A polymorphism of the interferon-gamma-inducible protein 30 gene is associated with hyperglycemia in severely obese individuals.

A previous expression profiling of visceral adipose tissue (VAT) revealed that the immune response gene interferon-gamma-inducible protein 30 (IFI30) gene was 1.72-fold more highly expressed in non-diabetic severely obese men with the metabolic syndrome as compared to those without. Given the importance of low-grade inflammation in obesity-related metabolic complications, we hypothesized that variants in the IFI30 gene are associated with cardiovascular disease (CVD) risk factors. A detailed genetic investigation was performed at the IFI30 locus by sequencing its promoter, exons and intron-exon junction boundaries using DNA of 25 severely obese men. Among the 21 sequence-derived single-nucleotide polymorphisms (SNPs), 5 tagged SNPs (covering 100% of the common SNPs identified) were genotyped in two independent samples of severely obese patients (total n = 1,283). Using a multistage experimental design, chi-square analyses and logistic regressions were performed to compare genotype frequencies and compute odds-ratios (OR) for low and high CVD risk groups (dyslipidemia, hyperglycemia/diabetes and hypertension). A significant association was observed with the non-synonymous SNP rs11554159 (p.R76Q), where GA individuals showed lower risk (OR = 0.67; P = 0.0009) for hyperglycemia/diabetes as compared to homozygotes for the major allele (GG). No association was observed between rs11554159 and VAT IFI30 mRNA levels (P = 0.81), and the expression levels were not correlated with fasting plasma glucose levels (P = 0.31) in 112 non-diabetic severely obese women. The localization of rs11554159 near the active site of IFI30 suggests a functional effect of this SNP. This study showed a novel association between rs11554159 (p.R76Q) polymorphism at the IFI30 locus and the risk of hyperglycemia/diabetes in severely obese individuals.

Additive action of 11beta-HSD1 inhibition and PPAR-gamma agonism on hepatic steatosis and triglyceridemia in diet-induced obese rats.

Both 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) inhibition and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonism reduce liver and plasma lipids in rodents through partly distinct mechanisms. This study aimed to assess their additivity of action on liver and plasma lipids in a model of diet-induced steatosis. Rats were fed an obesogenic diet and were treated either with an 11beta-HSD1 inhibitor (Compound A, 3 mg kg(-1) day(-1)) or rosiglitazone (RSG, 5 mg kg(-1) day(-1)) or both for 6 weeks. Compound A and RSG reduced liver steatosis and triglyceridemia, and did so additively when given in combination. The 11beta-HSD1 inhibitor had no effect on serum adiponectin, but increased liver adiponectin receptor type 2 (Adipo-R2) mRNA levels. Conversely, RSG increased serum adiponectin, a likely mediator of its antisteatotic action, but had no effect per se on the Adipo-R2 expression. mRNA levels of representative genes of fatty acid oxidation tended to be increased by both compounds. The study shows that combined 11beta-HSD1 inhibition and PPAR-gamma agonism additively reduce liver steatosis and triglyceridemia, which may eventually prove therapeutically useful.

Kinetics of plasma apolipoprotein C-III as a determinant of diet-induced changes in plasma triglyceride levels.

