Epididymal Fat Pad Weight Research Articles

Targeted disruption of the tumor necrosis factor-alpha gene: metabolic consequences in obese and nonobese mice.

To address the hypothesis that tumor necrosis factor (TNF)-alpha has a role in obesity-associated insulin resistance or the regulation of in vivo lipid metabolism, mice with targeted disruption of the TNF-alpha gene were generated and studied. The absence of TNF-alpha protein in TNF-null (-/-) mice was confirmed. Lean or obese (gold-thioglucose [GTG]-injected) homozygous (-/-) mice were compared with lean or obese age- and sex-matched wild-type (+/+) mice derived from the same line at 13, 19, and 28 weeks of age. The following parameters were significantly affected in lean -/- versus +/+ mice: Body weight was not affected until week 28 (decreased by 14%); epididymal fat pad weight also decreased (25%) at this time, as did percentage body fat (16%), while percentage body protein was increased 13%. Fed plasma insulin levels decreased 47% (28 weeks), triglyceride levels decreased (all three ages; maximum 35% at 19 weeks), and fed plasma leptin decreased 33% (28 weeks). Fasting glucose was slightly (10%) reduced, but the glucose response to an oral glucose tolerance test (OGTT) was not affected. There was a trend (NS) toward increased total adipose tissue lipoprotein lipase in -/- versus +/+ mice. GTG-treatment resulted in obese -/- and +/+ mice with equal mean body weights (42 and 58% increased weight versus lean mice). The following parameters were significantly different in obese -/- mice: fasting plasma glucose decreased 13% (28 weeks), fed plasma insulin decreased 67% (28 weeks), and insulin response to OGTT was decreased by 50%. For both groups of obese mice, glucose levels during the OGTT were substantially increased compared with those in lean mice; however, mean stimulated glucose levels were 20% lower in obese -/- versus +/+ mice. We conclude 1) that TNF-alpha functions to regulate plasma triglycerides and body adiposity and 2) that although TNF-alpha contributes to reduced insulin sensitivity in older or obese mice, the absence of TNF-alpha is not sufficient to substantially protect against insulin resistance in the GTG hyperphagic model of rodent obesity.

Involvement of prostaglandins in cachexia induced by T-cell leukemia in the rat

We have previously demonstrated that experimentally induced T-cell leukemia in the rat results in a rapid and severe cachexia. This weight loss is largely due to a reduction in food intake, but is also accompanied by inappropriately high rates of energy expenditure. Increases in resting oxygen consumption (V̇ o 2) of 25% to 35% above the levels of pair-fed animals were observed over the period of weight loss. The present study investigated the possible involvement of prostaglandins in the cachexia induced by T-cell leukemia in the rat. Acute systemic injection of the cyclo-oxygenase inhibitors (indomethacin 1 mg/kg or flurbiprofen 1 mg/kg intraperitoneally [IP]) significantly reduced (by 14% and 10%, respectively) the increase in metabolic rate and also reversed the elevated body temperature of leukemic animals. Intracerebroventricular (ICV) injection of indomethacin (0.2 mg/kg) had only modest effects on the increase in temperature or hypermetabolism of leukemic animals. Long-term daily injection of indomethacin or flurbiprofen (1 mg/kg/d IP) had no significant effect on food intake or body weight of leukemic animals, and neither treatment significantly affected disease status. Indomethacin significantly reduced the decline in epididymal fat pad weight of leukemic animals. These data indicate that prostaglandins, produced peripherally, are involved in the acute hypermetabolism associated with T-cell leukemia, but have little or no effect on the hypophagia or body weight loss of leukemic rats.

Effects of dietary protein level on growth and body composition in mice divergently selected for fat content

A study was conducted to examine the effects of dietary protein percentage and selection for divergence in fat content on growth and body composition in mice. The three lines used had been selected as follows: high epididymal fat pad weight as a percentage of body weight (HF), low epididymal fat pad weight as a percentage of body weight (LF) and a randomly selected control (RC). Mice from each line were allotted at weaning (3 wk of age) to one of four dietary protein percentages: 12, 16, 20, and 24%. Growth and efficiency of feed conversion were measured at 2-wk intervals and mice were killed and body composition was measured at 9-wk of age. Overall, HF mice grew faster were more efficient at converting feed to body weight gain, and had empty carcasses with a higher percentage of tat (P < 0.05) and a lower percentage of protein than LF mice. However, fat-free empty-body protein and ash percentages, protein gain, protein gain:protein intake, and protein gain:energy intake ratios were not different among genotypes. As dietary protein percentage increased, gain:feed ratio increased quadratically (P < 0.05) in all genotypes and was maximized m mice consuming 16% protein. Protein gain was maximized in mice consuming 16% protein. Feeding diets providing protein percentages above or below 16% depressed protein gain and protein gain:energy intake ratio. Genetic line-by-dietary-protein-level interactions were generally not significant for growth, feed efficiency and body composition traits. Key words: Mice, dietary protein, growth, body composition, fat deposition

