Increased survival time or better quality of life? Trade-off between benefits and adverse events in the systemic treatment of cancer.

INTRODUCTION: Primary objective of the study was to assess the relative weighting between benefit in survival time (SV), benefit in quality of life (QoL) and willingness to experience adverse events (AEs), in patient preferences for chemotherapy treatment. MATERIALS AND METHODS: We included cancer patients with current or past systemic treatment of cancer (STC) as well as physicians placed as hypothetical patients. Participants filled a choice-based conjoint analysis questionnaire with 19 choices among three STC scenarios with variable amounts of benefit in SV or QoL and different types AEs. RESULTS: One hundred patients (50 on curative and 50 on palliative intention treatment) and 114 physicians (61 oncologists and 53 non-oncologists) were included and asked about their preferred chemotherapy treatment. The relative weighting (sum 100%) of SV-QoL-AEs for making the choice in the 100 patients was SV35%-CV33%-AEs31% what was not significantly different from a random distribution (Goodness of fit Chi square P = 0.91) just as it was not for both subgroups, palliative (SV37%-QoL29%-AEs34%; GoF Chi square P = 0.55) and curative (SV34%-QoL36%-AEs30%; GoF Chi square P = 0.73) treatment. The observed distribution in the group of 114 physicians (SV46%-QoL31%-AEs23%) was significantly different from a random distribution (GoF Chi square P = 0.018) just as it was for both subgroups, medical oncologists (SV48%-QoL29%-AEs23%; GoF Chi square P = 0.006) and non-medical oncologists (SV44%-QoL33%-AEs23%; GoF Chi square P = 0.04). CONCLUSIONS: The three attributes (SV, QoL, and AEs) are considered in the same way by cancer patients to make choices on their STC. On the contrary, when placed as hypothetical patients, physicians prefer for themselves those treatments that provide more SV.

Zigzagging: theoretical insights on climbing strategies.

Human and animal trails on steep hillsides often exhibit dramatic switchbacks and shortcuts. Helbing et al. have recently examined the emergence of human trail systems on flat terrains while Minetti and Margaria established the effect of gradients on human metabolic efficiency. In this paper we use these ideas to develop a semi-quantitative theoretical model of the behaviour of humans moving on a terrain with relief. The model determines the direction of movement by minimising metabolic cost per unit of distance in a desired direction. The structure of the theory resembles the Landau Theory of Phase Transitions, much used in theoretical physics. We find that both hairpin bends (switchbacks) and shortcuts appear as efficient strategies for downhill walkers, while uphill walkers retain switchbacks. For weakly inclined slopes, the best strategy involves walking directly uphill or downhill. For sufficiently steep slopes, however, we find that the best strategy should undergo a transition to a broken symmetry solution corresponding to the switchback trail patterns typical of rugged environments. The critical slope at which this transition takes place should be less steep for uphill and downhill walkers. The theory should be amenable to empirical investigation. Amongst other applications, this model will enable us to generalize the work of previous authors to real landscapes, eventually permitting the reconstruction of ancient patterns of movement in archaeological landscapes.

Anticoagulants and other preanalytical factors interfere in plasma nitrate/nitrite quantification by the Griess method.

Nitric oxide (NO) is a signal molecule with functions such as neurotransmission, local vascular relaxation, and anti-inflammation in many physiological and pathological processes. Various factors regulate its intracellular lifetime. Due to its high reactivity in biological systems, it is transformed in the bloodstream into nitrates (NO(-)(3)) by oxyhemoglobin. The Griess reaction is a technically simple method (spectrophotometric, 540 nm) for the analysis of nitrites (NO(-)(2)) in aqueous solutions. We studied the interference of common anticoagulants in the quantification of nitrate and nitrite in plasma samples by the Griess method. We obtained rat plasma using heparin or sodium EDTA as anticoagulants, then added, or otherwise, known NO(-)(3) amounts in order to calculate their recovery. We also studied the effect of ultra-filtration performed before Griess reaction on plasma and aqueous solutions of various anticoagulants (heparin, EDTA, and also sodium citrate) to compare the recoveries of added NO(-)(3) or NO(-)(2). We used standards of NO(-)(3) or NO(-)(2) for quantification. We conclude that: (i) The bacterial nitrate reductase used to reduce NO(-)(3) to NO(-)(2) is unstable in certain storage conditions and interferes with different volumes of plasma used. (ii) The ultrafiltration (which is sometimes performed before the Griess reaction) of plasma obtained with EDTA or citrate is not recommended because it leads to overestimation of NO(minus sign)(3). In contrast, ultrafiltration is necessary when heparin is used. (iii) The absorbance at 540 nm attributed to plasma itself (basal value or background) interferes in final quantification, especially when ultrafiltration is not performed. For the quantification of plasma NO(-)(3) we recommend: sodium EDTA as anticoagulant, no ultrafiltration of plasma, and measurement of the absorbance background of each sample.

