleic acid (Bq) and the steady-state plasma 3H-oleic acid-specific activity (Bq/µmol FFA).
Hepatic VLDL-TG production.
At the end of the diet intervention period, hepatic VLDL-TG production rate was determined in the remaining mice from each experimental group. Therefore, mice that had been food deprived for 4 h were anesthetized (0.5 mL/kg Hypnorm; Janssen Pharmaceutica, Belgium and 12.5 mg/g midazolam; Genthon, The Netherlands) and injected intravenously with 500 mg/kg Triton WR-1339 (Sigma) using a 15 g/100 g solution in PBS. Previous studies have shown that plasma VLDL-TG clearance is completely inhibited under these circumstances (20). Blood samples were drawn at t = 0, 30, 60, 90 and 120 min after Triton injection, and plasma TG concentrations were measured at the different time points as described above. Plasma TG concentrations were related to body weight, and hepatic VLDL-TG production was calculated from the slope of the curve and expressed as µmol/(kg · h).
Hepatic sterol regulatory element binding protein (SREBP)-1c mRNA levels.
SREBP-1c is involved in the regulation of VLDL-TG production. Therefore hepatic SREBP-1c mRNA levels were measured at the end of the diet intervention period. To that end, total hepatic RNA was isolated from mice used for the measurement of hepatic VLDL-TG production rate, as described by Chomczynski and Sacchi (21) using RNA-Bee (Campro Scientific, Berlin, Germany). Single-stranded cDNA was synthesized as described by Bloks et al. (22) from 3.0 µg of RNA and subsequently subjected to PCR using a SREBP-1c–specific primer set (0.5 µL cDNA, sense primer 5'-GGA GCC ATG GAT TGC ACA TT-3', anti-sense primer 5'-CCT GTC TCA CCC CCA GCA TA-3'). Levels of cDNA were measured by real-time PCR using the ABI prism 7700-sequence detection system (Applied Biosystems, Foster City, CA). The fluorogenic probe for SREBP-1c DNA-amplification (5'-FAM-CAG CTC ATC AAC AAC CAA GAC AGT GAC TTC C-BHQ1–3'), labeled with FAM and BHQ1, was made by BioSource (Camarillo, CA). The household gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was used as an internal standard for the PCR reaction. The Ct-value (number of cycles halfway through the exponential phase) was determined and was used to calculate the relative expression level, compared with GAPDH expression.
TNF- concentration in WAT.
TNF- protein concentrations in WAT from mice used for the measurement of hepatic VLDL-TGproduction rate were measured after the diet intervention period. To measure these concentrations, homogenates of WAT were made in buffer containing protease inhibitors [(0.02 mol/L Tris-HCl (pH = 7.4), 0.25 mol/L sucrose, 1.0 mmol/L dithiothreitol, 10 mmol/L EDTA, 1.0 mmol/L benzamidine, 2.0 mg/L antipain and 2.0 mg/L leupeptin dissolved in PBS] (23). The homogenates were centrifuged at 220 x g for 10 min and the supernatant was used to determine TNF- protein concentrations, using a commercially available ELISA kit (Mouse TNF- module Set, BMS607MST; Bender MedSystems, Vienna, Austria).
Statistical analysis.
For statistical analysis, SPSS version 11 (Chicago, IL) was used. The Mann-Whitney nonparametric test for two independent samples was used to define differences between the groups of mice. Mice fed the high fat diet for 20 wk were compared with mice fed the standard diet. The criterion for significance was set at P < 0.05. Because we used the energy-restricted group as a control, we did not compare the fish oil group with the energy-restricted group.
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RESULTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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At the time the mice began to consume the high fat diet, they weighed 28.4 ± 2.0 g. During the following 20 wk, the mice gained 12 g of body weight (Fig. 1). During the 10 wk of dietary intervention, mice fed the control and fish oil diets did not change body weight (Fig. 1). As expected, mice in the energy-restricted group lost body weight (10 g) (Fig. 1).
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Hyperinsulinemic euglycemic clamp analyses.
In comparison to the control mice, the glucose infusion rate to maintain euglycemia ( 8.0 mmol/L) during the hyperinsulinemic period did not differ for the fish oil group (Table 3), whereas it was higher for the energy-restricted group.
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Hepatic VLDL-TG production.
