Plasma lipids and other factors in the LA/N corpulent rat in the presence of chronic exercise and food restriction

The effects of regular exercise and food restriction were studied in the LA/N corpulent rat up to age 9 months. This congenic strain of the Lister and Albany rat is normotensive, corpulent, and hyperlipidemic when homozygous for the corpulent (cp) gene derived from the Koletsky strain. Food restriction of corpulent animals to the intake of matched lean rats caused body weight to be significantly lower, although not as low as that of the lean animals. Plasma total cholesterol in freely eating sedentary corpulent animals was significantly higher (210 mg/100 mL) than in food-restricted rats (165 mg/100 mL), in which plasma cholesterol was considerably elevated compared with lean rats (80 mg/100 mL). Exercise caused a modest but significant increase in both total and high density lipoprotein cholesterol in both corpulent and lean rats. The rise was greater in corpulent rats and, in food-restricted exercising corpulent rats, the cholesterol concentrations were equivalent to those of freely eating corpulent animals. Systolic blood pressure in lean rats fell slowly from 146 mmHg at 8 weeks to 132 mmHg at 36 weeks and was not affected by exercise. Sedentary corpulent rats showed a rapid rise in systolic pressure from 107 mmHg at 7 weeks to 128 mmHg at 11 weeks. This rise was reduced by food restriction and completely prevented by the combination of food restriction and exercise. Thus, in this strain of rats exercise was associated with higher plasma cholesterol concentrations, while food restriction had limited effects.     

Caffeine and ephedrine stimulated thermogenesis in LA-corpulent rats

Resting metabolic rate (RMR), as well as caffeine (CAF) and ephedrine (EPH) stimulated thermogenesis (VO2) were measured in young adult corpulent (corp) LA/N-cp (LA-corpulent) rats. RMR of lean was greater than corp. Administration of EPH, CAF and EPH + CAF resulted in 32, 48 and 50% increases in VO2, respectively, in both lean and corp rats. The time to attain maximal VO2 was similar for both drugs in both phenotypes, but the duration of maximal VO2 averaged 50, 26 and 42% longer in corp than lean for EPH, CAF and EPH + CAF, respectively. Acute weight loss following these treatments was greater for corp than lean, and corresponded with the duration of elevated VO2. These results are consistent with a normally functioning end-organ sympathomimetic receptor system in the corp phenotype of the LA/N-cp rat, and suggest that obesity in this model may be caused by factors other than defective brown fat thermogenesis at the end organ level.     

Non-shivering thermogenesis and obesity in adult diabetic Wistar fatty rats

1. Characteristics of resting and of norepinephrine (NE)-stimulated thermogenesis, and the glycemic response to NE were determined in adult male Wistar Fatty rats. Rats were maintained on Purina chow No. 5001 until 22 weeks of age, and fed semisynthetic diets containing 54% carbohydrate, 20% protein, 16% mixed fats, plus essential vitamins, minerals, and non-nutritive fiber from 22 until 30 weeks of age. 2. Obese rats were 50% heavier than lean throughout the study. Phenotype effects (obese greater than lean) were present for retroperitoneal (RP) and dorsal (DOR) white fat depot weight, adipocyte number per depot, and adipocyte lipid content. Epididymal mass and cellularity were similar in both phenotypes. 3. Interscapular brown adipose tissue (IBAT) mass, adipocyte size, and adipocyte number were greater in obese than in lean. Resting metabolic rates (RMR) of obese rats were lower than in lean, and increased 79% in lean but only 33% in obese animals following NE (200 micrograms/kg BW, s.c.) stimulation. 4. The glycemic response to NE occurred normally in both phenotypes, and resulted in a 3-fold increment in plasma glucose in lean rats and a 5-6-fold increase in plasma glucose in obese rats. 5. The results of this study are consistent with hyperplasia and hypertrophy of IBAT, RP and DOR depots, and indicate that the capacity for non-shivering thermogenesis is impaired in the obese phenotype of this strain in spite of peripheral sensitivity to NE and greater mass and cellularity of brown adipose tissue.     

