QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sisk, M. B. Articles by Azain, M. J. Search for Related Content PubMed PubMed Citation Articles by Sisk, M. B. Articles by Azain, M. J.

---

Articles

Dietary Conjugated Linoleic Acid Reduces Adiposity in Lean but Not Obese Zucker Rats¹

Matthew B. Sisk^*, Dorothy B. Hausman, Roy J. Martin and Michael J. Azain^*2

Departments of ^* Animal and Dairy Science and Foods and Nutrition, University of Georgia, Athens, GA 30602

²To whom correspondence should be addressed. E-mail: mazain{at}arches.uga.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Recent studies have demonstrated a reduction in body fat in growing animals fed conjugated linoleic acid (CLA). Two experiments were conducted to extend these observations to obese rats so that the mechanism of the actions of CLA might be more easily elucidated. In experiment 1, male lean and obese Zucker rats were fed diets containing either 0 or 0.5% CLA for 5 wk. There was no effect of diet on growth rate or food intake. Dietary CLA reduced retroperitoneal and inguinal fat pad weights in the lean rats but increased fat pad weights in the obese genotype (diet x genotype interaction; P < 0.05). Determination of fat pad cellularity indicated that these changes in fat pad weight were due to a reduction or increase in average fat cell size for the lean and obese Zucker rats, respectively. In experiment 2, we sought to reproduce these effects on fat pad size, as well as to determine the effect of dietary CLA on the catabolic response to bacterial endotoxin injection in obese Zucker rats. Growing female lean and obese Zucker rats were fed diets containing 0 or 0.5% CLA for 8 wk. On d 28, each rat was injected intraperitoneally with lipopolysaccharide from Escherichia coli serotype 055:B5 (1 mg/kg body weight) and body weight was determined over the next 96 h. There was a diet x genotype interaction (P < 0.05) for the body weight response to lipopolysaccharide 24 h postinjection. Lean rats fed CLA lost less weight than did lean controls, but obese rats fed CLA lost more weight than did obese controls. As in the first experiment, there was a diet x genotype (P < 0.05) for the effect of treatment on retroperitoneal fat pad weights determined at the end of the experiment. Lean rats fed CLA had smaller RP fat pads than did lean controls, but obese rats fed CLA once again had heavier RP fat pads than did obese controls. These results indicate that CLA reduces body fat and catabolic response to endotoxin injection in lean Zucker rats but not in the obese genotype. The observed interaction between diet and genotype warrants additional investigation into the specific mechanism(s) of the biological activities of CLA.

KEY WORDS: • obese Zucker rats • conjugated linoleic acid • body fat • lipopolysaccharide • antiobesity agent

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Conjugated linoleic acid (CLA)³ is a mixture of positional and geometric isomers of linoleic acid (cis-9, cis-12-octadienoic acid) (1) . In contrast to linoleic acid, which has two cis double bonds at carbons 9 and 12, CLA contains cis and trans isomers at carbons 8 and 10, 9 and 11, 10 and 12 or 11 and 13. There are multiple potential isomers, but the cis-9, trans-11 and trans-10, cis-12 isomers are thought to be active as potential antioxidant, anticarcinogenic, antiobesity and immune-modulating agents (2 ,3) .

The ability of CLA to prevent mammary and other tumors in rodents was first identified in the mid-1980s and has been the subject of several reviews (4 5 6) . There are several reports of interactions of CLA with the immune system. CLA has been shown to enhance T cell function and proliferation and to increase interleukin-2 production, with young animals being more responsive than older animals (7) . Mice fed CLA have an attenuated feed intake response to bacterial endotoxin (8) . The antiobesity effects of CLA were first observed in the mid-1990s.

Numerous studies have demonstrated a reduction in body fat in various species fed diets containing 0.25–2.0% CLA (3 , 9 10 11) . Growing, female Sprague-Dawley rats fed 0.5% CLA for 5–7 wk had 25–30% reductions in the weight of the retroperitoneal and parametrial fat pads that was accounted for by a reduction in cell size rather than cell number (12) .