Compared with control mice, the hepatic VLDL-TG production rate was significantly lower in fish oil–fed mice (Table 4). Concomitant with a higher plasma TG concentration, hepatic VLDL-TG production was significantly greater in energy-restricted mice than in control mice.
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Compared with controls, both the fish oil diet and energy restriction significantly reduced SREBP-1c mRNA levels in the liver (Fig. 2).
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protein levels in WAT.
Compared with control mice, TNF- protein levels in WAT were significantly lower in both fish oil–fed and energy-restricted mice (Fig. 3).
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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protein concentrations in mice with high fat diet–induced insulin resistance, and compared these effects with those induced by energy restriction. Insulin resistance was induced by a high fat, high energy diet, before fish oil and energy restriction were introduced to the mice. After 10 wk of fish oil feeding, insulin resistance was not ameliorated compared with the control mice, as indicated by the similar glucose infusion rates during the hyperinsulinemic euglycemic clamp analyses in combination with unaffected plasma glucose and insulin concentrations. In contrast, energy restriction improved insulin sensitivity, as revealed by increased glucose infusion rate in combination with decreased plasma glucose and insulin concentrations. Insulin sensitivity was improved by energy restriction, thus indicating that the high fat diet–induced insulin resistance in E3L-mice remains sensitive to manipulation and may be useful in the study of diet-induced changes in insulin sensitivity, as previously shown in our laboratory (24).
Disturbances in FFA metabolism are involved in the etiology of high fat diet–induced insulin resistance. Because fish oil is suggested to play a role in FFA metabolism, we measured plasma FFA concentrations throughout the study. After fish oil feeding, no alterations occurred in plasma FFA concentrations or FFA turnover under basal as well as hyperinsulinemic conditions compared with control mice. The observation that insulin resistance was not affected by fish oil feeding therefore seems to correspond to the unaffected FFA metabolism. On the other hand, in energy-restricted mice, no changes in plasma FFA concentrations and FFA turnover occurred compared with control mice. However, in contrast to fish oil–fed mice, insulin sensitivity was improved significantly in ER-mice. Because we determined only whole-body FFA turnover, we can not exclude alterations in whole-body fatty acid (FA) oxidation. Tucker et al. (25) showed increased whole-body FA oxidative disposal and improved insulin sensitivity during hyperinsulinemic euglycemic clamp analysis after energy restriction. Therefore, we speculate that whole-body FA oxidation of energy-restricted mice is increased, thus ameliorating insulin resistance. In our study we measured only baseline and maximally insulin-suppressed FA turnover, and did not measure submaximal insulin-suppressed FA turnover. Therefore, we cannot rule out alteration in FA turnover under conditions with submaximal insulin concentrations.
Fish oil has a profound effect on hepatic VLDL-TG production. We determined hepatic VLDL-TG production after 10 wk of fish oil consumption. As shown by van Vlijmen et al. (26), the hepatic VLDL-TG production rate was decreased after fish oil feeding also under high fat feeding conditions. The decreased VLDL-TG production rate after fish oil feeding can be explained at least in part by the observed decrease in mRNA levels of SREBP-1c in the liver. SREBP-1c expression plays an important role in regulation of hepatic VLDL-TG production (27). A similar observation was made by Kim et al. (28), showing that the effect of fish oil on SREBP-1c is independent of the activating effect of fish oil on peroxisome proliferator-activated receptor (PPAR). Activation of PPAR may enhance hepatic FA oxidation, resulting in the formation of ketone bodies. Although we cannot rule out that fish oil in our study affected hepatic FA oxidation, we did not observe increased plasma ketone bodies (data not shown). This decreased hepatic VLDL-TG production rate in fish oil fed mice did not greatly decrease plasma TG concentration. Steady-state plasma TG concentrations are the result of hepatic production and plasma clearance. Previously, we observed that plasma VLDL-TG clearance increased in E3L mice fed a fish oil, Western-type diet (26). We cannot exclude that the plasma clearance of VLDL-TG was hampered in high fat/fish oil–fed mice. In contrast to fish oil feeding, energy restriction increased VLDL-TG production, accompanied by higher concentrations of plasma TG. A possible explanation is an increased supply of fatty acids, from a higher rate of lipolysis in adipose tissue, reaching the liver. Further studies should determine TG metabolism in energy-restricted mice.
