Influence of dietary conjugated linoleic Acid and fat source on body fat and apoptosis in mice

OBJECTIVE: To determine whether altered dietary essential fatty acid (linoleic and arachidonic acid) concentrations alter sensitivity to conjugated linoleic acid (CLA)-induced body fat loss or DNA fragmentation. RESEARCH METHODS AND PROCEDURES: Mice were fed diets containing soy oil (control), coconut oil [essential fatty acid deficient (EFAD)], or fish oil (FO) for 42 days, and then diets were supplemented with a mixture of CLA isomers (0.5% of the diet) for 14 days. Body fat index, fat pad and liver weights, DNA fragmentation in adipose tissue, and fatty acid profiles of adipose tissue were determined. RESULTS: The EFAD diet decreased (p < 0.05) linoleic and arachidonic acid in mouse adipose tissue but did not affect body fat. Dietary CLA caused a reduction (p < 0.05) in body fat. Mice fed the EFAD diet and then supplemented with CLA exhibited a greater reduction (p < 0.001) in body fat (20.21% vs. 6.94% in EFAD and EFAD + CLA-fed mice, respectively) compared with mice fed soy oil. Dietary FO decreased linoleic acid and increased arachidonic acid in mouse adipose tissue. Mice fed FO or CLA were leaner (p < 0.05) than control mice. FO + CLA-fed mice did not differ in body fat compared with FO-fed mice. Adipose tissue apoptosis was increased (p < 0.001) in CLA-supplemented mice and was not affected by fat source. DISCUSSION: Reductions in linoleic acid concentration made mice more sensitive to CLA-induced body fat loss only when arachidonic acid concentrations were also reduced. Dietary essential fatty acids did not affect CLA-induced DNA fragmentation.     

Conjugated linoleic acid persistently increases total energy expenditure in AKR/J mice without increasing uncoupling protein gene expression

AKR/J mice fed a high fat diet were treated with a 1% (1 g/100 g) admixture of conjugated linoleic acids (CLA) for 5 wk and compared with control mice. Body weights, energy intakes and energy expenditure (EE) determined by indirect calorimetry were measured weekly. CLA treatment reduced adipose depot weights by approximately 50% but had no significant effects on either body weight or energy intake. CLA increased EE persistently by an average of 7.7% throughout the 5-wk experiment. This greater EE, despite no difference in energy intake, was sufficient to account for the lower body fat stores in the CLA-treated mice. De novo fatty acid biosynthesis in adipose tissue, measured by incorporation of deuterium-labeled water, was not decreased by CLA treatment and therefore did not explain the lower adipose lipid in these mice. Expression of uncoupling protein (UCP) in skeletal muscle, white adipose tissue and kidney was not affected by CLA treatment. In brown adipose tissue, UCP1 expression was not affected by CLA treatment. However, UCP2 expression, although quite low, was significantly greater in CLA-fed mice. We conclude that CLA acts to reduce body fat stores by chronically increasing metabolic rate. This effect on metabolic rate is likely not due to increased UCP gene expression. Furthermore, the reduced body fat is not due to decreased de novo fatty acid synthesis in white adipose tissue.     

Conjugated linoleic acid affects lipid composition, metabolism, and gene expression in gilthead sea bream (Sparus aurata L)