Although recent articles (6 ,13) have suggested possible mechanisms of action, the basis for the effects of CLA on lipid metabolism, the immune system or tumorigenesis are not yet established.

Typically, investigation into the mechanism by which various factors reduce lipid accretion involves studies of enzyme activity and in vitro metabolism to identify points of control. In the case of the effects of CLA in rats (25–30% reduction in pad weight after 5–7 wk of feeding) (12) , the change in the rate of lipid accretion on a daily basis is likely too small to be detectable in an enzyme activity assay or other in vitro methods. In mice, the effects of CLA are generally of greater magnitude (40–80% reductions in fat mass) (3 ,9 ,11 ,14) than observed in rats, and there is some evidence of enzymatic changes that might account for the observed changes in fat mass.

In vitro, CLA has been shown to inhibit lipoprotein lipase activity and stimulate lipolysis (9) . In mice fed CLA, there is an increase in carnitine palmitoyl transferase activity suggesting an increase in fatty acid oxidation (9) and an increase in metabolic rate (11) . A change in metabolic rate was not as obvious in rats (12) . Because Sprague-Dawley rats are relatively lean and, thus, have low rates of lipid accretion, it was reasoned that the greater rates of lipid accretion in genetically obese Zucker rats (15) might provide a better model to further investigate the mechanism(s) for the effects of dietary CLA on adiposity. Thus, the objective of the present studies was to determine the effect of dietary CLA on fat mass in growing Zucker rats.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Animals and diets.

The protocols for these experiments were approved by the University of Georgia Institutional Animal Care and Use Committee. Two experiments were conducted using lean and obese Zucker rats from the University of Georgia colony. In both experiments, rats were individually housed in hanging wire mesh cages and maintained on a 12-h light-12-h dark cycle at 22 ± 2°C. Rats were acclimated to individual cages and had unlimited access to nonpurified diet (Purina, St. Louis, MO) and water before feeding the test diets. After the adaptation period, experimental diets shown in Table 1 were fed. Feeders that minimized spillage of the powdered diet were used. Diets were based on the AIN-93 recommendations (16) . A purified CLA product (Nu Chek Prep, Elysan, MN) that was 97% CLA, as indicated by the manufacturer, and was found to contain 42.6% of the cis-9/trans-11 isomer, 45.6% of the trans-10/cis-12 isomer and 8.7% of other CLA isomers as determined by gas chromatography was added at the expense of soybean oil and was used in both experiments.

Male lean and obese Zucker rats (7–8 wk old) were randomly assigned to dietary treatment and fed either the control or the 0.5% CLA diet for 5 wk. Representative lean and obese rats (n = 4 per genotype) were processed at the beginning of the study for baseline tissue weights. Body weight and food intake were monitored three times per week. Rats had unlimited access to water, and food was consumed ad libitum from containers designed to minimize spillage. Rats were killed on d 35 by decapitation under carbon dioxide sedation and blood tissue samples were collected. Liver, gastrocnemius muscle and inguinal, retroperitoneal and epididymal fat pads were removed and weighed.

Blood samples were allowed to clot. Serum was obtained by centrifugation (1200 x g for 15 min) and stored at -20°C. Serum samples were analyzed for triglycerides, urea nitrogen, triiodothyronine, thyroxine and insulin using commercially available kits [triglycerides (INT 336), urea nitrogen (BUN 535), Sigma Chemical St. Louis, MO; triiodothyronine, thyroxine and insulin; ICN Pharmaceuticals, Costa Mesa, CA]. Adipose cell size distribution was determined in osmium fixed cells as described previously (17 ,18) . Duplicate 50-mg portions of tissue were fixed in osmium tetroxide. Cell size distribution and number were determined using a Coulter Counter (Coulter Electronics, Hialeah, FL). Cells with diameters from 30 to 240 µm were counted. Additional samples of the retroperitoneal adipose tissue were frozen for later determination of the effect of diet on fatty acid profile.