OBJECTIVE: To compare the effect of a high monounsaturated fatty acid (MUFA) diet and of a control low-fat diet consumed under ad libitum conditions on plasma apolipoprotein (apo) C-III metabolism. DESIGN: Randomized, two-arm parallel dietary trial. SETTING: Diets were prepared and consumed at the metabolic kitchen of the Department of Food Sciences and Nutrition, and laboratory analyses were performed at the Institute of Nutraceuticals and Functional Foods at Laval University. SUBJECTS AND INTERVENTIONS: Eighteen men were randomly assigned to either the high MUFA diet or the low-fat control diet, which they consumed for 6-7 weeks. Before and after the dietary intervention, subjects received a primed-constant infusion of [5,5,5-D(3)]-L-leucine for 12 h under constant feeding conditions for the determination of plasma apoC-III kinetics. RESULTS: The high-MUFA diet and the low-fat control diet had no significant impact on plasma apoC-III production rate (PR) or fractional catabolic rate. However, diet-induced variations in plasma apoCIII PR predicted the reduction in plasma triglycerides and apoC-III levels (r=0.85, P<0.01 and r=0.73, P<0.05, respectively) in the high MUFA group only. CONCLUSIONS: These results suggest that the hypotriglyceridemic effect of a high-MUFA diet may be attributable in part to a reduced hepatic production of apoC-III. SPONSORSHIP: This study was supported in part by an operating grant from the Canadian Institutes of Health Research (CIHR), and the Canada Research Chair in Nutrition and Cardiovascular Health (B Lamarche).

A GWAS follow-up of obesity-related SNPs in SYPL2 reveals sex-specific association with hip circumference.

OBJECTIVE: A novel single-nucleotide polymorphism (SNP) associated with morbid obesity was recently identified by exome sequencing. The purpose of this study was to follow up this low-frequency coding SNP located within the SYPL2 locus and associated with body mass index in order to reveal novel associations with obesity-related traits. METHODS: The body mass index-associated SNP (rs62623713 A>G [chr1:109476817/hg19]) and two tagging SNPs within the SYPL2 locus, rs9661614 T>C (chr1:109479215) and rs485660 G>A (chr1:109480810), were genotyped in the obesity (n = 3,017) and the infogene (n = 676) cohorts, which were further combined, leading to a larger cohort of 3,693 individuals. Association testing was performed by general linear models in the obesity cohort and validated by joint analysis in the combined cohort. RESULTS: rs9661614 and rs485660 were significantly associated with hip circumference (HC) in the obesity cohort, with heterozygotes exhibiting a significantly lower HC. These results were validated by joint analysis for rs9661614 (false discovery rate [FDR]-corrected P = 7.5 × 10-4) and, to a lesser extent, for rs485660 (FDR corrected P = 3.9 × 10-2). The association with HC remained significant for rs9661614 when tested independently in women (FDR-corrected P = 1.7 × 10-2), but not for rs485660 (FDR-corrected P = 0.2). Both associations were absent in men. CONCLUSIONS: This study reveals strong evidence for a novel association between rs9661614 (T>C) and HC in women, which likely reflects a preferential association of SYPL2 to a gynoid profile of fat distribution. The study findings support a clinical significance of SYPL2 worth considering when assessing risk factors associated with obesity.

Peroxisome proliferator-activated receptor γ activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes.

AIM: Peroxisome proliferator-activated receptor (PPAR) γ activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPARγ agonism acts upon the multi-level modulation of depot-specific lipid storage remains incompletely understood. METHODS: We evaluated herein triglyceride-derived lipid incorporation into adipose tissue depots, LPL mass and activity, mRNA levels and content of proteins involved in the modulation of LPL activity and fatty acid transport, and the expression/activity of enzymes defining adipose tissue lipogenic potential in rats treated with the PPARγ ligand rosiglitazone (30 mg kg(-1)  day(-1) , 23 days) after either a 10-h fasting period or a 17-h fast followed by 6 h of ad libitum refeeding. RESULTS: Rosiglitazone stimulated lipid accretion in subcutaneous fat (SF) ~twofold and significantly reduced that of visceral fat (VF) to nearly half. PPARγ activation selectively increased LPL mass, activity and the expression of its chaperone LMF1 in SF. In VF, rosiglitazone had no effect on LPL activity and downregulated the mRNA levels of the transendothelial transporter GPIHBP1. Overexpression of lipid uptake and fatty acid transport proteins (FAT/CD36, FATP1 and FABP4) and stimulation of lipogenic enzyme activities (GPAT, AGPAT and DGAT) upon rosiglitazone treatment were of higher magnitude in SF. CONCLUSIONS: Together these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPARγ activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.