To maximize growth, farmed fish are fed high-fat diets, which can lead to high tissue lipid concentrations that have an impact on quality. The intake of conjugated linoleic acid (CLA) reduces body fat in mammals and this study was undertaken to determine the effects of dietary CLA on growth, composition, and postprandial metabolic variables in sea bream. Fish were fed 3 diets containing 48 g/100 g protein and 24 g/100 g fat, including fish oil supplemented with 0 (control), 2, or 4% CLA for 12 wk. Feed intake, specific growth rate, total body fat, and circulating somatolactin concentration were lower in fish fed CLA than in controls. Feed efficiency was greater in fish fed 2% CLA than in controls. Liver triglyceride concentrations were higher in fish fed 4% CLA and muscle triglyceride concentrations were lower in fish fed both CLA diets than in controls. Hepatic fatty acyl desaturase and elongase mRNA levels in fish fed CLA were lower than in controls. Metabolic differences between controls and CLA-fed fish were observed at 6 h but not at 24 h after the last meal, including lower postprandial circulating triglyceride concentrations, higher hepatic acyl-CoA-oxidase, and lower L-3-hydroxyacyl-CoA dehydrogenase activities in CLA-fed fish than in controls. Dietary CLA did not affect enzymes involved in lipogenesis including hepatic fatty acid synthase and malic enzyme, but it decreased glucose 6-phosphate dehydrogenase activity at 24 h, but not at 6 h after feeding. The data suggest that CLA intake in sea bream has little effect on hepatic lipogenesis, channels dietary lipid from adipose tissue to the liver, and switches hepatic mitochondrial to peroxisomal beta-oxidation.     

共轭亚油酸强化乳对小鼠体脂及血脂的影响

目的:探讨共轭亚油酸(CLA)强化乳对小鼠体脂及血脂的影响。方法:选4w龄的雄性昆明种小鼠40只,随机分成四组,每组10只,分别在牛奶中添加0%、0.1%、0.5%、1.0%的CLA喂养小鼠4w后,测定体重、腹脂重、体脂含量、饲料利用率及血浆甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇含量(HDL)与脂蛋白脂酶(LPL)活性。结果:小鼠的体增重、腹脂重、体脂含量及饲料利用率都随着乳中CLA的添加量增加而降低,与对照组比,当添加0.5%时达到显著差异;在乳中添加CLA可以降低小鼠血浆中的TG与TC含量,提高HDL含量和LPL活性,降低动脉硬化指数(TC-HDL/HDL)。TC含量在添加0.5%CLA时最低,其它的血脂指标在添加1.0%CLA时效果最好。结论:共轭亚油酸强化乳有降低体脂和血脂的作用。     

Modulation of body fat and serum leptin levels by dietary conjugated linoleic acid in Sprague-Dawley rats fed various fat-level diets

OBJECTIVES: In this study, we examined the effect of dietary conjugated linoleic acid (CLA) on body fat levels in Sprague-Dawley rats. METHODS: Rats were fed AIN-93G type diets containing 4%, 7%, and 10% fats with or without 1.5% CLA. RESULTS: Three weeks after the onset of the experimental period, the weights of perirenal white adipose tissue were lower in CLA-fed rats. The weights of epididymal white adipose tissue also were lower in CLA-fed rats than in control rats, but this effect disappeared with increased dietary fat level. Serum leptin levels tended to be lower in the CLA group, especially the low-fat diet group, than in the control group. There were significant positive correlations between serum leptin level and weights of perirenal and epididymal white adipose tissues in control groups, but these correlations were weaker in the CLA groups. Serum tumor necrosis factor-alpha levels also tended to be lower in CLA-fed rats, and this tendency was most remarkable in the rats fed 7% fat diets. CONCLUSION: In conclusion, dietary CLA, especially the low-fat diet, reduced body fat without hepatic injury to Sprague-Dawley rats.     

Adrenalectomy reduces adiposity by decreasing food efficiency, not direct effects on white adipose tissue.

OBJECTIVE: This study was conducted to establish the effects of adrenalectomy (ADX) on adipose tissue metabolism in male Sprague-Dawley rats fed a standard chow diet. RESEARCH METHODS AND PROCEDURES: The effects of adrenalectomy on adipose cell size, lipoprotein lipase activity, and basal and insulin-stimulated glucose conversion to lipid and lipolysis were measured. RESULTS: ADX decreased body weight gain during the post-operative period in the absence of changes in food intake; feed efficiency was decreased significantly. ADX decreased adipocyte size by 30%. ADX increased adipocyte response to the effect of submaximal concentrations of insulin on lipid synthesis and lipolysis. ADX decreased maximally insulin-stimulated lipid synthesis, but this effect was accounted for by decreased adipocyte size. In contrast, ADX had no effect on maximally insulin-inhibited lipolysis. ADX did not affect heparin-releasable LPL. The small effect of ADX on residual extractable adipose tissue LPL activity was accounted for by decreased fat cell size. DISCUSSION: ADX decreased adiposity in the absence of changes in food intake, lipoprotein lipase activity, and adipocyte lipid metabolism. The effect is best attributed to decreased feed efficiency.     