The fatty acid profile of adipose tissue was determined by gas chromatography using a Shimadzu gas chromatograph (model 14A; Shimadzu Scientific Instruments, Columbia, MD) with a flame ionization detector. Tissue (100 mg) samples were saponified and methylated in duplicate using procedures described previously (12 ,19) . Heptadecanoic acid was used as an internal standard. Fatty acid methyl esters in hexane were separated on a Supelcowax-10 fused silica capillary column (60 m x 0.53 mm, 0.50-µm film thickness; Supelco, Bellefonte, PA) under isothermal conditions. Column temperature was 240°C, injector temperature was 250°C and detector temperature was 260°C. Sample size was 0.5 µL and helium was the carrier gas. Peak identification was based on known standards that included pure samples of cis-9, trans-11 and trans-10, cis-12 CLA (Matreya, Pleasant Gap, PA). Under these conditions, the cis-9, trans-11 (and trans-9, cis-11) isomer elutes after linoleic acid (18:3 9, 12, 15) and is followed by the trans-10, cis-12 isomer (20) .

Experiment 2.

Growing (6-wk-old) female lean and obese Zucker rats were randomly assigned to the control or 0.5% CLA dietary treatments. As in experiment 1, all rats had unlimited access to food and water. Food intake and body weight were recorded two times each week. On d 28, all rats were injected intraperitoneally with 1 mg/kg body weight bacterial endotoxin (lipopolysaccharide [LPS]) from Escherichia coli serotype 055:B5 (Sigma Diagnostics, St. Louis, MO). The objective of this part of the experiment was to determine whether dietary CLA altered the response to endotoxin. Controls were injected with a vehicle (sterile saline). After injection, body weight and feed intake were determined at 24, 48 and 96 h postinjection as a measure of catabolic response. At 4 h postinjection, a blood sample was obtained by tail bleeding. Serum tumor necrosis factor- (TNF-) was determined by enzyme-linked immunosorbant assay (R&D Systems, Minneapolis, MN) as a cytokine measure of catabolic immune response.

At the end of the 8-wk feeding trial, rats were sedated with carbon dioxide and decapitated. Trunk blood was collected for assay, followed by tissue collection for weight determination and assay. Liver, gastrocnemius muscle and inguinal, retroperitoneal and parametrial fat pads were removed and weighed. Blood samples were allowed to clot. Serum was obtained by centrifugation (1200 x g for 15 min) and stored at -20°C. Serum samples were analyzed for triglycerides, free fatty acids, cholesterol and insulin using commercially available kits [triglycerides (INT 336), cholesterol (Total Cholesterol 401), Sigma Chemical, St. Louis, MO; fatty acids (NEFA-C) Wako, Chemical, Dallas, TX; insulin, ICN Pharmaceuticals, Costa Mesa, CA].

Data analysis.

The effects of diet (0 vs 0.5% CLA) and genotype (lean vs. obese) in both experiments were analyzed as a 2 x 2 design with main effects and their interaction included in the model. All results are expressed as least square means. All comparisons between and among means were made with the general linear models procedure of SAS (21) . Data for which variances are unequal were logarithmically transformed before analysis of variance. Untransformed data are shown. Differences were considered significant at P < 0.05.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Experiment 1.

Dietary treatment showed no significant effect on final body weight, average daily gain or average daily feed intake (Table 2 ). Also, efficiency of gain was not affected by diet. The obese genotype was significantly heavier at the end of the experiment and had significantly higher average daily gain and average daily feed intake than did the lean genotype and was significantly more efficient in its feed to gain ratio. Relative to lean rats, obese rats had elevated insulin, triglycerides and urea nitrogen but reduced thyroid hormone levels. There were no significant effects of diet on circulating metabolites or hormones. Dietary CLA significantly reduced the liver weight of both lean and obese rats but had no effect on the weight of the gastrocnemius muscle (Table 2) .

Fatty acid profiles.

Relative to lean rats, obese rats had greater proportions of palmitic, palmitoleic and oleic acids in the retroperitoneal fat (Table 4 ). This is most likely a result of greater rates and contribution of de novo lipogenesis to depot lipid. Dietary CLA significantly increased levels of the cis-9, trans-11 and trans-10, cis-12 isomers of CLA in adipose tissue of both the lean and obese genotypes, but the content expressed as a percentage of total fatty acids was less in obese rats. In both genotypes, CLA feeding decreased the proportions of oleate and linolenate and increased palmitate. There was an interaction of diet and genotype for palmitoleic, with a decrease in lean rats, but an increase in the obese rats fed CLA.