Studies showing a reduction in the development of insulin resistance due to fish oil feeding usually also show decreases in plasma concentrations of TG and/or FFA (29–31). In our study, fish oil feeding did change TG metabolism by lowering hepatic VLDL-TG production but did not affect FFA metabolism. Whole-body FFA metabolism did not change in energy-restricted mice, showing that tissue/cell-specific changes are important in determining insulin sensitivity because energy-restricted mice had improved insulin sensitivity. Some studies of preexisting insulin resistance showed that fish oil feeding ameliorates insulin resistance (32,33). But in those studies, the amount of fish oil in the diet was higher (7–14 g/100 g) compared with the amount used in our study (3 g/100 g); therefore, the results of these studies are difficult to compare with our results.
TNF- is part of a wide spectrum of factors relating obesity to insulin resistance. Because fish oil has been found to lower TNF- expression, thereby affecting lipid/FFA metabolism and ameliorating insulin resistance, (1,2,7,34), we questioned whether fish oil would affect TNF- protein levels in mice with preexisting insulin resistance. After 10 wk of fish oil feeding, TNF- protein concentration decreased in WAT, although body weight was not affected by fish oil feeding. For the energy-restricted mice, we found similar effects on TNF- protein levels in WAT. But in contrast to fish oil–fed mice, the body weight of energy-restricted mice decreased during the 10-wk diet intervention period. This decrease in body weight was due mainly to a decrease in fat mass, probably due to increased adipose tissue lipolysis. This is in line with the correlation between adipose tissue mass and TNF- expression in WAT (5,17).
Because fish oil–fed mice did not lose body weight, as occurred in energy-restricted mice, fish oil apparently reduces TNF- protein independently of reduced adipose tissue mass. This is in line with a study performed in diabetic Zucker fa/fa rats (35). Interestingly, we showed that under conditions of preexisting insulin resistance, fish oil feeding can decrease TNF- expression without affecting FFA metabolism or insulin resistance. The effects on energy-restricted mice indicate that in addition to lowering TNF- expression in WAT, energy restriction elicits mechanisms different from those produced by fish oil feeding, such as increased whole body FA oxidation, ultimately resulting in ameliorated insulin resistance.
We conclude that in the presence of insulin resistance, fish oil cannot reverse high fat diet– induced insulin resistance or affect FFA metabolism, at least in mice, although it decreases TNF- levels in WAT. This has relevance for the use of fish oil–rich diets in humans because human studies have shown that fish oil does not improve insulin resistance during high fat intake (36). Fish oil supplements might be useful in the prevention of insulin resistance, but are not an effective treatment for preexisting insulin resistance.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: E3L, apolipoprotein E3-Leiden; ER, energy restriction; FA, fatty acids; FFA, free fatty acids, FO, fish oil; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PPAR, peroxisome proliferator-activated receptor; SREBP, sterol regulatory element binding protein; TG, triglycerides; TNF, tumor necrosis factor; WAT, white adipose tissue.
Manuscript received 11 June 2003. Initial review completed 16 July 2003. Revision accepted 12 August 2003.
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LITERATURE CITED |
|---|
|
TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Storlien, L. H., Kraegen, E. W., Chisholm, D. J., Ford, G. L., Bruce, D. G. & Pascoe, W. S. (1987) Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science (Washington, DC) 237:885-888.
2. Dagnelie, P. C., Rietveld, T., Swart, G. R., Stijnen, T. & van den Berg, J. W. (1994) Effect of dietary fish oil on blood levels of free fatty acids, ketone bodies and triacylglycerol in humans. Lipids 29:41-45.[Medline]
3. Podolin, D. A., Gayles, E. C., Wei, Y., Thresher, J. S. & Pagliassotti, M. J. (1998) Menhaden oil prevents but does not reverse sucrose-induced insulin resistance in rats. Am. J. Physiol. 274:R840-R848.
4. Malasanos, T. H. & Stacpoole, P. W. (1991) Biological effects of omega-3 fatty acids in diabetes mellitus. Diabetes Care 14:1160-1179.[Abstract]
5. Kern, P. A., Saghizadeh, M., Ong, J. M., Bosch, R. J., Deem, R. & Simsolo, R. B. (1995) The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J. Clin. Investig. 95:2111-2119.
6. Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L. & Spiegelman, B. M. (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J. Clin. Investig. 95:2409-2415.
7. Endres, S., Ghorbani, R., Kelley, V. E., Georgilis, K., Lonnemann, G., van der Meer, J. W., Cannon, J. G., Rogers, T. S., Klempner, M. S. & Weber, P. C. (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N. Engl. J. Med. 320:265-271.[Abstract]
8. Uysal, K. T., Wiesbrock, S. M., Marino, M. W. & Hotamisligil, G. S. (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature (Lond.) 389:610-614.[Medline]
9. Evans, R. D., Ilic, V. & Williamson, D. H. (1992) Acute administration of tumour necrosis factor-alpha or interleukin-1-alpha does not mimic the hypoketonaemia associated with sepsis and inflammatory stress in the rat. Clin. Sci. (Lond.) 82:205-209.[Medline]
10. Zhang, H. H., Halbleib, M., Ahmad, F., Manganiello, V. C. & Greenberg, A. S. (2002) Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 51:2929-2935.
11. Starnes, H. F. J., Warren, R. S., Jeevanandam, M., Gabrilove, J. L., Larchian, W., Oettgen, H. F. & Brennan, M. F. (1988) Tumor necrosis factor and the acute metabolic response to tissue injury in man. J. Clin. Investig. 82:1321-1325.
12. Van der Poll, T., Romijn, J. A., Endert, E., Borm, J. J., Buller, H. R. & Sauerwein, H. P. (1991) Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. Am. J. Physiol. 261:E457-E465.
13. van den Maagdenberg, A. M., Hofker, M. H., Krimpenfort, P. J., de Bruijn, I., van Vlijmen, B., van der Boom, H., Havekes, L. M. & Frants, R. R. (1993) Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. J. Biol. Chem. 268:10540-10545.
14. Havekes, L. M., van Vlijmen, B. J., Jong, M. C., van Dijk, K. W. & Hofker, M. H. (1997) Use of transgenic mice in lipoprotein metabolism and atherosclerosis research. Prostaglandins Leukot. Essent. Fatty Acids 57:463-466.[Medline]
15. van Vlijmen, B. J., van den Maagdenberg, A. M., Gijbels, M. J., van der Boom, H., HogenEsch, H., Frants, R. R., Hofker, M. H. & Havekes, L. M. (1994) Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. J. Clin. Investig. 93:1403-1410.
16. van Vlijmen, B. J., Pearce, N. J., Bergo, M., Staels, B., Yates, J. W., Gribble, A. D., Bond, B. C., Hofker, M. H., Havekes, L. M. & Groot, P. H. (1998) Apolipoprotein E*3-Leiden transgenic mice as a test model for hypolipidaemic drugs. Arzneimittelforschung 48:396-402.[Medline]
17. Raina, N., Lamarre, J., Liew, C. C., Lofti, A. H. & Jeejeebhoy, K. N. (1999) Effect of nutrition on tumor necrosis factor receptors in weight-gaining and -losing rats. Am. J. Physiol. 277:E464-E473.[Medline]
18. Zambon, A., Hashimoto, S. I. & Brunzell, J. D. (1993) Analysis of techniques to obtain plasma for measurement of levels of free fatty acids. J. Lipid Res. 34:1021-1028.[Abstract]
19. Voshol, P. J., Jong, M. C., Dahlmans, V. E., Kratky, D., Levak-Frank, S., Zechner, R., Romijn, J. A. & Havekes, L. M. (2001) In muscle-specific lipoprotein lipase-overexpressing mice, muscle triglyceride content is increased without inhibition of insulin-stimulated whole-body and muscle-specific glucose uptake. Diabetes 50:2585-2590.
20. Aalto-Setala, K., Fisher, E. A., Chen, X., Chajek-Shaul, T., Hayek, T., Zechner, R., Walsh, A., Ramakrishnan, R., Ginsberg, H. N. & Breslow, J. L. (1992) Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles. J. Clin. Investig. 90:1889-1900.
21. Chomczynski, P. & Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156-159.[Medline]
22. Bloks, V. W., Plosch, T., van Goor, H., Roelofsen, H., Baller, J., Havinga, R., Verkade, H. J., van Tol, A., Jansen, P. L. & Kuipers, F. (2001) Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice. J. Lipid. Res. 42:41-50.