Secretion of hepatic lipase by perfused liver and isolated hepatocytes.

Hepatic lipase is found in liver and in adrenal glands and ovaries. Because in adult rats, neither adrenals nor ovaries synthesize this enzyme, it is assumed that the liver is the origin of their hepatic lipase. Our aim was to study the secretion of hepatic lipase by the liver. We observed that plasma of both fed and fasted rats contained hepatic lipase activity. This activity was significantly correlated with that in the liver. Isolated livers, perfused with heparin-free medium, secreted fully active hepatic lipase to the perfusate. The addition of heparin resulted in a rapid and larger release of hepatic lipase to the perfusate. In isolated hepatocytes, heparin did not affect the secretion of hepatic lipase mass, although it increased the stability of the enzyme activity. To study the degradation of hepatic lipase by hepatocytes, protein synthesis was blocked with cycloheximide, and both secreted and intracellular hepatic lipases were analyzed by Western blotting. We observed that the amount of hepatic lipase secreted equaled the decrease of intracellular mass. The total mass of the enzyme (inside and outside the cells) remained constant, at least for 90 min. In the next experiment, 0.7 nM 125I-hepatic lipase was added to hepatocyte suspensions, and the appearance of trichloracetic acid-soluble products was analyzed. Only 12% of the radioactivity added was associated with the cells after 90 min of incubation, and less than 2% of the hepatic lipase added was degraded. Although the association was decreased in the presence of heparin, the amount of 125I-hepatic lipase degraded was not affected. Taking all these results into account, we propose a model for the continuous secretion of hepatic lipase by the liver.

Effect of fasting on hepatic lipase activity in the liver of developing rats.

The effect of fasting on hepatic lipase was studied during postnatal development in the rat. It was found that fasting produced a significant decrease in hepatic lipase only in neonatal (1-day-old) and adult (60-day-old) rats. We studied the effect of fasting on the distribution of hepatic lipase between extracellular (heparin-releasable) and intracellular (liver-retained or residual) compartments in perfused livers, and on the secretion of hepatic lipase by isolated hepatocytes. Fasting had similar effects in neonates and adults: it decreased both the heparin-releasing and the residual activities in perfused livers, and also decreased the rate of hepatic lipase secretion by isolated hepatocytes. Finally, the effect of fasting on hepatic lipase mRNA relative abundance in developing rat livers was determined. No difference was observed among the groups studied. It is concluded that the mechanisms involved in the effect of fasting on hepatic lipase appear to be similar in neonates and adult animals and may involve the post-translational processing of the enzyme.

Effects of growth and differentiation factors on the epithelial-mesenchymal transition in cultured neonatal rat hepatocytes.

BACKGROUND/AIMS: Loss of specific differentiation markers, adoption of a migrating morphology and progressive replacement of the cytokeratin network by vimentin intermediate filaments characterize the epithelial-mesenchymal transition of cultured neonatal rat hepatocytes. In a previous study (Hepatology 1997; 25: 598-606), we reported that this process can be differentially regulated by EGF and DMSO, two agents that affect hepatocyte growth and differentiation. The aim of the present study was to determine if growth activation or differential gene expression could explain the differences in EMT observed between these two factors. METHODS: We compared the effects of EGF, HGF, TGF-beta1 and DMSO on growth, proto-oncogene expression, epithelial-mesenchymal transition markers and expression of liver transcription factors in cultured neonatal rat hepatocytes using thymidine incorporation, Northern blotting and Western blotting analysis. RESULTS: When TGF-beta1 or DMSO was added to the cultures supplemented with EGF and HGF, the mitogenic activity induced by these factors was inhibited. DMSO down-regulated c-myc and c-fos expression. mRNA levels of some liver-specific genes such as albumin, or liver-enriched transcription factors such as C/EBPdelta, HNF-4 and HNF-1beta were slightly different in cultures supplemented with DMSO or TGF-beta1. However, no differences were found when DMSO or TGF-beta1 was added to the cultures supplemented with EGF. Western blotting analysis showed that TGF-beta1 decreased cytokeratin and increased vimentin levels, while DMSO decreased both cytokeratin and vimentin. When DMSO or TGF-beta1 was added in combination with EGF or HGF, both factors maintained the increase in albumin and cytokeratin induced by the growth factors although DMSO, but not TGF-beta1, inhibited vimentin expression. CONCLUSIONS: Activation of vimentin expression produced in cultures supplemented with the mitogenic factors (EGF and HGF) is independent of the activation of cell growth, because DMSO but not TGF-beta1 can abolish vimentin synthesis, although both inhibited growth. Moreover, the vimentin expression in these cultures seems to be independent of the mRNA levels of transcription factors associated with the differentiated liver phenotype.