As in experiment 1, obese rats grew at a faster rate and had greater intake than did lean rats. There was no significant effect of CLA on body weight, growth rate or feed intake (Table 5 ). At the midpoint of the feeding trial (d 28), all rats were treated with bacterial endotoxin to determine the influence of diet on the catabolic response to LPS. Body weight decreased in both lean and obese rats (Table 6 ). Obese rats lost more body weight than lean in the first 24 h postinjection. At 24 h postinjection, there was a significant (P < 0.01) diet x genotype interaction. Lean rats fed CLA lost less body weight, whereas obese rats fed CLA lost more weight than did their respective counterparts fed the control diet. Obese rats fed CLA seemed to be more sensitive to the anorectic effects of endotoxin. In the 24 h after LPS injection, there was no difference in intake in lean rats. In the obese rats, intake was less in CLA fed obese rats than in control. Thus, as with gain, there was a diet x genotype interaction for intake. The circulating level of TNF- in blood samples obtained 4 h postinjection was greater in obese rats but was not affected by diet. Body weight gain was positive from 24 to 96 h postinjection. By 96 h, body weights were similar to those preinjection.

Obese rats had higher circulating levels of insulin, triglycerides, fatty acids and cholesterol than did lean rats (Table 5) . There was no effect of diet.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Recent studies have focused on the actions of CLA as a metabolic mediator of fat deposition and catabolic modulator of the immune response (9 ,22) . CLA has been shown to increase growth rates and efficiency of gain in rats (23) , mice (11) and swine (24) , while altering the partitioning of nutrients from fat to lean tissue (9) . CLA attenuated the response to LPS in mice (22) . However, the number of studies focusing on Zucker rats or other such animal models of obesity has been very limited. Houseknecht et al. (25) reported that dietary CLA improved glucose tolerance in Zucker diabetic fatty rats, a substrain that differs from those used in the present work. The present study has yielded results that cast doubt on the universality of the benefits of CLA as far as fat deposition reduction and lean tissue repartitioning.

The exact mechanism(s) by which CLA exerts its various metabolic effects remain unclear (13) . It is not known whether the pathways by which CLA reduces fat, inhibits carcinogenesis and reduces immune response are separate or share a common mechanism. Recent studies have demonstrated that the cis-10, trans-12 isomer of CLA is most likely responsible for reducing body fat (3 ,26) . In the present study, lean Zucker rats fed CLA showed responses similar to those of Sprague-Dawley rats (12) , mice (9 ,11 ,14) and pigs (10 ,24) as related to fat deposition. The weight of the retroperitoneal pad was reduced in both male (-24%; Table 3 ) and female lean Zucker rats (-25%; Table 5 ). This is very similar to the reductions reported in female Sprague-Dawley rats (12) . The same is not true of obese Zucker rats. In fact, CLA had the opposite effect in the obese genotype of Zucker rats, increasing fat deposition.

Significant interactions of diet (0 vs 0.5% CLA) and genotype (lean vs. obese) were seen for fat pad weight in separate experiments with male (Experiment 1) and female rats (Experiment 2), as well as with independent endpoints (fat pad weight and cell size distribution). In addition, there was a diet x genotype interaction for the anorectic response to LPS (Table 6) . Previous studies have shown that mice fed CLA at levels of 0.5% in the diet have attenuated responses to the anorectic effects of endotoxin administration (8 ,24) , especially weight loss. This was observed in the lean rats fed CLA, but an increased sensitivity to LPS was noted in obese rats fed CLA.