Development of obesity following inactivation of a growth hormone transgene in mice

Mice with a temporally regulatable ovine metallothionein 1a--ovine growth hormone transgene (oMT1a-oGH) were utilized to study the effects of withdrawal of elevated circulating levels of growth hormone (GH) on growth and body composition. The transgene was activated from 21-42 days of age by provision of zinc sulfate in the drinking water. At 42 days, mice were allocated to either activated transgenic (remain on zinc sulfate) or inactivated transgenic (removal of zinc sulfate) groups, and to receive either ad libitum or restricted (80-90% of ad libitum) access to feed. Non-transgenic control mice were treated similarly. Body weights and intakes were recorded weekly. Mice were killed at 70 d and epididymal and subcutaneous fat pads, trimmed hind carcass and various organs were weighed. The main findings of this study are: (1) food-restricted mice possessing an activated oMT1a-oGH transgene fail to demonstrate increased growth, but exhibit significantly reduced levels of fat (P < 0.05) relative to all other genotype x feed level combinations; and (2) inactivation of the oMT1a-oGH transgene, following a period of elevated GH levels, leads to development of obesity as evidenced by two to three fold increases in epididymal and subcutaneous fat pad weights (P < 0.01) relative to both activated transgenic and non-transgenic control mice. These large increases in fat deposition also occurred when intake was restricted to 80-90% of ad libitum levels, indicating that metabolic changes independent of intake occur in these inactivated transgenic mice. It is possible that highly elevated production of GH in activated oMT1a-oGH transgenic mice leads to (1) enhanced promotion of preadipocyte differentiation, leading to increased numbers of adipocytes that, upon cessation of oGH production, are available for lipid deposition resulting in obesity, or (2) alterations in production of or responsiveness to insulin, leading to increased fat deposition upon removal of the chronic anti-lipogenic actions of GH. The oMT1a-oGH transgenic mouse line should provide a new genetic model with which to investigate the mechanisms by which growth hormone affects obesity.

Weight cycling-induced reduction of linoleic acid in carcass and adipose tissue in rats

Recent epidemiological studies have proposed the hypothesis that large fluctuations in body weight over time may increase the risk of cardiovascular disease. Several studies have demonstrated that there is an inverse correlation between adipose tissue linoleic acid content and the risk of coronary heart disease. This led us to consider whether several weight cyclings induced by food restriction followed by regain could affect metabolism of linoleic acid and α-linolenic acid and their longer-chain polyunsaturated fatty acids. Fifty rats were fed a semipurified diet containing 15% fat (30.5% kcal) in which linoleic acid and α-linolenic acid accounted for 7.2 and 3.5% of total fatty acids, respectively. They were randomly divided in two groups. The control (CTL) group was allowed free access to diet whereas the weight-cycled (W-CYC) rats were subjected to four cycles of partial food restriction (24% intake of ad libitum controls, about 5 g/day) for 3 or 4 days to reduce body weight followed by ad libitum refeeding until the weight reached the corresponding average of the CTL group. Four rats were killed as baseline values before weight cycle. The rest of the rats from each group were killed at the beginning ( n = 5), tge end of partial food restriction ( n = 9), and the end of ad libitum refeeding ( n = 10) in weight cycle 4. The fatty acid compositions of the liver, epididymal, and perirenal adipose tissue and carcass were determined by gas liquid chromatography. The W-CYC rats, compared with the CTL rats, increased significantly their food intake immediately after each partial food restriction but thereafter gradually reached that of the CTL. No differences in the weights of liver, epididymal, and perirenal adipose tissue were observed between the W-CYC and CTL group after four weight cycles. Contrary to ad libitum feeding, four weight cyclings decreased the content of linoleic acid in the carcass, epididymal and perirenal adipose tissue. α-linolenic acid was also lower in the W-CYC rats than in the CTL group, but a significant difference was observed only at the end of partial food restriction. Compared with those in the CTL, the liver fatty acids in the W-CYC rats were remarkably modified during the partial food restriction, showing an increase in linoleic, α-linolenic, and arachidonic acids but a decrease in oleic and palmitoleic acids. The food restriction-induced changes in liver fatty acids were reversed after the ad libitum refeeding. We conclude that weight cycling alters body fatty acid composition characterized by a selective decrease in the linoleic acid content of carcass and adipose tissues without significantly changing the total body fat content and the weight of perirenal and epididymal fat pads.

