In Utero Exposure to trans-10, cis-12 Conjugated Linoleic Acid Modifies Postnatal Development of the Mammary Gland and its Hormone Responsiveness.

We previously showed that dietary trans-10, cis-12 conjugated linoleic acid (10,12 CLA) stimulates estrogen-independent mammary growth in young ovariectomized mice. Here we investigated the effects of in utero or postnatal exposure to cis-9, trans-11 (9,11 CLA) and 10,12 CLA on postnatal development of the mammary gland and its responsiveness to ovarian steroids. In the first experiment we fed dams different CLA prior to and during gestation, then cross fostered female pups onto control fed dams prior to assessing the histomorphology of their mammary glands. Pregnant dams in the second experiment were similarly exposed to CLA, after which their female pups were ovariectomized then treated with 17ß-estradiol (E), progesterone (P) or E + P for 5 days. In a third experiment, mature female mice were fed different CLA for 28 days prior to ovariectomy, then treated with E, P or E + P. Our data indicate that 10,12 CLA modifies the responsiveness of the mammary glands to E or E + P when exposure occurs either in utero, or postnatally. These findings underline the sensitivity of the mammary glands to dietary fatty acids and reinforce the potential for maternal nutrition to impact postnatal development of the mammary glands and their risk for developing cancer.

Conjugated linoleic acid supplements preserve muscle in high-body-fat adults: A double-blind, randomized, placebo trial.

BACKGROUND AND AIMS: Conjugated linoleic acid (CLA) has been used to improve body composition in weight management. However, clinical trial results are inconsistent and limited among Asians. We aimed to investigate the effect of CLA on body composition of Chinese adults with elevated body fat percentage. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial, 66 Chinese adults (aged 18-45 years old, 37.9% male) with elevated body fat percentage were provided with 3.2 g/day CLA (n = 33) or 3.2 g/day placebo (sunflower oil; n = 33) for 12 weeks. Both groups received lifestyle counseling, featured with low fat and low sugar diet, and moderate physical activity. Body composition was measured using dual-energy X-ray absorptiometry at the baseline and end of the trial. Sixty-four participants finished this study. Compared with the placebo group, the CLA group showed increased trunk muscle mass (MM) (0.6 ± 1.7 vs. -0.3 ± 1.2 kg, P = 0.019). Among those with an adherence score higher than 0.80 (n = 56, 87.5%), a greater increase in both total and trunk MM was observed in the CLA group (both P < 0.05). Moreover, the effect on MM appeared to be more evident in men, those with a body mass index <25 kg/m2, or those with higher self-rated physical activity. CONCLUSIONS: In Chinese adults with elevated body fat percentage, 3.2 g/day CLA supplementation may be effective in preserving MM, especially in the trunk region. REGISTRATION: This study was registered at ClinicalTrials.gov as NCT03915808 on April 9, 2019.

Ácidos grasos trans y ácido linoleico conjugado en alimentos: origen y propiedades biológicas / Trans fatty acids and conjugated linoleic acid in food: origin and biological properties

Los ácidos grasos trans (AGT) son componentes lipídicos minoritarios que se encuentran en distintos alimentos, entre ellos, aquellos derivados de animales rumiantes, que han merecido atención por su relación con el riesgo de incidir en enfermedades cardiovasculares. El origen de los AGT en los alimentos se encuentra mayoritariamente en los procesos de hidrogenación industrial de aceites vegetales insaturados y en las reacciones enzimáticas de biohidrogenación que tienen lugar, de forma natural, en el tracto digestivo de los rumiantes. Aunque las moléculas que se generan por ambos mecanismos son similares, la distribución isomérica de los AGT es muy diferente, lo que puede generar diferencias a la hora de evaluar los efectos biológicos derivados de su consumo. Las grasas vegetales hidrogenadas son abundantes en ácido elaídico (trans-9 18:1) y trans-10 18:1 entre otros. En contraste, el ácido vacénico (trans-11 18:1) es el principal AGT presente en la leche y otros productos derivados de rumiantes, siendo además precursor fisiológico del ácido linoleico conjugado, un componente al que se atribuyen numerosos efectos beneficiosos para la salud. En este artículo se actualizan los efectos biológicos y las potenciales propiedades bioactivas de estos ácidos grasos

Trans fatty acids (TFA) are minor lipid components present in different foods, including ruminant derived products, which have received great attention due to their relationship with cardiovascular disease risk. The origin of TFA in food is mainly related to the industrial hydrogenation processes of unsaturated vegetable oils, but they can also occur naturally in the digestive tract of ruminants by enzymatic biohydrogenation reactions. Both mechanisms generate similar TFA compounds. However, TFA consumption may exert different biological effects depending on the isomeric distribution, which is strongly influenced by the dietary source (i.e., industrial or natural). Industrial partially hydrogenated vegetable fats are rich in elaidic (trans-9 18:1) and trans-10 18:1 fatty acids, among others. In contrast, vaccenic acid (trans-11 18:1) is the major TFA isomer detected in milk and other ruminant derived products. Vaccenic acid is the physiological precursor of conjugated linoleic acid, a bioactive lipid with beneficial effects on human health. This article provides updated information on the biological effects and potential bioactive properties of TFA considering both, their chemical structure and provenance

Conjugated linoleic acid (CLA)-induced milk fat depression: application of RNA-Seq technology to elucidate mammary gene regulation in dairy ewes.