Effects of dietary carbohydrate and phenotype on thyroid hormones and brown adipose tissue locularity in adult LA/N-cp rats

1. Groups of lean and corpulent LA/N-cp rats were fed isoenergetic diets containing, 54% carbohydrate as maize starch (MS) or sucrose (SU), 20% protein, 16% mixed fats, plus other essential nutrients and fiber from 1.5-9 months of age. Final body weights of corpulent rats were 2-3 times those of their lean littermates, and were greater with SU than MS diet in both phenotypes. 2. Interscapular brown adipose tissue (IBAT) mass was greater in corpulent than lean and was greater with SU than MS diet in lean but not corpulent rats. IBAT cell diameters and adipocyte volumes were generally similar in both phenotypes, and were not markedly affected by dietary carbohydrate type. 3. Brown adipocyte locularity profiles were qualitatively similar in both phenotypes, and were morphologically indicative of thermogenic activity in both phenotypes. Locule profiles of corpulent animals contained a greater proportion of thermogenically less active types IV and V brown adipocytes than similarly fed lean animals, however, and locule distribution profiles were not influenced by diet. 4. Serum T3 concentrations were similar in both phenotypes, were greater in SU than MS lean rats and were not influenced by diet in the corpulent phenotype. In contrast, serum thyroxine concentrations and percent thyroxine uptake were not influenced by diet or phenotype. 5. These results are consistent with a partial impairment in BAT-mediated thermogenic activity in the corpulent phenotype and suggest that obesity in this strain may be due to factors other than biochemically defective brown adipose tissue thermogenesis.     

Impaired activation of thermogenesis in the corpulent rat

The capacity for non-shivering thermogenesis was measured in groups of 12 week-old congenic lean and corpulent LA/N-cp rats of both sexes to determine if their obese state might be associated with an impairment in energy expenditure via non-shivering thermogenesis. Body weights of the corpulent phenotypes were 1.6 to 1.8 times greater than those of the lean phenotype. Measurements of resting oxygen consumption were similar in lean and in corpulent rats, and were greater in female than in male rats. Isoproterenol stimulation resulted in a significant increase in oxygen consumption in lean rats, while the rates of oxygen consumption of isoproterenol-stimulated corpulent rats were unchanged. Acute exposure of male rats to a 5 degrees C cold environment resulted in significant decreases in colonic and in rectal temperature in both phenotypes, but body temperatures recovered more rapidly in lean than in corpulent rats. Urinary VMA excretion was greater in lean than in corpulent rats and increased following cafeteria-feeding in lean but not in corpulent rats. These observations are consistent with an impaired mechanism of sympathetically-mediated thermogenesis in the corpulent phenotype of the LA/N-cp rat, and which may be a contributing factor in the development of their obese state via a decreased capacity for energy expenditure.     

Effects of dietary carbohydrate and phenotype on adipose cellularity in female SHR/N-cp rats.

1. Adipose mass and cellularity were studied in congenic female SHR/N-cp rats fed iosenergetic diets containing 54% carbohydrate as sucrose (SU) or cooked cornstarch (CS), 20% protein, 16% mixed dietary fat plus vitamins, minerals, and non-nutritive fiber ad libitum from 5 weeks until 8.5 months of age. Measures of adipocyte lipid content, cell number per depot, and mass of principal white (WAT) and interscapular brown (IBAT) adipoe tissue depots were determined at the end of the study. 2. Final body weights (BW) of corpulent rats were more than twice those for their lean littermates, and were greater when fed the SU than the CS diet in both phenotypes. Phenotype effects (corpulent greater than lean) were present for fat pad weight, adipocyte number, and adipocyte lipid content in the dorsal (DOR) and retroperitoneal (RP) WAT depots. Diet effects were present for depot weight, adipocyte number, and adipocyte lipid content in both WAT depots, and were of qualitatively similar magnitude in both phenotypes. 3. IBAT weights, IBAT:BW ratios, and IBAT cell number of corpulent greater than lean, and were greater than with SU than CS diet in both phenotypes. 4. These results indicate that obesity in the corpulent phenotype of the SHR/N-cp rat occurs as the result of hypertrophy and hyperplasia of white adipose tissue, and that isoenergetic substitution of simple for complex carbohydrate resulted in greater fat accretion in both phenotypes. The greater diet and phenotype-associated adiposity occurred despite greater mass and cellularity of BAT. The results also indicate that sexual dimorphism occurs regarding effects of diet and phenotype on expression of adipose tissue development in this strain.     