Normal plasma lipoproteins and fertility in gene-targeted mice homozygous for a disruption in the gene encoding very low density lipoprotein receptor.

The very low density lipoprotein (VLDL) receptor is a recently cloned member of the low density lipoprotein (LDL) receptor family that mediates the binding and uptake of VLDL when overexpressed in animal cells. Its sequence is 94% identical in humans and rabbits and 84% identical in humans and chickens, implying a conserved function. Its high level expression in muscle and adipose tissue suggests a role in VLDL triacylglycerol delivery. Mutations in the chicken homologue cause female sterility, owing to impaired VLDL and vitellogenin uptake during egg yolk formation. We used homologous recombination in mouse embryonic stem cells to produce homozygous knockout mice that lack immunodetectable VLDL receptors. Homozygous mice of both sexes were viable and normally fertile. Plasma levels of cholesterol, triacylglycerol, and lipoproteins were normal when the mice were fed normal, high-carbohydrate, or high-fat diets. The sole abnormality detected was a modest decrease in body weight, body mass index, and adipose tissue mass as determined by the weights of epididymal fat pads. We conclude that the VLDL receptor is not required for VLDL clearance from plasma or for ovulation in mice.

Long-term restricted index selection in mice designed to change fat content without changing body size

The objective of this study was to determine if low secondary selection differentials, caused by selecting within full-sib families, may have accounted for the failure of an intended restricted selection index to reduce epididymal fat pad weight (EF) without changing body weight (BW) in mice. Replicate lines that had been selected within full-sib families for high (HE) or low (LE) EF, while holding BW constant, were crossed. After two generations of random mating, two replicates were sampled and selection initiated for the same restricted index criteria except that mass selection was used to increase the selection differentials. In both phases of selection the HE restricted index selection, designed to increase EF without altering BW, was in agreement with expectation. In contrast, the LE index, designed to decrease EF without changing BW, did not agree with theory since BW increased while EF decreased only slightly. Therefore, reduced selection differentials could not explain the deviation from theory. A possible explanation may reside in the restricted selection index being more sensitive to changes in genetic parameters due to shifts in gene frequency as a consequence of the selection applied. However, linkage disequilibrium and genetic drift can not be ruled out as contributing factors to the asymmetry of response.

Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat

Since the type of fat consumed in the diet may play a role in the development of several disorders, it is important to ascertain the effects of different dietary fats upon parameters such as serum lipid levels and adipose deposition. The aim of this study was to determine the effects of feeding rats a range of fats with differing fatty acid compositions. Weanling male rats were fed for 10 weeks on a low fat (LF) diet or on one of five high fat diets, which contained 20% by weight of either hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or menhaden (fish) oil (MO). Food intake, animal growth, tissue weights at sacrifice, serum and liver lipid concentrations and serum, heart, brain and adipose tissue fatty acid compositions were studied. The food intake of the LF-fed animals was greater than that of animals fed on the high fat diets; there were no differences in food intake between animals fed the high fat diets. The total energy intake was lower for animals fed on the HCO diet than for those fed on the LF, OO, EPO or MO diets; there were no other differences in energy intake between the groups. Animals fed the different diets had almost identical rates of weight gain up to 5 weeks; after this period of rapid growth, the increase in weight was slower in all groups but especially in the LF-fed animals. The LF-fed rats had a lower total weight gain and smaller final weights than rats fed on the high fat diets. Animals fed on the MO diet had a greater weight gain than those fed on the OO or EPO diets and their final weights were greater. The MO diet resulted in greatly increased liver weight compared with each of the other diets. The HCO, OO and EPO diets also increased liver weight compared with the LF diet. The total lipid content of the livers from rats fed the high fat diets was greater than that of those from rats fed the LF diet; the livers from animals fed the MO diet contained more lipid than those from animals fed each of the other diets. MO feeding increased the free cholesterol, cholesterol ester and triacylglycerol contents of the liver. Each of the high fat diets resulted in an increase in epididymal fat pad weight compared with the LF diet, but the high fat diets resulted in different degrees of adipose deposition; the EPO and MO diets resulted in smaller epididymal fat pads than the HCO, OO and SO diets. Serum total cholesterol concentrations were higher after feeding the OO, SO or EPO diets than after feeding the LF or MO diets. The MO diet resulted in a total serum cholesterol concentration which was lower than that of animals fed each of the other diets. The serum cholesterol ester concentration of the MO-fed animals was lower than that of the LF-, SO- or EPO-fed animals. Serum triacylglycerol concentrations of the HCO- and OO-fed rats were higher than those of the LF-, SO-, EPO- or MO-fed animals. The fatty acid compositions of the serum, adipose tissue and the neutral lipid and phospholipid fractions of the heart reflected those of the diets themselves, apart from those from the HCO-fed animals, which contained much lower proportions of medium chain fatty acids than did the diet. The fatty acid composition of the phospholipid fraction of the brain was not affected by dietary lipid manipulation. The fatty acid composition of the diet affects animal growth, tissue weights, serum cholesterol, cholesterol ester and triacylglycerol concentrations and the fatty acid compositions of the serum, adipose tissue and heart. The fatty acid composition of the brain is relatively resistant to dietary modification.

Comparison of TOBEC-derived total body fat with fat pad weights

Total body electrical conductivity (TOBEC) predictions of overall body fat were compared to combined perirenal and epididymal fat pad weights. The latter are considered to be reasonable estimates of overall adiposity. TOBEC was used to measure the body composition of 40 male Long-Evans and two male Sprague-Dawley rats ranging in weight from 210–505 g. The animals were then sacrificed and the perirenal and epididymal fat pads were removed and weighed. Core temperature was recorded before and after TOBEC values were collected. To assess the effect of position, two values were obtained for young rats: one when the tail was tucked under the rat's body and another when the tail was extended such that the full length of the measurement chamber was occupied. The TOBEC-predicted body fat was significantly different for these two positions. The best correlation between fat pad weight and TOBEC-predicted body fat ( r = 0.83) was obtained when young animals were in the tail-extended position. The reliability of TOBEC readings appears to be reasonably good with mature rats.

Effect of “Slimax”, a Chinese Herbal Mixture, on Obesity

AbstractThis communication reports the results of biological studies conducted with a phytochemical preparation known as “Slimax” which is an aqueous ethanol extract of the Chinese medicinal plants Polygonum multiflorum, Nephelium longana, Hordeum vulgare, Ligusticum chuanxiong, Lilium brownii, and Rhizoma zingiberis. Results demonstrate that the phytochemical preparation significantly reduced in vivo accretion of adiposity as evaluated by the changes in the weight of epididymal fat pads and the diameter size of fat cells from the treated C57BL/6J obese (ob/ob) mice. Elevated basal levels of blood glucose in obese mice was normalized after chronic treatment with “Slimax”. Glucose oxidation in isolated epididymal fat pads from the treated mice was increased. Biochemical studies further revealed an enhancement of ex vivo lipolytic activity of the isolated adipose tissues from the “Slimax”-treated mice as well as an elevation of plasma levels of fatty acids and glycerol, resulting from the increase of hormon...

Anabolic effects of clenbuterol after long-term treatment and withdrawal in the rat

Injection of rats with the β 2-adrenoceptor agonist clenbuterol (1 mg/kg/d for 15 days) stimulated an increase in body weight (9%) and protein (8%) and water (7%) content, but reduced food intake (4%) and epididymal fat pad mass (39%). Nine days after termination of treatment, ex-clenbuterol rats were heavier (5%) and had a greater protein (7%) and water (6%) content and lower fat pad mass (32%) than controls. Clenbuterol-fed rats (2 mg/kg diet for 10 days, providing an average of 0.04 mg clenbuterol/kg/d) increased body weight (7%), muscle mass (15% to 21%), and muscle protein content (9% to 26%), whereas epididymal fat pad weight and muscle glycogen content were reduced. During the withdrawal period, the greater body weight of ex-clenbuterol rats was sustained overall (ANOVA, P < .00005), but by day 10 this difference was no longer significant. At this point, gastrocnemius muscle mass was still higher (11%) when compared with that of control animals, but soleus muscle mass, muscle glycogen concentration, and epididymal fat pad weight had reverted to control values. These results were corroborated in a subsequent experiment using older rats. It was concluded that, unlike other β-adrenoceptor-mediated effects, muscle protein accumulated during clenbuterol treatment can be maintained in certain muscles after removal of the drug for a period of time that is at least equivalent to the duration of treatment. This could have implications for the potential therapeutic use of this class of compound, and differences in the response observed between muscle types may help to elucidate the mechanisms responsible for the muscle protein deposition induced by clenbuterol.