The specific mechanism by which CLA exerts these effects remains unknown, but several hypotheses have been offered, including inhibition of arachidonic acid formation (27) and modulation of desaturase activity in the liver (28) . Obese rats have numerous metabolic abnormalities associated with lipid metabolism. These include increased lipid accretion (15) , reduced desaturase activity (29) accompanied by reduced arachidonate tissue concentrations (30) and adipocyte hyperplasia and hypertrophy (31) . However, none of these alterations would be expected to result in opposite responses to dietary CLA. If anything, a change in the magnitude of the response but not a change in direction would be expected. For example, tissue levels of CLA were lower in the obese than in the lean rats. This is most likely accounted for by dilution of the fatty acid into a larger pad. On a per pad basis, the absolute amount of CLA was actually greater in obese rats vs lean (88.6 vs 26.4 mg; P < 0.01). This is likely a factor of increased intake and differences in turnover.

CLA has been shown to normalize impaired glucose tolerance in diabetic fatty Zucker rats (25) . The Zucker rats used in the present studies are not overtly diabetic. However, they do exhibit insulin resistance. Feeding CLA caused a numerical reduction (P = 0.13) in insulin levels in male obese rats (Table 2) , but had no effect on females (Table 5) or on the lean genotype. Based on our current understanding of the actions of CLA and of genetically obese rats, we suggest that the means by which CLA decreases fat in lean rats but increases fat in obese rats may be due to a normalized glucose tolerance paired with the hyperphagia of obese animals, resulting in more glucose availability as a substrate for an enlarged fat mass.

Disparate actions of CLA have been noted in relation to the immune response and age, with mature animals mounting more complete immune responses than neonates or old animals, due mainly to a lack of immune system maturity and senescence of primary lymphoid organs, respectively (7) . In the present study, at 24 h post LPS injection, there was a significant interaction between genotype and diet, with lean rats fed CLA showing reduced weight loss while obese rats fed CLA showed increased weight loss due to the endotoxin injection. A similar reduced sensitivity to LPS has been noted previously in obese Zucker rats (32) . To further inquire into the means by which the interaction of diet and genotype was occurring, plasma levels of TNF- were determined, but yielded no significant effects of CLA. Elevated TNF- in obese rats has been observed previously (33) . CLA has been reported to reduce macrophage cytokine production (34) , and TNF- is one of the principle cytokines mediating the immune response to LPS in mammals (35 ,36) . However, recent articles on the subject have reported that CLA may be acting through a non-TNF- cytokine in its reduction of the immune response (37) , possibly by reducing prostaglandin biosynthesis (38 ,39) . As stated earlier, numerous benefits related to inclusion of CLA in the diet have been suggested. In particular, the antiobesity effects of CLA have received much attention. The results of the present study suggest that although CLA reduces fat pad weight in growing lean rats, it did not have an effect on rats in which the obesity is already established. Thus, the use of CLA as a treatment for obesity can be questioned. Use of CLA in adult humans has had mixed results. In a recent study (40) , adults fed CLA for 12 wk had reduced fat mass and increased lean mass. In other work (41) , no significant effect of dietary CLA on fat mass was observed. Despite the lack of effect of CLA in some studies, it may, however, have potential as a preventative agent. Furthermore, the present results also suggest that CLA may increase fat deposition and sensitivity to endotoxin in obese animals. Studies to definitively establish the basis for the disparate responses in fat deposition and immune response in lean and obese Zucker rats are warranted to explain why this phenomenon is occurring. Thus, the present results are indicative of the possible pitfalls of assuming universality of action for any nutrient and the necessity of establishing a mechanistic basis for any nutrient’s in vivo actions.

	FOOTNOTES

 
¹ Presented in part at the Experimental Biology Meeting 99, April 1999, Washington, D.C. by [Sisk, M. & Azain, M. J.(1999)Effect of conjugated linoleic acid on fat pad weights and catabolic response to endotoxin injection in lean and obese Zucker rats. FASEB J. 13: A859].

³ Abbreviations used: CLA, conjugated linoleic acid; LPS, lipopolysaccharide; TNF-, tumor necrosis factor-.