Effect of dietary carbohydrates on insulin and glucagon receptors in a new model of noninsulin-dependent diabetes-SHR/N-corpulent rat

A new congenic strain of rat, the SHR/N-corpulent, provides a good model for noninsulin-dependent diabetes and was used in the present study. Corpulent rats as compared to their lean littermates are obese, hyperlipidemic, and severely hyperinsulinemic, and show an age-dependent loss of glucose tolerance. Mild fasting hyperglycemia is seen only in corpulent rats fed sucrose. Since dietary sucrose is more lipogenic than starch and since insulin and glucagon are involved in lipid and carbohydrate metabolism, we studied the effect of the type of dietary carbohydrate on insulin and glucagon levels and their receptors in lean and corpulent SHR/N rats. A significant phenotypic effect was observed (corpulent greater than lean) on plasma levels of triglyceride, cholesterol, and insulin. Dietary sucrose increased these parameters in corpulent rats but not in lean rats. Insulin and glucagon binding to liver plasma membranes was lower in corpulent rats than in lean; decreases were due to fewer receptors without a significant change in affinity. Thus, in corpulent rats, in addition to hyperinsulinemia, fewer glucagon receptors and their failure to be regulated by plasma glucagon levels appear to contribute to the hyperlipidemia. Furthermore, the hyperglycemia observed in sucrose-fed corpulent rats may be due to extreme resistance to insulin despite lower plasma glucagon and fewer glucagon receptors.     

Effect of age on serum lipids and lipoproteins of male and female JCR:LA-corpulent rats

The JCR:LA-cp rat is a strain incorporating the corpulent (cp) gene. When homozygous for the cp gene, the rats are hyperphagous, hyperinsulinemic, hyperlipidemic and obese. The corpulent male rats develop atherosclerotic and myocardial lesions from an early age, while corpulent female and lean rats do not develop lesions. The hyperlipidemia is due to elevated levels of VLDL resulting in moderately raised cholesterol levels and markedly elevated triacylglycerol levels. The VLDL concentrations are similar in corpulent male and female rats at an early age with both having much higher levels than lean rats. As the animals age, the VLDL hyperlipidemia in the corpulent male increases at 3 months and then decreases slowly and rises again at 12 months of age. The corpulent female rats show higher triacylglycerol and phospholipid concentrations than the males at 3 months age and reach values over 1000 mg/100 ml by 9 months of age, then decrease at 12 months of age. The cholesterol concentrations of the corpulent females are greater than those of the males from 9 months of age. Thus, in the period of life up to middle age, the cardiovascular disease incidence does not correlate with the degree of hyperlipidemia. The disease progression does correlate with the severity of insulin resistance and glucose intolerance, which is more severe in the corpulent male than female rats. The results suggest that the hyperlipidemia must be a necessary condition for development of atherosclerotic disease in this strain of rats, but it is not a sufficient condition.     