Milk fat depression (MFD) is characterized by a reduction in the content of milk fat, presumably caused by the anti-lipogenic effects of rumen biohydrogenation intermediates, such as trans-10 cis-12 conjugated linoleic acid (CLA). In this study, RNA-Seq technology was used to help elucidate the mammary responses involved in CLA-induced MFD in lactating ewes. To this end, we compared the milk somatic cell transcriptome of ewes suffering from CLA-induced MFD with control ewes (i.e., those without MFD), as well as with ewes fed a diet supplemented with fish oil (FO-MFD) that we previously reported affects the mammary transcriptome. In the differential expression analysis between CLA-MFD and controls, we identified 1,524 differentially expressed genes (DEGs), whereas 653 were detected between CLA- and FO-MFD groups. Although this article focuses on lipid metabolism, CLA affected the expression of many genes related to other biological processes, especially immunity. Among the 55 genes shared by both MFD conditions, some genes linked to fatty acid synthesis, such as ACACA, AACS, ACSS2, or ACSS3, were downregulated. In addition, this study provides a list of candidate genes that are not usually considered in the nutrigenomics of MFD but that may act as key regulators of this syndrome in dairy ewes.

[Trans fatty acids and conjugated linoleic acid in food: origin and biological properties]. / Ácidos grasos trans y ácido linoleico conjugado en alimentos: origen y propiedades biológicas.

INTRODUCTION: Trans fatty acids (TFA) are minor lipid components present in different foods, including ruminant derived products, which have received great attention due to their relationship with cardiovascular disease risk. The origin of TFA in food is mainly related to the industrial hydrogenation processes of unsaturated vegetable oils, but they can also occur naturally in the digestive tract of ruminants by enzymatic biohydrogenation reactions. Both mechanisms generate similar TFA compounds. However, TFA consumption may exert different biological effects depending on the isomeric distribution, which is strongly influenced by the dietary source (i.e., industrial or natural). Industrial hydrogenated vegetable fats are rich in elaidic (trans-9 18:1) and trans-10 18:1 fatty acids, among others. In contrast, vaccenic acid (trans-11 18:1) is the major TFA isomer detected in milk and other ruminant derived products. Vaccenic acid is the physiological precursor of conjugated linoleic acid, a bioactive lipid with beneficial effects on human health. This article provides updated information on the biological effects and potential bioactive properties of TFA considering both, their chemical structure and provenance.

INTRODUCCIÓN: Los ácidos grasos trans (AGT) son componentes lipídicos minoritarios que se encuentran en distintos alimentos, entre ellos, aquellos derivados de animales rumiantes, que han merecido atención por su relación con el riesgo de incidir en enfermedades cardiovasculares. El origen de los AGT en los alimentos se encuentra mayoritariamente en los procesos de hidrogenación industrial de aceites vegetales insaturados y en las reacciones enzimáticas de biohidrogenación que tienen lugar, de forma natural, en el tracto digestivo de los rumiantes. Aunque las moléculas que se generan por ambos mecanismos son similares, la distribución isomérica de los AGT es muy diferente, lo que puede generar diferencias a la hora de evaluar los efectos biológicos derivados de su consumo. Las grasas vegetales hidrogenadas son abundantes en ácido elaídico (trans-9 18:1) y trans-10 18:1 entre otros. En contraste, el ácido vacénico (trans-11 18:1) es el principal AGT presente en la leche y otros productos derivados de rumiantes, siendo además precursor fisiológico del ácido linoleico conjugado, un componente al que se atribuyen numerosos efectos beneficiosos para la salud. En este artículo se actualizan los efectos biológicos y las potenciales propiedades bioactivas de estos ácidos grasos.

Tissue-dependent effects of cis-9,trans-11- and trans-10,cis-12-CLA isomers on glucose and lipid metabolism in adult male mice.