Incorporation of conjugated linoleic acid into brain lipids is not necessary for conjugated linoleic acid–induced reductions in feed intake or body fat in mice

Dietary conjugated linoleic acid (CLA) causes reduced feed intake (FI) and body fat (BF). It is unknown, though, if CLA incorporation into tissues, alterations in serum hormones, and/or appetite-regulating neuropeptides are involved. We hypothesized that CLA incorporation into brain lipids would be correlated with changes in appetite-regulating neuropeptide expression and reductions in FI and BF. Male mice (n = 150; 9 weeks old, ICR) received the control diet ad libitum (CON), 2% CLA diet ad libitum (CLA), or control diet pair-fed to the intake of CLA-fed mice for 1, 2, 3, 5, or 7 days. Both FI and body weight were measured daily, and a BF index was calculated. Liver, adipose, and brain fatty acids; serum insulin, leptin, and peptide YY; and arcuate nucleus neuropeptide Y, agouti-related protein, and α-melanocyte–stimulating hormone protein were determined. Mice fed CLA ate less (P < .05) than did the CON on days 1, 2, 3, and 7 but were leaner (P < .05) only on day 7. Mice that received the control diet pair-fed to the intake of CLA-fed mice did not differ in BF from the CON. By days 1 and 2, CLA isomers were incorporated into the liver and adipose but not in the brain. Insulin was increased in CLA-fed mice on days 5 and 7, and leptin was decreased on day 7. Peptide YY and the neuropeptides did not differ. Tissue CLA was not correlated with FI, body weight, or BF but was positively correlated with insulin and negatively correlated with leptin. The reduction in FI is not sufficient to cause the reduction in BF, and tissue CLA accumulation does not appear to be required.     

Hepatic steatosis is not due to impaired fatty acid oxidation capacities in C57BL/6J mice fed the conjugated trans-10,cis-12-isomer of linoleic acid

Decreased body fat mass and liver steatosis have been reported in mice fed diets containing the conjugated linoleic acid trans-10,cis-12-C18:2 (CLA2), but not in those fed diets containing cis-9,trans-11-C18:2 (CLA1). Because the decrease in fatty acid (FA) oxidation may cause fat accumulation, we questioned whether the effects of both CLAs on enzyme activities and mRNA expression were related to liver FA oxidation. To address this question, 7-wk-old male C57BL/6J mice were fed for 4 wk a diet supplemented with 1% CLA1, CLA2, or cis-9-C18:1 (control) esterified as triacylglycerols. In CLA2-fed mice, the proportions of CLA2 in the total FA of liver lipids were substantially lower than those of CLA1 in mice fed CLA1. The mitochondrial protein content per total liver was about 56% greater in CLA2-fed mice than in CLA1-fed mice and controls. Mitochondrial carnitine palmitoyltransferase I (CPT I) and carnitine-dependent palmitate oxidation activities were also significantly greater in CLA2-fed mice than in the two other groups. The amounts of malonyl-CoA per gram of liver and the sensitivity of CPT I to malonyl-CoA inhibition were greater in both groups of CLA-fed mice than in the controls. L-CPT I mRNA expression doubled in CLA2-fed mice and was 3 and 2 times greater for M-CPT I in the CLA1 and CLA2 groups, respectively, compared with controls. Peroxisomal FA oxidation-related activities and acyl-CoA oxidase mRNA expression were increased in CLA1-fed mice, and to a larger extent in CLA2-fed mice, relative to controls. These data indicate that FA oxidation capacities were increased in mice fed CLA2, but were likely depressed in vivo through malonyl-CoA inhibition.     