Genetic obesity and dietary sucrose decrease hepatic glucagon and insulin receptors in LA/N-corpulent rats

A catabolic and hypolipemic effect of glucagon has been described in normal animals. We therefore studied the role of glucagon in genetically obese, hyperlipemic rats. Twelve genetically obese hyperlipemic LA/N-cp/cp (corpulent) rats and 12 lean littermates were fed either 54% starch or 54% sucrose for 12 weeks. Plasma glucagon and insulin levels and glucagon and insulin binding to liver membranes were measured. Comparing all corpulent and lean animals regardless of diet, a significant (P less than 0.0001) phenotypical effect (cp/cp greater than lean) was observed in plasma insulin levels (464 +/- 54 vs 70.3 +/- 7.6 muu/ml, mean +/- SEM). Insulin binding (2.68 vs 16.1%/50 micrograms protein) and glucagon binding (25.6 vs 47.3%/50 micrograms protein) were both significantly lower (P less than 0.0001) in corpulent rats as compared to their lean littermates. Sucrose feeding had marginal effect on plasma insulin or insulin binding. It, however, decreased glucagon binding in corpulent rats but not in their controls. A significant negative correlation was observed between plasma insulin and insulin binding, while a positive correlation was seen for plasma glucagon and glucagon binding. A significant negative correlation was observed between plasma glucagon and lipogenic enzymes (glucose-6-phosphate dehydrogenase and malic enzyme) in liver and between glucagon binding and these enzymes. We propose that in these genetically obese rats, in addition to hyperinsulinemia, impaired glucagon activity as manifested by decreased glucagon binding to target cells may be an important contributor to the hyperlipemia and obesity. A further decrease in glucagon binding in rats fed sucrose indicates that sucrose, per se, may be an additional contributory factor.     

Effects of increased energy expenditure on weight gain and adiposity in the LA-corpulent rat

Groups of lean or pre-obese LA/N-cp rats were subjected to a program of vigorous exercise (less than 4 hr/day) or remained sedentary from 6 weeks until 12 weeks of age. Sedentary pre-obese rats gained weight twice as rapidly as sedentary lean rats. Exercise treatment resulted in greater decrements in body wt in obese than in lean rats, but did not result in absolute weight loss in either group. At 12 weeks of age, fat pad weights in principle depots were 10-15 times greater in corpulent than in lean rats and were significantly smaller in the exercised groups of both phenotypes, and corresponded with lower relative adiposity compared to corresponding sedentary groups. Heart weights were greater in corpulent than lean, while gastrocnemius muscle weights were similar in both phenotypes. Exercise was without effect on the weight of either muscle tissue in either phenotype. Interscapular brown adipose tissue weights and the IBAT:BW ratio were greater in obese than in lean rats. IBAT weights were lower in exercised than sedentary rats of either phenotype, but the IBAT:BW ratio was lower only in the obese exercised rats. In sedentary rats, L-alpha-glycerophosphate dehydrogenase and malic enzyme activity were greater in obese than lean, and exercise treatment resulted in increased L-alpha-glycerophosphate dehydrogenase and malic enzyme only in lean rats. These results are consistent with a redistribution of energy expenditure from energy storing to energy dissipating pathways following vigorous exercise, resulting in slowed rates of weight gain and body fat accretion in both lean and obese animals, with the most significant decrements among pre-obese rats.     

Hormonal and lipogenic and gluconeogenic enzymatic responses in LA/N-corpulent rats

Genetically obese normotensive rats, LA/N-corpulent (cp), were fed ad libitum diets containing either 54% sucrose or cooked corn starch for 12 weeks. Twenty-four rats were used for the study; half were corpulent (cp/cp) and half were lean (cp/+ or +/+). Fasting levels of plasma insulin, glucose, corticosterone, glucagon and growth hormone, and activities of liver and epididymal fat pad glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), and liver and kidney glucose-6-phosphatase (G6Pase), fructose 1,6-diphosphatase (FDPase), and phosphoenolpyruvate carboxykinase (PEPCK) were measured. A significant phenotype effect was observed in insulin, corticosterone, growth hormone, and liver G6PD, ME, FDPase, and kidney PEPCK, G6Pase, FDPase, and epididymal fat pad G6PD and ME (corpulent greater than lean), and glucagon (lean greater than corpulent). Diet effect (sucrose greater than starch) was significant for plasma glucose, liver ME, and kidney G6Pase. Although not significant at the P less than 0.05 level, insulin, corticosterone, liver G6PD and FDPase and kidney FDPase tended to be higher in sucrose-fed rats. This study suggests that the corpulent rat is more lipogenic and gluconeogenic than the lean, and that the hormones responsible are effective in keeping both the lipogenic and gluconeogenic enzyme activity elevated.     