Acquired lipoprotein lipase deficiency associated with chronic urticaria. A new etiology for type I hyperlipoproteinemia.

Type I hyperlipoproteinemia (type I HLP) is a rare disorder of lipid metabolism characterized by fasting chylomicronemia and reduced postheparin plasma lipoprotein lipase (LPL) activity. Most cases of type I HLP are due to genetic defects in the LPL gene or in its activator, the apolipoprotein CII gene. Several cases of acquired type I HLP have also been described in the course of autoimmune diseases due to the presence of circulating inhibitors of LPL. Here we report a case of type I HLP due to a transient defect of LPL activity during puberty associated with chronic idiopathic urticaria (CIU). The absence of any circulating LPL inhibitor in plasma during the disease was demonstrated. The LPL genotype showed that the patient was heterozygous for the D9N variant. This mutation, previously described, can explain only minor defects in the LPL activity. The presence of HLP just after the onset of CIU, and the elevation of the LPL activity with remission of the HLP when the patient recovered from CIU, indicate that type I HLP was caused by CIU. In summary, we report a new etiology for type I HLP - a transient decrease in LPL activity associated with CIU and with absence of circulating inhibitors. This is the first description of this association, which suggests a new mechanism for type I HLP.

Partial hepatectomy and/or surgical stress provoke changes in the expression of lipoprotein lipase and actin in liver and extrahepatic tissues.

The expression of lipoprotein lipase (LPL) and actin genes was examined in heart, muscle and white adipose tissue (WAT) and the expression of albumin and actin genes was examined in regenerating liver after 2/3 hepatectomy. Both surgical stress and partial hepatectomy (PH) affected LPL and actin mRNA levels in muscle and WAT, but not in heart. The changes in LPL mRNA suggest transcriptional regulation of the enzyme during hepatic regeneration. Our results show for the first time that the LPL gene expression in the different tissues studied is altered not only by the surgical stress, but also by PH per se. Actin expression is also affected in some tissues. In liver, PH and surgical stress altered the expression of albumin and total mRNA. The total mRNA of the other tissues studied did not change. The changes observed in LPL in different tissues, especially in WAT and muscle, may be responsible for some of the changes in lipidic metabolism, thus allowing for some plasma lipoproteins to be used as substrates by the LPL activity that arises in the liver during hepatic regeneration. The fatty acids derived from these lipoproteins would constitute not only an energy source but also the building material needed in the process of restoration of the lost hepatic mass. It is suggested that hormonal changes taking place after surgery are responsible for the variation in the levels of the different mRNAs studied.

Circadian rhythms of lipoprotein lipase and hepatic lipase activities in intermediate metabolism of adult rat.