Dietary conjugated linoleic acid reduces rat adipose tissue cell size rather than cell number

We investigated the basis for the reduction in fat pad size in rats fed conjugated linoleic acid (CLA). In the first study, growing female Sprague-Dawley rats (initial weight150 g) were fed diets containing 0, 0.25 and 0.5 g/100 g diet of a purified (97% CLA) and 0.5% of a feed-grade (55% CLA) source of CLA for 5 wk to determine the effects on growth performance and fat mass. There was no effect of CLA on growth rate or food intake. Dietary CLA reduced retroperitoneal fat pad weight 13, 25 and 32% in rats fed 0.25 and 0. 5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.05). Similar effects were observed in the parametrial fat pad. The reduced pad size was due to smaller adipocyte size rather than a reduced cell number. Relative to the control group, mean cell volume was 15, 28 and 29% lower in tissue from rats fed 0.25 and 0.5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.01). In the second study, rats were fed CLA (0 vs. 0.5%) for 7 or 49 d. Reductions in fat pad weight were observed within 7 d. In addition, the effects of CLA on energy metabolism were studied in the chronically fed rats. There were no significant effects of CLA on oxygen consumption, CO(2) or heat production. During wk 4 of feeding, but not at other times, there was a 5% lower respiratory quotient in CLA-fed rats (P < 0.05). There was a time-dependent accumulation of CLA in adipose tissue and a decrease in monounsaturated fatty acids. These results suggest that the reduction in fat mass in rats fed CLA can be accounted for by a reduction in cell size rather than a change in cell number.     

Trans-10, cis-12-conjugated linoleic acid does not increase body fat loss induced by energy restriction

Very little evidence exists concerning the effects of conjugated linoleic acid (CLA) on body fat reduction induced by energy restriction. Moreover, although an effect of trans-10, cis-12-CLA on lipolysis has been suggested, it has not been consistently shown. The aims of the present study were to determine whether trans-10, cis-12-CLA increases the reduction of body fat induced by energy restriction, and to analyse its effect on lipolysis and adipose tissue lipase expression (hormone-sensitive lipase (HSL) and adipose tissue TAG lipase (ATGL)). Male Syrian Golden hamsters were fed a high-fat diet during 7 weeks in order to make them fatter. Then they were submitted to a mild energy restriction (25 %) without or with supplementation of 0.5 % trans-10, cis-12-CLA for 3 weeks. Basal glycerol release and lipolysis stimulated by several drugs acting at different levels of the lipolytic cascade were measured in epididymal adipose tissue. The expression of HSL and ATGL was assessed by real-time RT-PCR. No differences were found in adipose tissues size between the experimental groups. Medium adipocyte size and total number of adipocytes were similar in both experimental groups. Animals fed the CLA-enriched diet showed similar lipolytic rates as well as HSL and ATGL expressions to the controls. In conclusion, trans-10, cis-12-CLA does not promote adipose tissue lipid mobilisation nor does it heighten body fat reduction induced by energy restriction. Consequently, this CLA isomer does not seem to be a useful tool to be included in body weight-loss strategies followed in obesity treatment.     

Short-term feeding of conjugated linoleic acid does not induce hepatic steatosis in C57BL/6J mice

We investigated the effect of short-term feeding of conjugated linoleic acid (CLA) on adipose tissue weights, liver weight, hepatic lipid metabolism, and serum lipoprotein profiles in C57BL/6J mice. Mice were fed semi-synthetic diets containing either 6%, high-linoleic safflower oil (HL-SAF) or 4% HL-SAF+2% CLA for 1 wk. Short-term feeding of CLA showed an anti-obesity effect without inducing hepatomegaly in mice. In addition to the decline of hepatic triglyceride concentration, significant inhibition of A9 desaturation of fatty acid in the total liver lipids was found in CLA-fed mice. The CLA diet significantly increased the activities of peroxisomal beta-oxidation and decreased the activities of diacylglycerol acyltransferase, a triglyceride synthesis-related enzyme, in the liver. Moreover, serum lipoprotein profiles of CLA-fed mice showed preferable changes in the atherogenic indices. However, serum leptin and adiponectin were drastically decreased by CLA feeding, suggesting that prolonged administration of CLA would induce further decrease of serum adipocytokine levels, which may be a cause of lipodystrophy in mice. These results show that short-term feeding of CLA does not induce adverse effect in C57BL/6J mice.     