Response of adipose tissue lipoprotein lipase to the cephalic phase of insulin secretion.

Modulation of lipoprotein lipase (LPL) allows a tissue-specific partitioning of triglyceride-derived fatty acids, and insulin is a major modulator of its activity. The present studies were aimed to assess in rats the contribution of insulin to the response of adipose tissue and muscle LPL to food intake. Epididymal and retroperitoneal adipose LPL rose 65% above fasting values as early as 1 h after the onset of a 30-min high-carbohydrate meal, with a second activity peak 1 h later that was maintained for an additional 2 h. Soleus muscle LPL was decreased by 25% between 0.5 and 4 h after meal intake. The essential contribution of insulin to the LPL response to food intake was determined by preventing the full insulin response to meal intake by administration of diazoxide (150 mg/kg body wt, in the meal). The usual postprandial changes in adipose and muscle LPL did not occur in the absence of an increase in insulinemia. However, the early (60 min) increase in adipose tissue LPL was not prevented by the drug, likely because of the maintenance of the early centrally mediated phase of insulin secretion. In a subsequent study, rats chronically implanted with a gastric cannula were used to demonstrate that the postprandial rise in adipose LPL is independent of nutrient absorption and can be elicited by the cephalic (preabsorptive) phase of insulin secretion. Obese Zucker rats were used because of their strong cephalic insulin response. After an 8-h fast, rats were fed a liquid diet ad libitum (orally, cannula closed), sham fed (orally, cannula opened), or fed directly into the stomach via the cannula during 4 h. Insulinemia increased 10-fold over fasting levels in ad libitum- and intragastric-fed rats and threefold in sham-fed rats. Changes in adipose tissue LPL were proportional to the elevation in plasma insulin levels, demonstrating that the cephalic-mediated rise in insulinemia, in the absence of nutrient absorption, stimulates adipose LPL. These results demonstrate the central role of insulin in the postprandial response of tissue LPL, and they show that cephalically mediated insulin secretion is able to stimulate adipose LPL.

Plasma lipoprotein profile and lipolytic activities in response to the substitution of lean white fish for other animal protein sources in premenopausal women.

A crossover study was conducted to examine the effects on plasma lipoprotein concentrations of substituting lean white fish (LWF) for beef, port, veal, eggs, and milk products (BPVEM) within prudent isoenergetic diets. Fourteen premenopausal women received 8784 kJ--20% as protein, 50% as carbohydrates, and 30% as lipids [ratio of polyunsaturated to monounsaturated to saturated fatty acids (P:M:S) of 1:1:1 compared with 0.4:1:1 in preexperimental diet]--and 260 mg cholesterol/d. After 4 wk, the BPVEM diet significantly reduced concentrations of plasma cholesterol, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol, apolipoprotein B, HDL-apolipoprotein A-I, and LDL-apolipoprotein B (P<0.05) as well as plasma postheparin hepatic triacylglycerol lipase activity compared with the preexperimental diet. These effects are probably attributable to elevation of the P:M:S. These responses were not observed with the LWF diet, suggesting that fish protein in LWF maintains unchanged plasma cholesterol concentrations despite a high P:M:S. The LWF diet, compared with the preexperimental diet, reduced very-low-density-lipoprotein triacylglycerol (P<0.05) and also the ratio of LDL cholesterol to apolipoprotein B (P<0.05), revealing the presence of denser LDL particles. Compared with the BPVEM diet, the LWF diet induced lower concentrations of very-low-density-lipoprotein triacylglycerols (P<0.05) and higher concentrations of LDL triacylglycerol and LDL apolipoprotein B (P<0.05), which were not associated with any increase in lipoprotein lipase activity. These results suggest that LWF as a substitute for BPVEM in isoenergetic diets with an elevated P:S produces minimal improvement in the lipoprotein profile in premenopausal women.