Manuscript received October 27, 2000. Initial review completed December 21, 2000. Revision accepted March 8, 2001.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 

1. Garcia H. S., Storkson J. M., Pariza M. W., Hill C. G. Enrichment of butteroil with conjugated linoleic acid via enzymatic interesterification. Biotech. Lett. 1998;20:393-395

2. Lin H., Boylston T. D., Chang M. J., Luedecke L. O., Shultz T. D. Survey of the conjugated linoleic acid contents of dairy products. J. Dairy Sci. 1995;78:2358-2365[Abstract]

3. Park Y., Storkson J. M., Albright K. J., Lie W., Pariza M. W. Evidence that the trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 1999;34:235-241[Medline]

4. Ip C., Singh M., Thompson H. J., Scimeca J. A. Conjugated linoleic acid suppresses mammary carcinogenesis and proliferative activity of the mammary gland in the rat. Cancer Res 1994;54:1212-1215[Abstract/Free Full Text]

5. Scimeca J. A., Thompson H. J., Ip C. Effect of conjugated linoleic acid on carcinogenesis. Adv. Exp. Med. Biol. 1994;364:59-65[Medline]

6. Belury M. A. Conjugated dienoic linoleate: a polyunsaturated fatty acid with unique chemoprotective properties. Nutr. Rev. 1995;53:83-89[Medline]

7. Hayek M. G., Han S. N., Wu D., Watkins B. A., Meydani M., Dorsey J. L., Smith D. E., Meydani S. N. Dietary conjugated linoleic acid influences the immune response of young and old C57BL/6NCrlBR mice. J. Nutr. 1999;129:32-38[Abstract/Free Full Text]

8. Cook M. E., Miller C. C., Park Y., Pariza M. Immune modulation by altered nutrient metabolism: nutritional control of immune-induced growth depression. Poult. Sci. 1993;72:1301-1305[Medline]

9. Park Y., Albright K. J., Liu W., Storkson J. M., Cook M. E., Pariza M. W. Effect of conjugated linoleic acid on body composition in mice. Lipids 1997;32:853-858[Medline]

10. Ostrowska E., Muralitharan M., Cross R. F., Bauman D. E., Dunshea F. R. Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs. J. Nutr. 1999;129:2037-2042[Abstract/Free Full Text]

11. West D. B., Delany J. P., Camet P. M., Blohm F., Truett A. A., Scimeca J.. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am. J. Physiol. 1998;44:R667-R672

12. Azain M. J., Hausman D. B., Sisk M. B., Flatt W. P., Jewell D. E. Dietary conjugated linoleic acid reduces rat adipose tissue cell size rather than cell number. J. Nutr. 2000;130:1548-1554[Abstract/Free Full Text]

13. Pariza M. W., Park Y., Cook M. E. Mechanisms of action of conjugated linoleic acid: evidence and speculation. Proc. Soc. Exp. Biol. Med. 2000;223:8-13[Abstract/Free Full Text]

14. DeLany J. P., Blohm F., Truett A. A., Scimeca J. A., West D. B.. Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Am. J. Physiol. 1999;276:R1172-R1179

15. Azain M. J., Hausman D. B., Kasser T. R., Martin R. J. Effect of somatotropin and feed restriction on body composition and adipose tissue metabolism in obese Zucker rats. Am. J. Physiol. 1995;269:E137-E144[Abstract/Free Full Text]

16. Reeves P. G., Nielsen R. H., Fahey G. C., Jr AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J. Nutr. 1993;123:1939-1951

17. Lee K. C., Azain M. J., Hardin M. A., Williams S. E. Effect of porcine somatotropin (pST) treatment and withdrawal on performance and adipose tissue cellularity in finishing swine. J. Anim. Sci. 1994;72:1702-1711[Abstract]

18. Mersmann H. J., MacNeil M. D. Variables in estimation of adipocyte size and number with a particle counter. J. Anim. Sci. 1986;62:980-986

19. Azain M. J. Effects of adding medium chain triglycerides to sow diets during late gestation and early lactation on litter performance. J. Anim. Sci. 1993;71:3011-3019[Abstract]

20. Ha Y. L., Grimm N. K., Pariza M. W. Newly recognized anticarcinogenic fatty acids: identification and quantification in natural and processed cheeses. J. Agric. Food Chem. 1989;37:75-81

21. SAS Institute, Inc SAS Users Guide: Statistics 1985 SAS Institute, Inc Cary, NC.

22. Miller C. C., Park Y., Pariza M. W., Cook M. E. Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection. Biochem. Biophys. Res. Commun. 1994;198:1107-1112[Medline]