Although intermediate metabolism is known to follow circadian rhythms, little information is available on the variations in lipoprotein lipase (LPL) and hepatic lipase (HL) activities during the 24-h period, and there is also a lack of adequate statistical analysis. Here, adult male rats were fed ad libitum and kept at 21 degrees C under 12:12-h light-dark cycles. They were killed in batches every 3 h over a 24-h period. Lipase activities were determined in plasma and fresh homogenates of epididymal white adipose tissue (EWAT), interscapular brown adipose tissue (IBAT), heart, skeletal muscle, and liver. Plasma insulin, corticosterone, glucose, triacylglycerol (TAG), cholesterol, glycerol, beta-hydroxybutyrate, and liver and muscle glycogen were determined. Cosinor analysis was used to evaluate the presence (significance of fit of cosine curve to data and variance explained by rhythm) and characteristics of possible circadian rhythms [acrophase (phi), mesor, and amplitude]. Statistically significant circadian rhythms were detected for 1) all metabolites studied, except TAG, cholesterol, and liver HL activity; 2) LPL and HL activity in plasma (both phi in light phase); and 3) LPL activity in all tissues studied (phi: heart in light phase; skeletal muscle, IBAT, and EWAT in dark phase). Liver also showed a circadian rhythm of LPL activity, with phi near that in plasma. These findings demonstrate for the first time that, in physiological conditions, LPL activities in plasma and various tissues, including liver, and HL activity in plasma follow circadian rhythms. Their metabolic significance is discussed.

Growth and differentiation factors inhibit the migratory phenotype of cultured neonatal rat hepatocytes induced by HGF/SF.

Previous studies have demonstrated that neonatal rat hepatocytes cultured in a serum-free medium adopt a fibroblast-like morphology and form a well-developed vimentin network. By immunoblotting, phase-contrast microscopy, and immunolocalization studies we report here that hepatocyte growth factor (HGF) induces a pronounced migratory/scatter phenotype in neonatal hepatocytes in primary culture. These fibroblast-like cells are highly elongated and adopt a pronounced spindle shape in the presence of this growth factor. Most of them coexpress vimentin and cytokeratin intermediate filaments. Both EGF and TGF-beta1 also induced vimentin expression in cytokeratin-positive cells but this effect was not correlated with a change of epithelial phenotype. Only in DMSO-supplemented cultures was vimentin expression of hepatocytes inhibited and no coexpression was observed in the presence of this factor. Remarkably, the effect induced by HGF was totally inhibited when DMSO, TGF-beta1, or EGF was added to HGF-supplemented cultures. Epithelial sheets of well-defined hepatocytes were observed with these combinations although the complete epithelial morphology was achieved by combining DMSO with a growth factor. Taken together these results suggest that growth and differentiation factors modulate the migratory effect of HGF/SF in hepatocytes.

Epithelial-mesenchymal transition of cultured rat neonatal hepatocytes is differentially regulated in response to epidermal growth factor and dimethyl sulfoxide.

Neonatal rat hepatocytes cultured in the absence of added growth factors dedifferentiate by epithelial-mesenchymal transition (EMT). This involves the loss of their typical differentiation markers, the acquisition of a migrating morphology, and a change in the expression of the intermediate filament (IF) proteins. We attempted to determine whether the EMT of cultured neonatal rat hepatocytes could be modulated by factors that maintain and promote the differentiation state of adult and fetal hepatocytes such as epidermal growth factor (EGF) and dimethyl sulfoxide (DMSO). By (3H)-thymidine incorporation, Western blotting analysis, flow cytometry, and double-immunofluorescence studies, we found that both factors have marked but opposite effects on the EMT and on proliferation of neonatal liver cells. In DMSO treatment, albumin levels were higher than in the nontreated cells at all days studied. Moreover, DMSO reduced cytokeratin levels and inhibited cell proliferation, acquisition of the fibroblast-like morphology, and vimentin expression typical of the EMT. The increase in vimentin-positive cells in serum-free medium was not observed in DMSO cultures. EGF also increased albumin levels at all days studied. In contrast, EGF treatment induced hepatocyte proliferation and enhanced vimentin and cytokeratin expression. However, the increase in vimentin levels did not correlate with a significant increase in the number of vimentin-positive cells. Moreover, vimentin-positive cells in EGF treatment were also cytokeratin-positive and albumin-positive, and they maintained epithelioid morphology in spite of the vimentin network. These results indicate that EMT of cultured rat neonatal hepatocytes is differentially regulated in response to EGF and DMSO.

Hepatic regeneration induces changes in lipoprotein lipase activity in several tissues and its re-expression in the liver.