Relationship between dietary proteins, their in vitro digestion products, and serum cholesterol in rats.

A relationship was assessed between the amino acid composition of 9 protein sources or of their in vitro digestion products and total serum cholesterol in rats. Three animal proteins (casein, beef, fish) and 6 vegetable proteins (soy, pea, peanut meal, rapeseed, oatmeal, wheat gluten) were tested. The intact protein sources were submitted to an enzymatic proteolysis according to a new in vitro digestion method. Each protein source was hydrolyzed for 30 min with pepsin at pH 1.9, then with 10 mg pancreatin at basic pH in a dialysis cell. The digestion products diffused through the dialysis membrane of the cell and were collected by a circulating sodium phosphate buffer over a 6-h period. They were likely to correspond to end products luminal in vivo digestion. The aromatic and the basic amino acids were present in higher proportions in the digestion products than in the intact protein sources, reflecting the specificity of the proteolytic enzymes. Total serum cholesterol was measured on male Sprague-Dawley rats fed cholesterol-free or cholesterol-enriched (1% cholesterol, 0.5% cholic acid) semipurified diets containing protein sources. Total serum cholesterol ranged from 70 mg/dl with the pea diet to 98 mg/dl with the peanut meal diet in rats fed cholesterol-free diets and from 163 mg/dl with the wheat gluten diet to 313 mg/dl with the casein diet in rats fed the cholesterol-enriched diets. These results suggested no specific effect of protein from animal or vegetable origin on total serum cholesterol in rats. In rats fed cholesterol-enriched diets, significant correlations were observed between total serum cholesterol and tyrosine content or leucine/isoleucine ratio of digestion products. These correlations were stronger than those observed with intact protein sources.

Determination of changes in specific gene expression by reverse transcription PCR using interspecies mRNAs as internal standards.

A method is described for the determination of changes in gene expression by reverse transcription of the target mRNA followed by PCR amplification of the resulting cDNA (RT-PCR), using the lipoprotein lipase gene as the model system. Known proportions of human and rat adipose tissue homogenates are mixed and are processed together throughout the RT-PCR procedure so that the rat tissue serves as an internal standard for the measurement of human adipose tissue lipoprotein lipase (LPL) in all steps including RNA extraction, reverse transcription and PCR amplification. Taking advantage of the highly conserved sequence of the LPL gene across species, selected homologous regions of the human and rat genes are amplified using the same primer pair and resulting in the same lengths of amplified DNA fragments. The two amplified products are then separated from each other by making use of differences in the position of a restriction site in the two amplified DNA fragments. The method is simple, precise and reproducible and avoids construction of tailored nucleic acids for use as internal standards.

Contribution of hyperinsulinemia to modulation of lipoprotein lipase activity in the obese Zucker rat.

This study was designed to assess the contribution of hyperinsulinemia to the maintenance of high adipose and low muscle lipoprotein lipase (LPL) activity in the obese Zucker fa/fa rat. Insulinemia in obese Zucker rats was reduced for 4 days with a single injection of low-dose streptozotocin (STZ). Saline-injected intact obese (obese-INT) and STZ-injected obese (obese-STZ) rats were compared with a lean Fa/? reference group. LPL activity was assessed after a 12-hour fast, with or without a 1-hour refeeding period. Fasting serum insulin levels were 17-fold higher in obese-INT versus lean rats and were reduced to 60% of obese-INT levels in obese-STZ animals. In the postprandial state, serum insulin levels remained low in obese-STZ rats and were similar to the values in lean animals, whereas insulinemia increased in the obese-INT group to 18-fold the levels in lean rats. Serum glucose, nonesterified fatty acid (NEFA), and triglyceride levels, which were higher in obese-INT versus lean rats, were further increased in the obese-STZ group. Tissue weights of obese rats were unaffected by STZ treatment. Fasting LPL specific activity was higher in white adipose tissue ([WAT] +87%) and brown adipose tissue ([BAT] +167%) of obese-INT versus lean rats. Reducing the insulinemia in obese-STZ rats reduced fasting enzyme activity to the levels in lean animals in both WAT and BAT. Insulinemia and adipose LPL activity were positively correlated in the fasted state. Acute food intake increased WAT LPL activity in lean animals, but not in obese animals. Soleus LPL activity was lower in obese-INT compared with lean rats and was further decreased in obese-STZ animals. Heart LPL was decreased only in obese-STZ rats compared with the lean group. LPL in muscle tissue was not correlated with insulinemia, but an inverse relationship was found between serum NEFA levels and enzyme activity. It is concluded that in the obese Zucker rat, hyperinsulinemia is responsible for the maintenance of elevated basal LPL activity in adipose tissue independently of fat mass, whereas muscle enzyme activity appears to be more strongly and inversely related to the availability or tissue utilization of lipid substrates.