Mixtures of the two major conjugated linoleic acid (CLA) isomers trans-10,cis-12-CLA and cis-9,trans-11-CLA are used as over the counter supplements for weight loss. Because of the reported adverse effects of CLA on insulin sensitivity in some mouse studies, we sought to compare the impact of dietary t10c12-CLA and c9t11-CLA on liver, adipose tissue, and systemic metabolism of adult lean mice. We fed 8 week-old C57Bl/6J male mice with low fat diets (10.5% Kcal from fat) containing 0.8% t10c12-CLA or c9t11-CLA for 9 or 38 days. Diets containing c9t11-CLA had minimal impact on the endpoints studied. However, 7 days after starting the t10c12-CLA diet, we observed a dramatic reduction in fat mass measured by NMR spectroscopy, which interestingly rebounded by 38 days. This rebound was apparently due to a massive accumulation of lipids in the liver, because adipose tissue depots were visually undetectable. Hepatic steatosis and the disappearance of adipose tissue after t10c12-CLA feeding was associated with elevated plasma insulin levels and insulin resistance, compared to mice fed a control diet or c9t11-CLA diet. Unexpectedly, despite being insulin resistant, mice fed t10c12-CLA had normal levels of blood glucose, without signs of impaired glucose clearance. Hepatic gene expression and fatty acid composition suggested enhanced hepatic de novo lipogenesis without an increase in expression of gluconeogenic genes. These data indicate that dietary t10c12-CLA may alter hepatic glucose and lipid metabolism indirectly, in response to the loss of adipose tissue in mice fed a low fat diet.

Liver lipid metabolism disruption in cancer cachexia is aggravated by cla supplementation -induced inflammation.

BACKGROUND & AIMS: The liver is the main organ regulating metabolism. In spite of that, few studies examine liver metabolism in cachexia, a wasting syndrome associated with increased morbidity and mortality in cancer. Cachexia induces major metabolic disruption, inflammation and fat and lean mass loss. We have previously shown impairment of hepatic lipid metabolism in cancer cachexia that contributes to the aggravation of the symptoms. The present study addresses the effects of Conjugated Linoleic Acid supplementation upon liver lipid metabolism in cachectic rats. METHODS: Male Wistar rats were randomly assigned to control groups (C) receiving 0.9 NaCl (Placebo CP); or to groups supplemented with sunflower oil (CSF), supplemented with CLA (CCLA), or still, to tumour bearing animals (T) receiving NaCl (TP), sunflower oil (TSF), or CLA (TCLA). Supplementation (0.5 ml) by gavage was carried out for 14 days. Body weight, dietary intake, glucose, cholesterol and triacylglycerol plasma content, liver glycogen and triacylglycerol content and mRNA expression of liver carnitine palmitoyltransferase I and II (CPT I and II), as well as microsomal triglyceride transfer protein (MTP), liver fatty acid-binding protein (L-FABP), peroxisome proliferator-activated receptor-alpha (PPAR-alpha), and apolipoprotein B (apoB), were assessed. RESULTS: Liver CPT II activity was reduced in all groups, when compared with CP. Hepatic mRNA expression of MTP, apoB and FABP was reduced in TCLA, when compared with all groups. TCLA also presented increased hepatic and plasma triacylglycerol content, when compared with all T groups. Adipose tissue-derived inflammatory factors were assessed. No differences among the groups were observed in regard to Retro Peritoneal Adipose Tissue cytokine (IL-1ß, IL-6, and TNF-α) protein content and expression, with the exception of IL-10 in tumour-bearing animals. In the Epididymal Adipose Tissue, the inflammatory cytokines were augmented in TCLA, compared with all other groups. CONCLUSION: CLA supplementation fails to promote the re-establishment of hepatic lipid metabolism in tumour-bearing animals, and therefore is not recommended in cancer-related cachexia.

The effect of conjugated linoleic acid on oxidative stress and matrix metalloproteinases 2 and 9 in patients with COPD.

Background: Natural antioxidants in foods may be used in prevention and treatment of oxidative stress and inflammation in COPD. Therefore, this study aimed to evaluate the effect of conjugated linoleic acid (CLA) supplement as natural antioxidants on oxidative stress levels, and MMP2 and MMP9 serum levels in COPD patients. Materials and methods: This clinical trial study was conducted on 90 (supplement group=45 and control group=45) COPD patients in Ardabil city, Iran, in 2015. After obtaining written consent, general information was collected from each patient using a validated and reliable questionnaire. Supplement group received 3.2 g of CLA and those in the control group were given 3.2 g of placebo for 6 weeks on a daily basis. Fasting blood samples were taken from all of the patients for testing of malondialdehyde (MDA), MMP2, and MMP9 levels at the beginning and end of the study. Data were analyzed using Kolmogorov-Smirnov test, independent samples t-test, paired sample t-test, chi-square test, and ANOVA. Results: There were no significant differences between the two groups with regard to mean age, smoking status, and serum level of MDA at the beginning of the study. In the supplement group, the serum level of MDA decreased significantly at the end of the 6th week compared to that in the beginning of the study (p=0.0004), while in the placebo group, the difference was found to be insignificant. The serum level of MMP9 decreased significantly in the supplement group, while in the placebo group its level increased significantly as compared to that at the beginning of the study (p<0.05). The serum levels of MMP2 indicated no significant differences between the two groups neither at the beginning nor at the end of the study. Conclusion: These findings indicated that CLA supplementation may be helpful for COPD patients through inhibiting the production of oxidative stress and controlling MMP9 serum levels.