23. Fredrikson, G., Stralfors, P., Nilsson, N. O. & Belfrage, P. (1981) Hormone-sensitive lipase from adipose tissue of rat. Methods Enzymol 71:636-646.
24. Muurling, M., Jong, M. C., Mensink, R. P., Hornstra, G., Dahlmans, V. E., Pijl, H., Voshol, P. J. & Havekes, L. M. (2002) A low-fat diet has a higher potential than energy restriction to improve high-fat diet-induced insulin resistance in mice. Metabolism 51:695-701.[Medline]
25. Tucker, M. Z. & Turcotte, L. P. (2002) Brief food restriction increases FA oxidation and glycogen synthesis under insulin-stimulated conditions. Am. J Physiol. 282:R1210-R1218.
26. van Vlijmen, B. J., Mensink, R. P., van ’t Hof, H. B., Offermans, R. F., Hofker, M. H. & Havekes, L. M. (1998) Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice. J. Lipid Res. 39:1181-1188.
27. Shimano, H. (2002) Sterol regulatory element-binding protein family as global regulators of lipid synthetic genes in energy metabolism. Vitam. Horm. 65:167-194.[Medline]
28. Kim, H. J., Takahashi, M. & Ezaki, O. (1999) Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mrnas. J. Biol. Chem. 274:25892-25898.
29. Simoncikova, P., Wein, S., Gasperikova, D., Ukropec, J., Certik, M., Klimes, I. & Sebokova, E. (2002) Comparison of the extrapancreatic action of gamma-linolenic acid and n-3 PUFAs in the high fat diet-induced insulin resistance. Endocr. Regul. 36:143-149.[Medline]
30. Otto, D. A., Baltzell, J. K. & Wooten, J. T. (1992) Reduction in triacylglycerol levels by fish oil correlates with free fatty acid levels in ad libitum fed rats. Lipids 27:1013-1017.[Medline]
31. Chicco, A., D’Alessandro, M. E., Karabatas, L., Gutman, R. & Lombardo, Y. B. (1996) Effect of moderate levels of dietary fish oil on insulin secretion and sensitivity, and pancreas insulin content in normal rats. Ann. Nutr. Metab. 40:61-70.[Medline]
32. Peyron-Caso, E., Taverna, M., Guerre-Millo, M., Veronese, A., Pacher, N., Slama, G. & Rizkalla, S. W. (2002) Dietary (n-3) polyunsaturated fatty acids up-regulate plasma leptin in insulin-resistant rats. J. Nutr. 132:2235-2240.
33. Soria, A., Chicco, A., Eugenia, D. M., Rossi, A. & Lombardo, Y. B. (2002) Dietary fish oil reverse epididymal tissue adiposity, cell hypertrophy and insulin resistance in dyslipemic sucrose fed rat model small star, filled. J. Nutr. Biochem. 13:209-218.[Medline]
34. Roche, H. M. & Gibney, M. J. (1995) Postprandial triacylglycerolaemia–nutritional implications. Prog. Lipid Res. 34:249-266.[Medline]
35. Okuno, A., Tamemoto, H., Tobe, K., Ueki, K., Mori, Y., Iwamoto, K., Umesono, K., Akanuma, Y., Fujiwara, T., Horikoshi, H., Yazaki, Y. & Kadowaki, T. (1998) Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J. Clin. Investig. 101:1354-1361.[Medline]
36. Vessby, B., Unsitupa, M., Hermansen, K., Riccardi, G., Rivellese, A. A., Tapsell, L. C., Nalsen, C., Berglund, L., Louheranta, A., Rasmussen, B. M., Calvert, G. D., Maffetone, A., Pedersen, E., Gustafsson, I. B. & Storlien, L. H. (2001) Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia 44:312-319.[Medline]
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V. van Weel, M. de Vries, P. J. Voshol, R. E. Verloop, P. H.C. Eilers, V. W.M. van Hinsbergh, J. H. van Bockel, and P. H.A. Quax Hypercholesterolemia Reduces Collateral Artery Growth More Dominantly Than Hyperglycemia or Insulin Resistance in Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1383 - 1390. [Abstract] [Full Text] [PDF]
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