Involvement of insulinemia in the postprandial hypotriacylglycerolemia induced by prazosin in the rat.

The purpose of the present study was to evaluate the role of insulin as a possible mediator of the hypotriacylglycerolemic effect of alpha 1-adrenergic blockade. To this end, determinants of triacylglycerol (TG) metabolism were measured in animals having normal postprandial fluctuations in insulin levels (intact rats) and in others having invariable insulin concentrations (insulin-depleted rats infused long-term with insulin-delivering minipumps). Postprandial changes in plasma TG level, TG secretion rate (TGSR), TG elimination rate (TGER), and lipoprotein lipase (LPL) activity of white (WAT) and brown (BAT) adipose tissues, vastus lateralis muscle (VLM), and heart were measured in animals acutely injected or not with the alpha 1-antagonist prazosin 1 hour before the intake of a high-sucrose, fat-free meal. In intact rats, postprandial increases in glucose and insulin levels were potentiated by administration of prazosin before meal intake. The postmeal increase of plasma TG level was abolished by prazosin in intact animals, whereas this effect was absent in animals with invariable insulin levels. Intact animals treated with prazosin displayed both a lower TGSR (P < .01) and a higher TGER (P < .01) than their saline-injected counterparts. In animals with invariable insulin, both TGSR and TGER remained unaffected by prazosin treatment. Prazosin treatment of intact animals did not affect LPL activity in WAT, but increased enzyme activity in BAT (P < .02). In insulin-infused animals, prazosin increased LPL activity in WAT (P < .02) and BAT (P < .03). alpha 1-Adrenergic blockade had no effect on LPL in VLM and heart. These results confirm that alpha 1-adrenergic blockade prevents the postprandial increase in plasma TG level that follows the ingestion of a high-sucrose meal both by decreasing TGSR and by increasing TGER. The findings also demonstrate that these effects of prazosin are indirect and that their occurrence requires the postprandial increase in circulating insulin levels.

Dietary rat models in which the development of hypertriglyceridemia and that of insulin resistance are dissociated.