We examined the expression of lipoprotein lipase (LPL) gene and LPL activity following a two-thirds hepatectomy and during liver regeneration. In most of the tissues studied, LPL activity increased a few hours after partial hepatectomy, but soon returned to normal levels. The greatest increase was found in the adrenal glands, plasma and liver. This increase in LPL activity in the liver could be partially due to an increase in the influx of the enzyme from extrahepatic tissues. There is, however, also a re-expression of LPL mRNA in the liver after partial hepatectomy (during the first hours). It is well known that LPL is expressed in the liver of neonatal animals, but progressively decreases during post-natal development, to reach adult levels around the time of weaning. Our results show by the first time that the remaining liver re-expresses LPL gene during the regeneration process and that the hepatocytes de-differentiate and acquire some of the neonatal characteristics. The increase in LPL mRNA will contribute to the rise in LPL activity after hepatectomy. This presence of LPL could enable the liver to take up fatty acids from the circulating triacylglycerols, which are needed as energetic and plastic substrates during the process of hepatic regeneration.

Decrease in the expression of hepatic lipase activity following partial hepatectomy.

Variations in hepatic lipase (HL) activity were studied for the first time in liver, plasma and adrenal glands of partially hepatectomized (70%), sham-operated and intact rats. Activity profiles performed during 7 days in liver, plasma and adrenal glands of sham-operated rats were similar to those obtained in intact animals. However, HL activity in intact animals appeared to be slightly higher during the first 24 hours. Following surgery, hepatectomized animals showed a reduction of about 300 U in liver HL activity which persisted for 7 days. Plasma HL activity of hepatectomized rats was undetectable at 6 hours post-surgery but in increased afterwards. A high correlation between liver and adrenal gland HL activity was found in hepatectomized but not in sham-operated animals. HL mRNA levels in hepatectomized rats showed a 40% decrease during the first 24 hours after surgery, but they returned to the normal range later. On the other hand, HL mRNA values increased in sham-operated rats but no increase in HL activity was detected in these animals. To conclude, our results show that HL activity decreases dramatically during hepatic regeneration due to a concomitant decrement in the expression of the gene that encodes the enzyme and to other undetermined factors.

Vimentin filaments follow the preexisting cytokeratin network during epithelial-mesenchymal transition of cultured neonatal rat hepatocytes.

Changes in cell cytoskeleton are known to play an important role in differentiation and embryogenesis and also in carcinogenesis. Previous studies indicated that neonatal hepatocytes undergo an epithelial-mesenchymal transition when cultured in a serum-free medium for several days. Here we show by Western blotting of neonatal rat liver cells cultured for 3 days that vimentin and cytokeratin were expressed by these cells. Epidermal growth factor treatment induced high coexpression of vimentin and cytokeratin filaments in hepatocytes from neonatal livers, as detected by double immunofluorescence microscopy. Confocal scanning laser microscopy was used to determine the spatial and cell distribution of cytokeratin and vimentin intermediate filament networks. Vimentin-expressing hepatocytes were mainly located on the periphery of epithelial clusters and presented a migratory morphology, suggesting that vimentin expression was related to the loss of cell-cell contact. Short vimentin filaments were mainly located at the cytoplasmic sites behind the extending lamella. Horizontal and vertical dual imaging of double immunofluorescence with anti-vimentin and anti-cytokeratin antibodies indicated that both filaments colocalize strongly. Three-dimensional reconstruction of serial optical sections revealed that newly synthesized vimentin distributed following the preexisting cytokeratin network and, when present, both filament scaffolds codistributed inside cultured hepatocytes. Immunoelectron microscopy performed in whole-mount-extracted cultured cells revealed that both filaments are closely interrelated but independent. However, a high degree of immunogold colocalization was found in the knots of the filament network. Further experiments with colcemide and cytochalasin treatment indicated that vimentin filament distribution, but not cytokeratin, was dependent on an intact microtubule network. These results are consistent with a mechanism of vimentin assembly, whereby growth of vimentin intermediate filaments is dependent on microtubules in topographically restricted cytoplasmic sites, in close relation to the cytokeratin cytoskeleton and to changes in cell-cell contact and cell shape.

Hormonal regulation of lipoprotein lipase activity from 5-day-old rat hepatocytes.