Prevention of myocardial disease in JCR:LA-corpulent rats by running

The JCR:LA-corpulent rat is a congenic strain that, if homozygous for the cp gene, is obese with a very low-density lipoprotein hyperlipidemia and is insulin resistant. The male corpulent rats develop atherosclerotic lesions of the major arteries and myocardial lesions. Corpulent and lean male rats were induced through mild food restriction to run intensively (approximately 6,000 m/day) from 6 wk to 6 mo of age. Food restriction, especially when coupled with running, lowered all classes of lipids in the whole serum of corpulent rats. The principal changes in lipid concentrations were in the very low-density lipoprotein fraction. Food restriction caused a significant drop in fasting insulin levels of corpulent rats and decreased beta-cell hyperplasia. Both effects were more marked in the running animals. There was a significant decrease in myocardial lesion frequency in the food-restricted corpulent rats and an absence of lesions in the running rats. The results indicate that intensive physical activity can largely correct the lipid abnormalities and insulin resistance of this atherosclerosis-prone strain, and these changes are associated with inhibition of the disease process. However, moderate food restriction has similar effects, and the greater effects seen with intensive running may simply reflect an effectively more severe metabolic restriction in the presence of the exercise.     

Hypersecretion of VLDL, but not HDL, by hepatocytes from the JCR:LA-corpulent rat

The JCR:LA-corpulent male rat, when homozygous for the cp gene (cp/cp) is hyperlipidemic and prone to atherosclerosis. Both male and female cp/cp rats have markedly elevated serum levels of triacylglycerols and phospholipids [Dolphin, P.J. et al. 1987. Biochim. Biophys. Acta. 919: 140-148]. In the present study, monolayer cultures of hepatocytes were prepared from male and female, corpulent and lean, rats. There was a marked hypersecretion of all very low density lipoprotein (VLDL) lipid and apoprotein components from corpulent-derived cells. The increased secretion most likely accounts for the increased levels of VLDL lipids and apoproteins previously observed in serum. In contrast, there was no difference between the corpulent and lean hepatocytes in their secretion of high density lipoprotein (HDL) lipids and apoproteins. The difference in triacylglycerol secretion between the lean and corpulent cells was sustained even when the cells were cultured for 24, 48, and 72 h prior to the experiment, by which time the hormonal differences between the corpulent and lean animals would have been largely eliminated. The magnitude of the difference in triacyglycerol secretion did not diminish with increasing time in culture. The biochemical basis responsible for the hypersecretion of VLDL has not yet been established. However, preliminary results suggest that there is an inherent difference in glycerolipid metabolism in the two types of hepatocytes.     

Comparative hormonal profile of two newly developed obese congenic rat strains

1. The effect of feeding diets containing either 54% sucrose or cooked corn starch for 12 weeks on levels of fasting plasma insulin, corticosterone, growth hormone and glucagon were compared in two newly developed genetically obese rat strains--the normoglycemic LA/N-cp and the diabetic SHR/N-cp. 2. In corpulent rats of either strain, levels of plasma insulin and corticosterone were greater when compared to the lean littermates. Corpulent LA/N-cp rats had lower levels of plasma glucagon and higher levels of plasma growth hormone than did lean LA/N-cp rats. 3. SHR/N-cp rats fed sucrose had greater levels of corticosterone and glucagon than did SHR/N-cp rats fed starch.     