23. Chin S. F., Storkson J. M., Albright K. J., Cook M. E., Pariza M. Conjugated linoleic acid is a growth factor for rats as shown by enhanced weight gain and improved feed efficiency. J. Nutr. 1994;124:2344-2349

24. Dugan M. E. R., Aalhus J. L., Schaefer A. L., Kramer J. K. G. The effect of conjugated linoleic acid on fat to lean repartitioning and feed conversion in pigs. Can. J. Anim. Sci. 1997;77:723-725

25. Houseknecht K. L., Vanden Heuvel J. P., Moya-Camarena S. Y., Portocarrero C. P., Peck L. W., Nickel K. P., Belury M. A. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem. Biophys. Res. Commun. 1998;244:678-682[Medline]

26. Choi Y., Kim Y.-C., Han Y.-B., Park Y., Pariza M. W., Ntambi J. M. The trans-10, cis-12 isomer of conjugated linoleic acid downregulates steroyl-CoA desaturase 1 gene expression in 3T3–L1 adipocytes. J. Nutr. 2000;130:1920-1924[Abstract/Free Full Text]

27. Parker J., Daniel L. W., Waite M. Evidence of protein kinase C involvement in phorbol diester-stimulated arachidonic acid release and prostaglandin synthesis. J. Biol. Chem. 1987;262:5383-5393

28. Lee K. N., Pariza M. W., Ntambi J. M. Conjugated linoleic acid decreases hepatic stearoyl-CoA desaturase mRNA expression. Biochem. Biophys. Res. Commun. 1998;248:817-821[Medline]

29. Blond J.-P., Henrhiri C., Bezard J. -6 and -5 desaturase activities in liver from obese Zucker rats at different ages. Lipids 1989;24:389-395[Medline]

30. Ayre K. J., Phinney S. D., Tanna A. B., Stern J. S. Exercise training reduces skeletal muscle membrane arachidonates in the obese (fa/fa) Zucker rat. J. Appl. Physiol. 1998;85:1898-1902[Abstract/Free Full Text]

31. Marques B. G., Hausman D. B., Martin R. J. Association of fat cell size and paracrine growth factors in development of hyperplastic obesity. Am. J. Physiol. 1998;:R1898-R1908

32. Rosenthal M., Roth J., Storr B., Zeisberger E. Fever response in lean (Fa/-) and obese (fa/fa) Zucker rats and its lack to repeated injections of LPS. Physiol. Behav. 1996;59:787-793[Medline]

33. Hotsamisligil G. S., Spiegelman B. M. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 1994;43:1271-1278[Abstract]

34. Turek J. J., Li Y., Schoenlein I. A., Allen K. G. D., Watkins B. A. Modulation of macrophage cytokine production by conjugated linoleic acids is influenced by the dietary n-6:n-3 fatty acid ratio. J. Nutr. Biochem. 1998;9:258-266

35. Schletter J., Heine H., Ulmer A. J., Rietschel E. T. Molecular mechanisms of endotoxin activity. Arch. Microbiol. 1995;164:383-389[Medline]

36. Tolchard S., Hare A. S., Nutt D. J., Clarke G. TNF- mimics the endocrine but not the thermoregulatory responses of bacterial lipopolysaccharide (LPS): correlation with FOS-expression in the brain. Neuropharmacology 1996;35:243-248[Medline]

37. Sugano M., Tsujita A., Yamasaki M., Noguchi M., Yamada K. Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats. Lipids 1998;33:521-527[Medline]

38. Li Y., Watkins B. A. Conjugated linoleic acids alter bone fatty acid composition and reduce ex vivo prostaglandin E2 biosynthesis in rats fed n-6 or n-3 fatty acids. Lipids 1998;33:417-425[Medline]

39. Hamberg M. Stereochemistry of oxygenation of linoleic acid catalyzed by prostaglandin-endoperoxide H synthase-2. Arch. Biochem. Biophys. 1998;349:376-380[Medline]