Time course of adaptation to a high-fat diet in obesity-resistant and obesity-prone rats

The purpose of the present study was to characterize the time course of adaptation (i.e., circulating metabolites and hormones, fat pad mass, lipoprotein lipase) to a high-fat diet in obesity-prone (OP) and obesity-resistant (OR) male Wistar rats. Delineation of OP and OR was based on body weight gain (upper tertile for OP; lower tertile for OR) after 1 wk on a high-fat diet (60% of kcal from corn oil). Rats were killed after 1, 2, or 5 wk of the dietary period. Increased body weight and percent body fat in OP rats at 1 wk could not be accounted for by increased retroperitoneal or epididymal fat pad weight. Plasma nonesterified fatty acids and triglycerides, as well as blood concentrations of glucose, lactate, and glycerol, were similar throughout the study. Plasma insulin was significantly greater in OP vs. OR rats and low-fat diet (LFD; 20% of kcal from corn oil) controls at 5 wk only, and blood beta-hydroxybutyrate (mM) was significantly higher in OR compared with OP and LFD rats at 1, 2, and 5 wk. Lipoprotein lipase mRNA and activity were significantly greater in epididymal fat pad and significantly lower in gastrocnemius muscle of OP vs. OR rats at 1 wk. Results suggest that early (i.e., 1 wk) differences in body weight and fat weight between OP and OR rats are not due to fat deposition in retroperitoneal or epididymal fat depots, and tissue-specific changes in LPL (increase in epididymal fat pad and decrease in gastrocnemius muscle) that occur in OP compared with OR rats after 1 wk on a high-fat diet provide a metabolic environment favoring fat storage.

Effect of cryoprotectant and genetic selection for body fat content on embryonic cryosurvival in mice

Lines of mice selected for high (HF) or low (LF) 12-week epididymal fat pad weight as a percentage of body weight were used to investigate the effects of genotype, two cryoprotectants [glycerol (GLY) and propylene glycol (PG)] and genotype x cryoprotectant interaction on cryosurvival of four and eight-cell embryos. Embryos were collected from selection lines and reciprocal crosses of selection lines (HFLF and LFHF) and frozen by established slow-cool methods. Embryos were thawed for 40s at room temperature and then placed in a 37° C waterbath for 1 min. Cryoprotectant was diluted from embryos with either 0.5 M sucrose (GLY-treated) or 1.0 M sucrose (PG-treated). Post-thaw survival was measured as the percentage of embryos developing to 36 h (PTS36), 48 h (PTS48) and hatched blastocyst (PTSHB), respectively. Non-frozen controls were cultured concurrently with frozen embryos. No significant genotype or genotype x cryoprotectant interaction effects were found. Results of the embryo freezing study indicated that selection for high or low fat content did not affect the ability of embryos to survive cryopreservation. There was no indication of embryo heterosis for post-thaw survial. Embryos frozen with GLY survived the freeze-thaw stress significantly better than those frozen in PG (P < 0.05). In vitro development of non-frozen controls at 36 and 48 h did not vary significantly among lines, but in vitro development was significantly different among lines at the hatched blastocyst stage (P < 0.05). Linear contrasts showed that the embryonic genome was responsible for differential in vitro development at the hatched blastocyst stage between these selected lines (HF > LF; P < 0.05); asymmetric response also occurred in that both HF and LF exceeded the unselected control line (P < 0.05).

Comparison of body weight and adipose tissue in male C57BI/6J mice fed diets with and withouttrans fatty acids.