Pre- and postnatal dietary conjugated linoleic acid alters adipose development, body weight gain and body composition in Sprague-Dawley rats

Sprague-Dawley rats were fed either a control diet (7 g/100 g soybean oil) or a conjugated linoleic acid (CLA) diet (6.5 g/100 g soybean oil and 0.5 g/100 g CLA) beginning on d 7 of gestation to determine whether pre- and postnatal CLA affects short- and long-term growth and adiposity. At weaning (d 21), progeny were assigned control or CLA diet and fed until 11 wk of age. At birth, litter size and weight were not different between treatments. There were age- and sex-dependent changes in inguinal adipose fatty acid composition at birth and weaning, whereas there were no differences in lipid accretion or adipocyte proliferation. At weaning, CLA did not alter inguinal adipocyte proliferation but increased (P < 0.01) CCAAT/enhancer binding protein alpha expression in inguinal adipose tissue from females, whereas there was no difference in expression in males. Significant differences in size distribution of inguinal adipocytes at weaning and retroperitoneal adipocytes at 11 wk of age were observed. In general, CLA increased the proportion of smaller cells and decreased the proportion of larger cells. The main long-term effect of the dams' diet was the significantly heavier gastrocnemius and soleus muscles, and significantly longer tail lengths, an indication of skeletal growth, of male pups whose dams were fed CLA. Postweaning diet reduced fat pad weights in female but not male pups fed CLA. This response was due to differences in cell size rather than number. Response to CLA treatment may depend on the sex and age of the animal as well as duration of feeding.     

Effect of dietary conjugated linoleic acid on body composition and energy balance in broiler chickens

The effect of dietary conjugated linoleic acid (CLA) on body composition and energy metabolism was investigated in broiler chickens. Male broiler chicks were assigned to receive either a control diet (1 % sunflower oil) or a diet containing CLA (1 % of a 1:1 mixture of trans-10, cis-12 and cis-9, trans-11 isomers of octadecadienoic acid). The diets were fed ad libitum for 3 weeks and there were eight replicates per diet, each replicate including four chickens so that each treatment had thirty-two animals. The proportion of body fat was lower in the control group than in the CLA group. No significant differences as to the proportions of body water, ash and protein were observed. Feed and energy intake were significantly lower in CLA-fed birds. The percentage of ingested energy lost in excreta was higher after CLA feeding and heat expenditure as a percentage of ingested energy was lower in the CLA-fed group. The CLA-fed group showed a higher percentage of SFA and lower percentages of MUFA and PUFA in carcass fat. It is concluded that CLA stimulated de novo fatty acid synthesis and lowered desaturase activity.     

Conjugated linoleic acid differentially modifies fatty acid composition in subcellular fractions of muscle and adipose tissue but not adiposity of postweaning pigs