Nuclear cholesterol content and nucleoside triphosphatase activity are altered in the JCR:LA-cp corpulent rat

A nuclear pore complex-associated nucleoside triphosphatase (NTPase) activity is believed to provide energy for nuclear export of poly(A)+ mRNA. This study was initiated to determine if nuclear membrane lipid composition is altered during chronic hyperlipidemia, and what effect this has on NTPase activity. The JCR:LA-cp corpulent rat model is characterized by severe hypertriglyceridemia and moderate hypercholesterolemia, and thus represents an ideal animal model in which to study nuclear cholesterol and NTPase activity. NTPase activity was markedly increased in purified hepatic nuclei from corpulent female JCR:LA-cp rats in comparison to lean control rats as a function of assay time, [GTP], [ATP], and [Mg²⁺]. Nuclear membrane cholesterol and phospholipid content were significantly elevated in the corpulent animals. Nuclei of corpulent animals were less resistant to salt-induced lysis than nuclei of lean animals, suggesting a change in relative membrane integrity. Together, these results indicate that altered lipid metabolism in a genetic corpulent animal model can lead to changes in nuclear membrane lipid composition, which in turn may alter nuclear membrane NTPase activity and integrity. © 1996 Wiley-Liss, Inc.     

Triiodothyronine (T3) neogenesis in lean and obese LA/N-cp rats

Pre-obese LA/N-cp rats consumed more food and gained weight more rapidly than their lean littermates, and measures of adipose tissue depots indicated that the excess weight was deposited principally as carcass fat. Serum T3 concentrations and resting metabolic rates were lower in corpulent than in lean animals, consistent with a greater efficiency of weight gain in those animals. In vitro measures of T3 neogenesis from T4 were lower in corpulent than in lean animals in liver, kidney, and skeletal muscle and greater in interscapular brown adipose tissue. The intracellular generation of T3 from T4 is a fundamental component of the normal adaptive response to alterations in diet and environment, and is an essential prerequisite for the expression of non-shivering thermogenesis. These results are consistent with a functional impairment in the activity of the enzyme T4-5'-deiodinase in peripheral tissues, and suggest that this impairment is contributory if not causative of obesity in this strain of rat.     

The effects of the intestinal glucosidase inhibitor acarbose on cholesterogenesis in corpulent rats.

1. Groups of lean and obese LA/N-cp and obese Type II diabetic SHR/N-cp rats were fed semisynthetic diets with or without the alpha-glucosidase inhibitor acarbose (ACB, 100 mg/kg diet, p.o.) from 8 until 15 weeks of age, and measures of fasting serum total cholesterol (TC), insulin (INS), and hepatic HMG-CoA synthase activity determined at the end of the study. 2. ACB was without marked effect on mean food intake in either strain or either phenotype, and resulted in less weight gain and decreased adipose mass in obese LA/N-cp rats. INS was greater in the obese than the lean phenotype of both strains, and ACB resulted in greater reductions in INS in obese LA/N-cp than in obese LA/N-cp rats. 3. Serum TC concentrations were greater in the obese than in the lean phenotype of both strains, and ACB resulted in decreases in TC in both strains and in lower beta:alpha lipoprotein cholesterol ratios in obese LA/N-cp rats. Liver HMG Co-A synthase activity was greater in lean than obese rats and ACB resulted in normalization of enzyme activity in obese LA/N-cp but not SHR/N-cp rats. 4. These results confirm the hypercholesterolemia which occurs in the obese phenotype of the corpulent rat strains, and indicates that ACB may bring about significant reductions in body weight and fatness, TC, and in improved beta:alpha lipoprotein ratios and HMG-CoA synthase activity in obesity.(ABSTRACT TRUNCATED AT 250 WORDS)     

High glucose concentrations induce oxidative damage to mitochondrial DNA in explanted vascular smooth muscle cells