The effect of a diet containingtrans-fatty acids (tFA) on the fatty acid composition and fat accumulation in adipose tissue was investigated in mice. Male C57BI/6J mice were fed Control or Trans Diets that were similar, except that 50% of the 18∶1, which was allcis in the Control Diet, was replaced bytFA in the Trans Diet. At selected ages, body weight, epididymal fat pad weight, perirenal fat yield, adipose tissue cellularity and fatty acid composition were examined. Over the time period studied (2-24 mon), the proportion of 18∶0 and 16∶0 tended to decrease whilecis-18∶1 levels increased. Compared to the Control Diet, the Trans Diet resulted in adipose tissue lipids with higher percentages of 14∶0 and 18∶2n-6 and lower percentages ofcis-18∶1 and 20∶4n-6. In polar lipids,tFA replaced saturated fatty acids, whereastFA replacedcis-18∶1 in the nonpolar lipids. Body weights at 16 and 24 mon of age and epididymal fat pad weights at 8-24 mon of age were lower in mice fed the Trans Diet as compared to those fed the Control Diet. At the ages studied, the Trans Diet also resulted in lower values for perirenal fat weights, triacylglycerol to polar lipid ratios, and adipose cell size. The data suggest that chronic consumption oftFA affects lipid metabolism and results in decreased fat accumulation in murine adipose tissue.

Regulation of hormone-sensitive lipase during fasting

Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysis. The activity of HSL is thought to be primarily regulated by phosphorylation-dephosphorylation reactions. Although FFA levels are elevated during fasting, it has been difficult to demonstrate an increase in HSL activity with fasting. The current studies were undertaken to explore directly the regulation of HSL expression in adipose tissue in the rat during fasting. Rats were fasted for periods up to 5 days and HSL activity, HSL immunoreactive protein, and HSL mRNA levels were measured both in intact epididymal adipose tissue and in isolated adipose cells. Fasting caused a progressive decline in total body weight and the weight of epididymal fat pads, whereas adipose cell size decreased approximately 50% after 2 days of fasting. Serum FFA levels approximately doubled within 1 day of fasting and remained elevated thereafter. Basal lipolysis, measured as glycerol release, did not increase until 2 days of fasting. HSL activity remained relatively unchanged until 3 days of fasting when it was increased twofold after 3-5 days of fasting. Likewise, HSL immunoreactive protein and HSL mRNA levels increased twofold after 3-5 days of fasting. Thus HSL activity appears to be regulated by pretranslational mechanisms during prolonged fasting. However, increases in FFA flux during short-term fasting appear to involve either post-translational control of HSL or the regulation of other enzymes.

Chronic cerebroventricular galanin does not induce sustained hyperphagia or obesity

Acute central administration of galanin has been reported to increase fat consumption. These experiments were designed to test the hypothesis that repeated injections of galanin would elicit hyperphagia and weight gain and that this response would depend on the available diet. Male Sprague-Dawley rats were fed high (56% energy) or low (10% energy) fat diets. Galanin (300 pmol) or saline vehicle was injected into the third ventricle twice daily for 7 days and three times daily for another 6 days. On both the high-carbohydrate and high-fat diets, twice daily galanin increased daytime food intake, but there was a compensatory decrease in nighttime intake. The addition of a third, nighttime injection of galanin was ineffective in producing an increase in total 24-h intake. There was no significant increase in body weight during galanin treatment in rats eating either diet although animals eating the high-fat diet gained more weight as reflected by a significant increase in epididymal fat pad weight. Galanin treatment had no effects on serum insulin, glucose or corticosterone concentrations, measured at the end of the experiment. However, animals fed the high-fat diet had significantly higher insulin concentrations at the time of sacrifice. Although repeated central infusions of galanin reliably stimulated daytime intake of both diets, they failed to increase total daily energy intake or body weight.

Effect of Voluntary Exercise on 3'-Methyl-4-Dimethylaminoazobenzene-lnduced Hepatomas in Male Jc1: Wistar Rats