This study examined the interaction between conjugated linoleic acid (CLA) and dietary fat type on the enrichment of subcellular fractions, the Delta(9) desaturase index and adiposity in pigs. Early weaned piglets (n = 6/group) were fed for 35 d diets supplemented with 15 g/100 g diet beef tallow or corn oil, or 12 g/100 g tallow or corn oil plus 3 g CLA. There were no effects of dietary fat or CLA on the mass of dissected skin, bone, muscle or adipose tissue of the 7th to 9th thoracic rib sections. Medial subcutaneous adipose tissue of pigs fed tallow had smaller adipocytes than that of pigs fed corn oil. The lateral subcutaneous site was unaffected by dietary fat type. Microsomes accumulated <50% the concentration of trans-10,cis-12, cis-11,trans-13, and cis-9,trans-11 CLA as membrane and nonmembrane fractions of adipose tissue and longissimus muscle. There was no evidence of preferential incorporation of any CLA isomer into any of the subcellular fractions. Addition of CLA to the diets reduced adipose tissue nonmembrane monounsaturated fatty acids (MUFA; g/100 g total fatty acids) by 15% in corn oil-fed pigs and by 19% in tallow-fed pigs. Total saturated fatty acids (SFA) were increased by CLA commensurately in this lipid fraction. This resulted in a reduced Delta(9) desaturase index [MUFA/(SFA + MUFA)] in the nonmembrane lipid fraction of pigs fed either the corn oil or tallow diets. Thus, in spite of marked effects on fatty acid composition and the Delta(9) desaturase index, CLA had no effect on adiposity in early weaned piglets fed high fat diets.     

Dietary fish oil increases lipid mobilization but does not decrease lipid storage-related enzyme activities in adipose tissue of insulin-resistant,sucrose-fed rats

Fish oil feeding has been shown to limit visceral fat accumulation in insulin-resistant rats. Our goal was to determine whether this finding is due to increased fat mobilization or decreased lipid storage. Adipocytes were isolated from rats fed for 3 wk a diet containing 57.5 g/100 g sucrose and 14 g/100 g lipids as either fish oil (SF) or a mixture of standard oils (SC); there was also a reference group (R). Substituting fish oil for standard oils protected rats from visceral fat hypertrophy, hypertriglyceridemia and hyperglycemia. The stimulation of lipolysis was greater in adipocytes isolated from SF-fed rats than in those from SC-fed rats. Fatty acid synthase (FAS) activity was markedly lower in the liver but not in the adipose tissues of rats fed SF. Lipoprotein lipase (LPL) activity was 2.2-fold higher in the adipose tissues but not in the muscle in rats fed the SF diet than in those fed the SC diet. The decrease in visceral fat in rats fed fish oil could be attributed to decreased plasma triacylglycerol concentration and/or increased lipid mobilization rather than to reduced lipid storage.     

Serum leptin concentrations are not related to dietary patterns but are related to sex, age, body mass index, serum triacylglycerol, serum insulin, and plasma glucose in the US population

Background

The conjugated linoleic acid (CLA) content of beef can be increased by supplementing appropriate beef cattle diets with vegetable oil or oil seed. Yet the effect of consumption of such beef on adipose tissue characteristics is unclear, thus the study was conducted to compare adipose tissue responses of rats to diets containing beef from steers either not provided or provided the oil supplements to alter CLA composition of the fat in muscle.

Methods

Effects of feeding synthetic (industrial hydrogenation) CLA or CLA from beef on growth and adipose tissue responses of weanling, male, Wistar rats (n = 56; 14 per treatment diet) were investigated in a completely randomized design experiment. Diets were: control (CON) diet containing casein and soybean oil, synthetic CLA (SCLA) diet; where 1.69% synthetic CLA replaced soybean oil, two beef-diets; CONM and CLAM, containing freeze dried beef from steers either not fed or fed 14% sunflower seeds to increase CLA content of beef. Diets were isonitrogenous (20% protein) and isocaloric. Rat weights and ad libitum intakes were recorded every 2 wk. After 9 wk, rats were fasted for 24 h, blood sampled by heart puncture, sacrificed, tissue and organs were harvested and weights recorded. The adipose tissue responses with regard to cellularity and fatty acid compositions of retroperitoneal and inguinal adipose tissue were determined.