The consequences of chronic ingestion of a high-carbohydrate (starch + glucose [HCHO]) and high-fat (lard + corn oil [HFAT]) diet on triglyceride metabolism and insulin sensitivity were evaluated in fasted and fed rats. Compared with their HFAT counterparts, animals fed the HCHO diet displayed fasting and postprandial hypertriglyceridemia that was apparent after 3 weeks of feeding and persisted after 6 weeks. It was determined that hypertriglyceridemia was due to oversecretion of triglycerides into the circulation. During fasting triglyceride accumulation in plasma after administration of Triton WR1339 was indeed twofold higher in HCHO than in HFAT rats, whereas the global capacity for intravascular triglyceride hydrolysis, as assessed by an intravenous fat tolerance test and measurement of postheparin plasma lipoprotein and hepatic lipase activities, was comparable in both dietary cohorts. The postprandial increase in triglycerides after a high-carbohydrate meal was larger in HCHO than in HFAT rats. A fasting intravenous glucose tolerance test (IVGTT) showed that HFAT animals displayed insulin resistance after 3 weeks of feeding, which worsened after 6 weeks of treatment. Thus, the HCHO diet elicited fasting and postprandial hypertriglyceridemia without impairment of insulin sensitivity as compared with the HFAT diet, whereas the latter brought about deterioration of the sensitivity of glucose metabolism to insulin without affecting triglyceridemia. From these studies and other animal models, it is suggested that rapid delivery of fatty acids to tissues from chylomicron-derived triglycerides leads to insulin insensitivity, while fatty acids may not be available to increase endogenous production of triglycerides because they are mainly oxidized. In contrast, dietary starch/glucose increases hepatic synthesis and secretion of triglycerides that result in hypertriglyceridemia, but the deleterious effects of glucose-fatty acid competition on insulin sensitivity are prevented because endogenously derived triglycerides are catabolized more slowly and glucose is available for oxidation. The present results support the concept that coexistence of hypertriglyceridemia and resistance of glucose metabolism to insulin may be frequent but not obligatory.

Influence of a palatable, high-fat diet, and exercise training on the high-density lipoprotein to total cholesterol ratio in the rat.

The influence of a palatable, high-energy diet, and exercise training on the levels of serum total cholesterol (CHOL) and CHOL carried by high-density lipoproteins (HDL CHOL) was investigated. Female rats were fed either a laboratory chow or a diet made of palatable food items containing a high level of fat. The animals receiving the latter were divided into groups fed either ad libitum, or pair-fed, on a calorie basis, with the chow-fed animals. Half of the animals were submitted to a swimming program for 4 wk. Body weight, total and HDL CHOL were measured at the end of the treatments. Exercise-trained rats ingested the same amount of calories as their sedentary counterparts, while the animals fed with high-energy diet ate almost twice as many calories as the chow-fed groups. The sedentary animals fed the palatable diet had higher body weights than the chow-fed animals, and exercise prevented this weight increase. Exercise did not have any significant effect on serum total CHOL, but increased significantly the HDL/total CHOL ratio by 15% in the chow-fed animals. The palatable diet increased total CHOL, and decreased the HDL/total CHOL ratio in sedentary animals, whereas the ratio in their trained counterparts was comparable to that of the sedentary chow-fed group. Exercise can thus prevent both weight gain and a decrease in HDL/total CHOL ratio produced by a palatable, high-energy diet in the female rat.

Chronic effects of dehydroepiandrosterone on rat adipose tissue metabolism.

The goal of the present study was to examine cellular mechanisms that regulate adipose cell metabolism in ovariectomized (OVX) and intact rats that were subjected to long-term (27 weeks) treatment with dehydroepiandrosterone (DHEA). Forty-eight 16-month-old female rats were divided into 4 groups of 9 to 11 animals (intact, intact-DHEA, OVX, OVX-DHEA). Adipose tissue lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), and cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (cAMP-PDE) activities were determined, and alpha2-, beta1/beta2-, and beta3-adrenoceptors (ARs) were quantified. DHEA did not affect body weight, fat, or muscle mass in intact rats. The similar retroperitoneal fat pad weight of intact-DHEA rats compared to intact animals was in agreement with the lack of difference in the enzyme activities and AR densities. The increased body weight of OVX rat was paralleled by a greater retroperitoneal adipose tissue mass (P <.01), which was in turn associated with a marked rise in LPL activity (P <.005) and a slight decrease in HSL activity (P <.05) compared to intact animals. OVX-DHEA rats, compared to untreated OVX animals, had a smaller retroperitoneal fat depot, which correlated with a decrease in LPL activity (P <.005) and moderate increase in both HSL activity and beta3-AR density (P <.05). DHEA-treatment lowered fasting insulin and triglyceride levels in both intact and OVX rats (P <.05). Plasma testosterone, androsterone, androstenedione, and androstenediol levels were also significantly increased in both intact-DHEA and OVX-DHEA rats compared to untreated animals (P <.0001). These findings suggest that the antiobesity action of DHEA may be related in part to changes in lipase activities and in beta3-AR density, and that it is dependent on the ovarian status of the animal.