Lipoprotein lipase (LPL) activity is known to be synthesized, active and functional in the 1-day-old rat liver: it peaks just at birth triggered by parturition. During suckling LPL mRNA, LPL synthesis and LPL activity are still high at 5 days and then fade reaching adult values at weaning. How LPL expression is gradually extinguished is not known. Therefore we studied the effect of different doses of several hormones on LPL activity released by incubated hepatocytes from 5-day-old rats. In the presence of heparin the release of LPL activity in the medium was linear until 3 h and was always significantly increased vs. without heparin. At 3 h in the presence of heparin the main hormonal effects were: dose-dependent increase (30-60%) with dexamethasone; dose-dependent increase (20-60%) with glucagon; dose-independent decrease (50-60%) with ethinylestradiol, testosterone, progesterone and prolactin; no effect with insulin; 20-40% increase with adrenaline < 1 mM but 40-50% decrease with noradrenaline < 10 microM. Increase of LPL release by glucagon and adrenaline agrees with the increased LPL expression we previously found in an undifferentiated hepatoma cell line when the adenylate cyclase/protein kinase A pathway was activated. The effect of glucagon is concordant with our previous observations that fasting increases liver LPL activity in neonatal rats. The high estradiol levels known to be present in male and female 9-19-day-old rats might contribute to liver LPL extinction during suckling.

Epithelial-mesenchymal transition in cultured neonatal hepatocytes.

When hepatocyte-enriched fractions from neonatal rat livers were cultured for different times in the absence of added growth factors, a population of highly proliferating and migrating fibroblastlike cells appeared. Double immunofluorescence with antibodies to cytokeratin and to vimentin showed a progressive reduction in the number of cytokeratin-positive cells parallel to an increase in the vimentin-positive cells. Some cells with transitional epithelial or migrating morphology coexpressed both intermediate filament proteins. Immunofluorescence with antibodies against hepatocyte differentiation markers showed that shortly after seeding most of the cells were positive to anti-albumin antibodies, but after 1 week in culture, only 10% were positive. Cells presenting albumin and cytokeratin appeared morphologically epithelial. Fibroblastlike cells were not positive for albumin, but some cells with transitional epithelial morphology presented some labels for albumin and for vimentin. Immunofluorescence with antibodies to glutathione-S-transferase subunit Pi and vimentin showed that many fibroblastlike cells were positive for both markers, some of them binucleate. Cultures performed in the presence of dexamethasone, absence of arginine, or on collagen type I matrix had no effect on the behavior of neonatal hepatocytes. The appearance of fibroblastlike cells was ontogenically regulated because the highest increase in the percentage of vimentin-positive cells was observed in cell cultures from livers of 7- and 15-day-old animals. These data provide evidence that neonatal hepatocytes in culture have the potential to dedifferentiate by epithelial-mesenchymal transition and contribute to an understanding of hepatic growth development.

Lipoprotein lipase activity in developing rat brain areas.

Lipoprotein lipase (LPL) is a key extracellular enzyme that enables tissue to import fatty acids from triacylglyceride-rich lipoproteins. LPL is present in most tissues of the body, but in the brain its functional significance remains unclear. Lipids constitute the main components of myelin and undergo significant changes during maturation. However, nothing is known of the postnatal evolution of LPL activity in the brain areas during postnatal development. Here we found that LPL activity is relatively high in the newborn brain and peaks between the 5th and the 10th days after birth, reaching activities 5 times higher than in the adult brain. In all the areas studied (olfactory bulbs, cortex, thalamus, cerebellum, hippocampus, striatum, brain-stem and spinal cord) LPL also increases sharply during postnatal development. Hippocampus shows the highest LPL activity levels, which are between 5 and 11 times higher than in the other regions. The significance of these high LPL activity levels is discussed.

Lipoprotein lipase and hepatic lipase in Wistar and Sprague-Dawley rat tissues. Differences in the effects of gender and fasting.

To evaluate the effects of strain, gender and fasting in the regulation of lipoprotein lipase (LPL) and hepatic lipase (HL) activities were measured in tissues of male and female Wistar and Sprague-Dawley rats after feeding or a 24-h starvation period. It is noteworthy that an effect of gender on LPL activity was observed in Wistar, but not in Sprague-Dawley rats, not only in the basal (fed) activity in several tissues, such as white and brown adipose tissues, heart, and brain, but also in response to fasting which affected LPL activity in brown adipose tissue, heat and lung of female but not of male Wistar rats. By contrast, HL activity in liver, plasma and adrenals of Sprague-Dawley rats was higher in females than in males. No effect of gender on HL activity was observed in Wistar rats. Our results indicate that differences exist between Wistar and Sprague-Dawley rats in the regulation of both LPL and HL. Some of the contradictory results found in the literature may be explained by the differences between rat strains and gender, as well as differences in the nutritional status of the animals.