Results

Body weights and gains were comparable, but organ weights as percent of body weight were greater for rats fed SCLA than CONM. Fasting blood glucose concentration was lower (p < 0.01) in rats fed SCLA than those fed CONM or CLAM. Retroperitoneal and inguinal fat weights, as percent of body weight were greater (p < 0.01) in rats fed CONM or CLAM than those fed CON or SCLA diets. Adipocyte numbers were least in retroperitoneal tissue of rats fed SCLA, while inguinal tissue cell density and total number were lower (p = 0.02) in rats fed CLAM (7.26 × 10⁷ cells/g and 8.03 × 10⁸ cells) than those fed CONM (28.88 × 10⁷ cells/g and 32.05 × 10⁸ cells, respectively).

Conclusion

Study suggests that dietary CLA either as synthetic or high CLA-beef may alter adipose tissue characteristics by decreasing the number of adipocytes and by decreasing the size of the tissue.     

CLA-enriched diet containing t10,c12-CLA alters bile acid homeostasis and increases the risk of cholelithiasis in mice

Mice fed a mixture of CLA containing t10,c12-CLA lose fat mass and develop hyperinsulinemia and hepatic steatosis due to an accumulation of TG and cholesterol. Because cholesterol is the precursor in bile acid (BA) synthesis, we investigated whether t10,c12-CLA alters BA metabolism. In Expt. 1, female C57Bl/6J mice were fed a standard diet for 28 d supplemented with a CLA mixture (1 g/100 g) or not (controls). In Expt. 2, the feeding period was reduced to 4, 6, and 10 d. In Expt. 3, mice were fed a diet supplemented with linoleic acid, c9,t11-CLA, or t10,c12-CLA (0.4 g/100 g) for 28 d. In Expt. 1, the BA pool size was greater in CLA-fed mice than in controls and the entero-hepatic circulation of BA was altered due to greater BA synthesis and ileal reclamation. This resulted from higher hepatic cholesterol 7α-hydroxylase (CYP7A1) and ileal apical sodium BA transporter expressions in CLA-fed mice. Furthermore, hepatic Na(+)/taurocholate co-transporting polypeptide (NTCP) (-52%) and bile salt export pump (BSEP) (-77%) protein levels were lower in CLA-fed mice than in controls, leading to a greater accumulation of BA in the plasma (+500%); also, the cholesterol saturation index and the concentration of hydrophobic BA in the bile were greater in CLA-fed mice, changes associated with the presence of cholesterol crystals. Expt. 2 suggests that CLA-mediated changes were caused by hyperinsulinemia, which occurred after 6 d of the CLA diet before NTCP and BSEP mRNA downregulation (10 d). Expt. 3 demonstrated that only t10,c12-CLA altered NTCP and BSEP mRNA levels. In conclusion, t10,c12-CLA alters BA homeostasis and increases the risk of cholelithiasis in mice.     

Conjugated linoleic acid reduces body fat accretion and lipogenic gene expression in neonatal pigs fed low- or high-fat formulas

Childhood obesity is an increasing problem and may predispose children to adult obesity. Weight gain during infancy has been linked to excessive weight later in life. Conjugated linoleic acids (CLA) have been shown to reduce fat gain and body fat mass in animal models and in humans. The effects of CLA in a piglet model of human infancy have not been determined. The objective of this experiment was to examine the regulation of body composition and lipid metabolism in pigs fed low- and high-fat milk formulas supplemented with CLA. Twenty-four piglets were fed low- (3%) or high-fat (25%) diets with or without 1% CLA in a 2 x 2 factorial design. Formulas were fed for 16-17 d. Piglet body weight gains did not differ, although pigs fed the low-fat diets consumed greater amounts of diet. Piglets fed the high-fat formula accreted 50% more body fat during the feeding period than low-fat fed piglets and CLA reduced body fat accretion regardless of dietary fat content. Liver and muscle in vitro oxidation of palmitate was not influenced by dietary treatments. Adipose tissue expression of acetyl-CoA carboxylase-alpha and lipoprotein lipase were significantly reduced by CLA treatment. Overall, CLA reduced body fat accretion without influencing daily gain in a piglet model of human infancy. Results indicate that inhibition of fatty acid uptake and synthesis by adipose tissue, and not increased fatty acid oxidation in liver or muscle, were involved in reducing body fat gain.