Lipoprotein lipase in adipose tissues of rats running during cold exposure.

This study evaluated the individual and combined effects of exercise training and intermittent cold exposure of similar energy cost on serum lipids and lipoprotein lipase (LPL) activity on epididymal white (WAT) and interscapular brown (BAT) adipose tissues of the rat. The animals were subjected daily to 2 h of treadmill running at 24 degrees C or for the same period of time at -5 degrees C, with or without exercise, for 28 days. Exercise training lowered serum triglycerides (P less than 0.01), whereas serum cholesterol was reduced by cold exposure (P less than 0.05). Cholesterol lowering occurred in the lipoproteins of lower densities. WAT weight was diminished by both treatments. Exercise training had an overall lowering effect on WAT total LPL activity (P less than 0.05), whereas cold exposure did not affect enzyme activity significantly. Exercise and intermittent cold interacted on BAT weight. Cold increased total BAT LPL activity (P less than 0.03), whereas simultaneous exercise in the cold greatly diminished this effect. Serum insulin levels were not affected by either treatment. Thus, in WAT, intermittent exposure to cold did not have any lasting effect on LPL activity, whereas exercise training decreased the latter. In contrast, exercise did not influence LPL in BAT of rats not exposed to cold but prevented the stimulation of enzyme activity induced by repeated cold exposure. These results support the notion that the regulation of LPL is tissue specific.

Serum lipids and cholesterol distribution in lipoproteins of exercise-trained female rats fed sucrose.

This study was undertaken to evaluate the combined effects of sucrose feeding and exercise training on serum insulin, triglycerides, as well as cholesterol and its distribution into lipoproteins of female Wistar rats. The animals were fed ad libitum either laboratory chow alone, or chow and a 32% aqueous sucrose solution. Half of each dietary group was submitted to an exercise-training program. Both sucrose feeding and exercise training elicited greater energy intake. Sucrose feeding produced a marked elevation in triglyceridemia that was prevented by exercise training. Insulin levels paralleled those of triglycerides. The sucrose-fed animals had higher total cholesterol levels than the animals given chow. Although exercise training did not affect total cholesterol in the chow-fed animals, it partly prevented the sucrose-induced elevation in total cholesterol. Cholesterol in the lipoproteins of lower densities was increased significantly with sucrose feeding, and exercise training totally prevented this augmentation. The amount of cholesterol carried by high-density lipoprotein (HDL) was not affected by exercise training in the chow-fed animals. In contrast, sucrose feeding increased HDL-cholesterol in sedentary animals, whereas exercise training partly prevented this increase. The HDL/total cholesterol ratio was similar in all groups. Changes in insulin concentration underline the importance of this hormone in the regulation of blood lipid levels.

Acute effects of exercise on triacylglycerol metabolism in fasted, untrained rats treated with nadolol.

The current study investigated the early response of some determinants of triacylglycerol (TG) metabolism to acute exercise in rats that were treated or not with the nonselective beta-adrenergic blocker, nadolol (25 mg.kg b.wt.-1.day-1 for 30 days). Measurements of hepatic TG secretion rate (HTGSR), postheparin plasma hepatic TG lipase (HTGL) activity, and that of lipoprotein lipase (LPL) in postheparin plasma, heart, vastus lateralis muscle (VLM), white (WAT) and brown (BAT) adipose tissues were carried out in untrained rats at rest or immediately after a 1 h run on treadmill (22 m.min-1, 0 degrees grade). All animals were in the fasted state. Exercise reduced serum TG levels (46% below resting levels) and doubled those of nonesterified fatty acids. HTGSR was enhanced (+28%) by exercise while HTGL activity was not modified. The decrease in postheparin plasma LPL activity (-24%) caused by exercise was consistent with a reduction in enzyme activity in WAT (-32%), BAT (-45%) and heart (-25%). One h of treadmill running did not influence LPL activity in VLM. beta-Adrenergic blockade did not affect any of the variables of lipid metabolism, except for a slight decrease in specific activity of LPL in the heart (-14%). This study demonstrates that absolute variations in HTGSR and in LPL activity cannot account for the acute fall in serum TG levels caused by moderate exercise, in fasted, untrained rats. In addition, these results show that the beta-adrenergic pathway is either not involved in, or not necessary for, the latter effects of exercise on TG metabolism.