Oxidative stress is considered to be one of the mechanisms leading to atherosclerosis. It occurs in response to injury or to altered metabolic state. Alterations in cell growth (proliferation or apoptosis) can also contribute to the pathogenesis of atherosclerosis and is influenced by oxidative stress. Smooth muscle cells (SMC) from aortic explants of JCR:LA-cp homozygous cp/cp corpulent rats who are genetically predisposed to develop atherosclerosis exhibit increased SMC proliferation, which can be attenuated by exercise and food restriction. This study was conducted to characterize the effects fo oxidative stress and high glucose media on cell growth and its relationship to mitochondrial DNA integrity and gene expression in explanted aortic SMC from corpulent and lean JCR:LA-cp rats. The results show that SMC from the cp/cp rat appear to be resistant to oxidant-induced cell death and that they accumulate mitochondrial DNA mutations, probably as a result of a reduction in apoptosis. These data suggest that susceptibility to age- and glucose-related atherosclerosis may be related to alterations in redox signaling.     

Hypothalamic neuropeptide Y disturbances in the obese (cp/cp) JCR:LA corpulent rat.

Regional hypothalamic neuropeptide Y (NPY) concentrations were compared between cp/cp JCR:LA corpulent rats, which were grossly obese, hyperphagic, and hyperinsulinemic, and lean (+/+) controls. In freely fed cp/cp rats, NPY levels in the arcuate nucleus (ARC) were 31% higher than in lean rats (p less than 0.001). In lean rats, chronic food restriction significantly raised NPY levels by 22% in the ARC (p less than 0.05) and by 44% in the dorsomedial nucleus (DMH; p less than 0.05). By contrast, food-restricted cp/cp rats showed no change in the ARC, but NPY levels rose in the DMH (by 36%; p less than 0.05) and ventromedial nucleus (31%; p less than 0.05). Increased NPY levels in the ARC, the major site of hypothalamic NPY synthesis, suggests increased NPYergic activity in cp/cp rats; given the central actions of NPY, this could contribute to hyperphagia, obesity, and hyperinsulinemia in this syndrome. Abnormal NPY responses to food deprivation further suggest dysregulation of NPY in cp/cp rats.     

Serum lipids and lipoproteins in the atherosclerosis prone LA/N corpulent rat

The LA/N rat is one of two congenic strains bred from the original obese, hyperphagic and hypertensive rats of Koletsky. With the exception of hypertension the LA/N strain, when homozygous for the corpulent gene, is phenotypically similar to the parent Koletsky strain and prone to the development of vascular and myocardial lesions. Here we report a detailed analysis of the serum lipids, lipoproteins and apolipoproteins B, E and A-I levels in young adult homozygous corpulent (cp/cp) rats of both sexes and in lean males of the same age which were demonstrable non-carriers (+/+) of the cp gene. Both male and female cp/cp rats were hypertriglyceridemic (282-512 mg/100 ml) and moderately hypercholesterolemic (74-84 mg/100 ml). Elevations in these lipids reflected the presence of large (622 A), triacylglycerol-rich and apoprotein-poor VLDL containing both apolipoproteins Bh and B1 and increased phospholipid-rich HDL. Similar, but less pronounced, elevations in serum apolipoproteins B and E in the cp/cp rats when compared to the +/+ animals were also noted. Apolipoproteins A-I levels were 2.7-3-fold higher in cp/cp rats. The levels of VLDL were significantly higher in female cp/cp rats; however, the levels of IDL (intermediate-density lipoproteins), LDL and HDL were significantly lower than in the more atherosclerosis prone male cp/cp rats. Similarly, apolipoprotein A-I was higher and apolipoprotein B lower in the male cp/cp than in the female cp/cp rats. The LDL (d = 1.030-1.063 g/ml) in cp/cp rats, like that in normal animals, was heterogeneous and contained apolipoproteins Bh, E, A-I and C. This fraction was significantly elevated in male cp/cp rats when compared to females but still represented less than 13% of the total serum cholesterol and less than 6% of the total serum lipids in 3-month-old cp/cp animals. The ratio of cholesterol to phospholipids was significantly lower for all lipoproteins in cp/cp rats when compared to +/+ males and these ratios for female cp/cp rats were in all cases lower than those of male cp/cp animals.