The effect of voluntary exercise on 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB)-induced hepatomas was investigated in male Jc1:Wistar rats. Beginning at 10 weeks of age, animals were divided into two groups (sedentary and exercise) and housed in individual cages. Food intake and wheel exercise were automatically controlled in the cages of the exercise group. Body weights were monitored throughout the study. Food availability was controlled in order to equate length and weight gain. From 27 weeks to termination of the study at 62 weeks, all animals were administered 3'-Me-DAB in the diet at a dose level of 0.0177 g/day/kg body wt. All animals were sacrificed at 62 weeks of age. The incidence of hepatomas was significantly lower in the exercise group as compared with the sedentary group (0% and 65%, respectively). Liver weight was significantly greater in the exercise group compared with sedentary animals without hepatomas. The weight of epididymal fat pads was significantly lower in the exercise group. Serum alkaline phosphate was significantly higher in the exercise group as compared with the sedentary group. Serum gamma-glutamyl-transpeptidase levels were higher in the sedentary group than in the exercise group. In addition, gamma-glutamyl-transpeptidase levels were significantly higher in sedentary animals with hepatomas than in sedentary animals without hepatomas. These results demonstrate that voluntary exercise decreases 3'-Me-DAB-induced hepatomas and that this decrease is associated with an increase in serum alkaline phosphatase and a decrease in serum gamma-glutamyl-transpeptidase levels.

Size distribution of adipocytes and variation in adipocyte number in lines of mice selected for high or low body fat

1. 1. Adipocyte size and number were measured in epididymal fat pads from lines of mice selected for high or low body fat. 2. 2. Epididymal fat pad weight at 10 weeks of age was 4-fold greater in the high fat than the low fat mice, accompanied by a 7-fold greater adipocyte volume but there was no difference in adipocyte number. Smaller differences in fatness and cell volume were observed at younger ages. 3. 3. The high fat mice showed one or two populations of cells up to 5 weeks of age and at 7 weeks 3 days and 10 weeks showed two or more populations. In contrast, the low fat animals at all ages showed either one or two populations. 4. 4. These findings imply that greater lipogenesis and cell filling, not cell proliferation, is the primary mechanism of increased fatness in these selected lines of mice.

Restricted selection index in mice designed to change body fat without changing body weight: correlated responses

Correlated responses were studied in lines of mice selected for eight generations based on the criterion of a restricted selection index. Two replicate lines were selected in each treatment as follows: HE, high epididymal fat pad weight (EF) with zero change in body weight (BW) at 12 weeks of age; LE; low EF with zero change in BW; and RS, randomly. Correlated responses showed considerable variation between replicates, suggesting that genetic drift was important. Further, correlated responses for most traits were relatively small, probably because of low selection intensity. The HE line responded as expected in component traits of the restricted index. Associated compositional traits in HE responded as predicted since traits correlated with adiposity increased and hind carcass weight did not change significantly. Feed intake increased and feed efficiency (weight gain/feed intake) decreased in HE, as predicted. In contrast, the LE line did not respond in component traits as predicted since EF did not decrease and BW increased. Consequently, LE exhibited little change in traits associated with adiposity, but hind carcass weight, feed intake and feed efficiency increased. Of the correlated responses scored for fitness traits (littering rate, number of days from pairing of mate to littering, litter size and preweaning pup survival rate), significant effects were found for decreased littering rate in LE and increased prenatal survival rate in HE. In summary, correlated responses to restricted index selection generally agreed with expectation when responses in component traits of the index were considered.

Restricted index selection in mice designed to change body fat without changing body weight: direct responses

Replicated within full-sib family restricted index selection was conducted for eight generations in mice for high or low epididymal fat pad weight (EF) holding body weight (BW) constant. Pooled realized heritability estimates of index units based on high, low and divergent selection were 0.42±0.20, 0.44±0.19 and 0.42± 0.05, respectively, which were not different from the base population estimate of 0.33±0.10. Realized responses per generation pooled across replicates in the high-fat restricted index lines were in the expected directions for EF (17.5±7.2 mg; P<0.05) and BW (0.03±0.58 g; P>0.05), but responses in the low-fat restricted index lines were discrepant for EF (0.3±5.1 mg; P>0.05) and BW (0.38±0.01 g; P<0.01). Consequently, the realized responses in component traits were decidedly asymmetric (P<0.05). A technique for estimating realized genetic parameters from index selection lines gave realized heritabilities for BW and EF of 0.68±0.04 and 0.45±0.05, respectively, and a realized genetic correlation between BW and EF of 0.93±0.01 compared with base population estimates of 0.43±0.08, 0.49±0.10 and 0.78±0.05, respectively. Possible explanations for the disparity between observed and expected responses in the low-fat restricted index lines include genetic drift, poor estimates of base population parameters, changes in genetic parameters with selection, linkage disequilibrium resulting from selection and asymmetric realized relative index weights.