Serum high-density lipoprotein cholesterol in male and female Olympic athletes.

High-density lipoprotein cholesterol (HDLC) is negatively associated with the risk of cardiovascular disease, and high levels of HDLC have been reported for physically active people. During the 1976 Olympic Games, held in Montreal, Canada, several physiological variables were measured in volunteer male and female Olympic athletes, from whom blood was collected. To compare these elite athletes with the general population and other physically active groups, HDLC was measured in serum samples that were kept at -80 degrees C and after precipitation of lipoproteins of lower densities by heparin-manganese. High-density lipoprotein cholesterol levels were significantly higher in women (65.2 +/- 2.1 N = 31) than in men (54.5 +/- 1.4, N = 64) (P less than 0.01). Olympic athletes had approximately 20% more HDLC than levels reported in the literature for the general population of North America. Levels of HDLC of the male Olympic athletes were comparable to those reported for elite world-class runners of comparable age. No correlation was found between HDLC and Quetelet index or maximum oxygen consumption. Levels of HDLC in athletes 20-24 yr of age were lower than in the other age groups studied and was positively correlated with age for athletes over 20 yr of age. Although a causal relationship between physical activity and HDLC remains to be established unequivocally, the present findings agree with several other studies that link various levels of physical activity with blood concentrations of HDLC higher than those found in sedentary populations.

Factorial experiment to determine influence of fish protein and fish oil on serum and liver lipids in rabbits.

Rabbits were fed purified diets consisting of casein (CA), fish protein (FP), and soy protein (SP) combined with MaxEpa oil (ME) or corn oil (CN) to determine the effects of dietary protein and lipid sources on serum total, lipoprotein, and hepatic lipid levels. Dietary proteins and lipids exerted significant (p < 0.05) separate effects on serum total cholesterol (TC) (p < 0.005), very-low-density lipoprotein cholesterol (VLDL-C) (p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (p < 0.001), whereas only dietary proteins significantly affected low-density lipoprotein cholesterol (LDL-C) (p < 0.001) and the LDL-C/HDL-C ratio (p < 0.05). Hence, FP induced serum TC (233 mg/dl), VLDL-C (22 mg/dl), and LDL-C (151 mg/dl) intermediary to hypercholesterolemic CA (TC, 319 mg/dl; VLDL-C, 57 mg/dl; LDL-C, 204 mg/dl) and cholesterol-lowering SP (TC, 129 mg/dl; VLDL-C 19 mg/dl; LDL-C, 84 mg/dl). The twofold rise in HDL-C on feeding FP (35 mg/dl), compared with CA (20 mg/dl) and SP (16 mg/dl), resulted in a drop in LDL-C/HDL-C to a level similar to that of SP groups. The cholesterol-lowering action of ME (188 mg/dl), in contrast to CN (266 mg/dl), was reflected mainly in VLDL (ME, 15 mg/dl; CN, 50 mg/dl) but also in HDL (ME, 16 mg/dl; CN, 31 mg/dl) fractions. Compared with CN, the significant (p < 0.05) ME-induced rise in serum and VLDL triglycerides was accompanied by a significant (p < 0.001) drop in lipoprotein lipase activity.(ABSTRACT TRUNCATED AT 250 WORDS)