40. Blankson H., Stakkestad J. A., Fagertun H., Thom E., Wadsteinn J., Gudmundsen O. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J. Nutr. 2000;130:2943-2948[Abstract/Free Full Text]

41. Zambell K. L., Klein N. L., Van Loan M. D., Gale B., Benito P., Kelley D. S., Nelson G. J. Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Lipids 2000;35:777-782[Medline]

This article has been cited by other articles:

				R. N Close, D. A Schoeller, A. C Watras, and E. H Nora Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep Am. J. Clinical Nutrition, September 1, 2007; 86(3): 797 - 804. [Abstract] [Full Text] [PDF]

				R. J. Wynn, Z. C. T. R. Daniel, C. L. Flux, J. Craigon, A. M. Salter, and P. J. Buttery Effect of feeding rumen-protected conjugated linoleic acid on carcass characteristics and fatty acid composition of sheep tissues J Anim Sci, December 1, 2006; 84(12): 3440 - 3450. [Abstract] [Full Text] [PDF]

				L. Badinga and E. S. Greene Physiological Properties of Conjugated Linoleic Acid and Implications for Human Health Nutr Clin Pract, August 1, 2006; 21(4): 367 - 373. [Abstract] [Full Text] [PDF]

				C. Corino, A. Di Giancamillo, R. Rossi, and C. Domeneghini Dietary Conjugated Linoleic Acid Affects Morphofunctional and Chemical Aspects of Subcutaneous Adipose Tissue in Heavy Pigs J. Nutr., June 1, 2005; 135(6): 1444 - 1450. [Abstract] [Full Text] [PDF]

				P. P. Mirand, M.-A. Arnal-Bagnard, L. Mosoni, Y. Faulconnier, J.-M. Chardigny, and Y. Chilliard Cis-9, Trans-11 and Trans-10, Cis-12 Conjugated Linoleic Acid Isomers Do Not Modify Body Composition in Adult Sedentary or Exercised Rats J. Nutr., September 1, 2004; 134(9): 2263 - 2269. [Abstract] [Full Text] [PDF]

				Y. Wang and P. J. Jones Dietary conjugated linoleic acid and body composition Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1153S - 1158S. [Abstract] [Full Text] [PDF]

				V. Bontempo, D. Sciannimanico, G. Pastorelli, R. Rossi, F. Rosi, and C. Corino Dietary Conjugated Linoleic Acid Positively Affects Immunologic Variables in Lactating Sows and Piglets J. Nutr., April 1, 2004; 134(4): 817 - 824. [Abstract] [Full Text] [PDF]

				M. A. Belury, A. Mahon, and S. Banni The Conjugated Linoleic Acid (CLA) Isomer, t10c12-CLA, Is Inversely Associated with Changes in Body Weight and Serum Leptin in Subjects with Type 2 Diabetes Mellitus J. Nutr., January 1, 2003; 133(1): 257S - 260. [Abstract] [Full Text] [PDF]

				M. A. Belury Inhibition of Carcinogenesis by Conjugated Linoleic Acid: Potential Mechanisms of Action J. Nutr., October 1, 2002; 132(10): 2995 - 2998. [Abstract] [Full Text] [PDF]

				J.-C. Bouthegourd, P. C. Even, D. Gripois, B. Tiffon, M.-F. Blouquit, S. Roseau, C. Lutton, D. Tome, and J.-C. Martin A CLA Mixture Prevents Body Triglyceride Accumulation without Affecting Energy Expenditure in Syrian Hamsters J. Nutr., September 1, 2002; 132(9): 2682 - 2689. [Abstract] [Full Text] [PDF]

				S. B. Smith, T. S. Hively, G. M. Cortese, J. J. Han, K. Y. Chung, P. Castenada, C. D. Gilbert, V. L. Adams, and H. J. Mersmann Conjugated linoleic acid depresses the {delta}9 desaturase index and stearoyl coenzyme A desaturase enzyme activity in porcine subcutaneous adipose tissue J Anim Sci, August 1, 2002; 80(8): 2110 - 2115. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sisk, M. B. Articles by Azain, M. J. Search for Related Content PubMed PubMed Citation Articles by Sisk, M. B. Articles by Azain, M. J.