Consumption of conjugated linoleic acid (CLA)-supplemented diet during colitis development ameliorates gut inflammation without causing steatosis in mice.

Dietary supplementation with conjugated linoleic acid (CLA) has been proposed for weight management and to prevent gut inflammation. However, some animal studies suggest that supplementation with CLA leads to the development of nonalcoholic fatty liver disease. The aims of this study were to test the efficiency of CLA in preventing dextran sulfate sodium (DSS)-induced colitis, to analyze the effects of CLA in the liver function, and to access putative liver alterations upon CLA supplementation during colitis. So, C57BL/6 mice were supplemented for 3 weeks with either control diet (AIN-G) or 1% CLA-supplemented diet. CLA content in the diet and in the liver of mice fed CLA containing diet were accessed by gas chromatography. On the first day of the third week of dietary treatment, mice received ad libitum a 1.5%-2.5% DSS solution for 7 days. Disease activity index score was evaluated; colon and liver samples were stained by hematoxylin and eosin for histopathology analysis and lamina propria cells were extracted to access the profile of innate cell infiltrate. Metabolic alterations before and after colitis induction were accessed by an open calorimetric circuit. Serum glucose, cholesterol, triglycerides and alanine aminotransaminase were measured; the content of fat in liver and feces was also accessed. CLA prevented weight loss, histopathologic and macroscopic signs of colitis, and inflammatory infiltration. Mice fed CLA-supplemented without colitis induction diet developed steatosis, which was prevented in mice with colitis probably due to the higher lipid consumption as energy during gut inflammation. This result suggests that CLA is safe for use during gut inflammation but not at steady-state conditions.

Co-administration of conjugated linoleic acid and rosiglitazone increases atherogenic co-efficient and alters isoprenaline-induced vasodilatation in rats fed high fat diet.

The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (R(max)=53+/-4.7 %; pEC50=6+/-0.2) compared to endothelium-intact aortas (R(max)=100+/-9.9 %; pEC50=7+/-0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endothelium-independent vasodilatation before the onset of HFD-induced insulin resistance.

Effect of conjugated linoleic acid on blood inflammatory markers: a systematic review and meta-analysis on randomized controlled trials.

BACKGROUND/OBJECTIVES: Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid with attractive biological activities. Numerous studies have been conducted on the inflammation-lowering effects of CLA in in vitro and animal models. However, the effects of CLA treatment on the inflammatory markers in humans are controversial. Therefore, the objective of this study was to perform a systematic review and meta-analysis on controlled clinical trials (RCT) assessing the effects of CLA supplementation on the circulating inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). SUBJECTS/METHODS: The literature search of RCTs was performed using Pubmed/Medline, Scopus, ScienceDirect, Web of science, Cochrane, and Google Scholar databases from inception to March 2017. Weighted mean differences were estimated and the pooled effect size was calculated by a random effects model. RESULTS: Of the 427 identified studies, eleven RCTs, including 420 subjects were included in the statistical analysis. Findings suggested that CLA supplementation increased blood levels of CRP by 0.89 mg/l (95% CI: 0.11, 1.68; P = 0.025) and TNF-α levels by 0.39 pg/ml (95% CI: 0.23, 0.55; P < 0.0001). However, blood IL-6 levels were marginally decreased by 0.32 pg/ml (95% CI: -0.71, 0.07; P = 0.11) following CLA supplementation. There was a significant heterogeneity for the impact of CLA on CRP and IL-6, but not TNF-α. CONCLUSIONS: This meta-analysis showed that CLA supplementation may increase inflammatory markers (CRP and TNF-α). There are concerns about using CLA supplementation as an anti-obesity agent among the obese population for at least a short duration.

Trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) treatment and caloric restriction differentially affect adipocyte cell turnover in obese and lean mice.

Caloric restriction (CR) is one of the most promising strategies for weight loss but is associated with loss of lean mass, whereas compounds such as trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) have been promoted as antiobesity agents. To compare the mechanisms of weight reduction by CR and t10-c12 CLA, body composition, glucose control, and characteristics of adipose tissue with respect to cell turnover (stem cells and preadipocytes, apoptosis and autophagy) and Tbx-1 localization were examined in obese db/db mice and lean C57BL/6J mice undergoing CR or fed CLA isomers (0.4% w/w c9-t11 or t10-c12) for 4 weeks. Our findings show that the t10-c12 CLA reduced whole-body fat mass by decreasing all fat depots (visceral, inguinal, brown/interscapular), while CR lowered both whole-body fat and lean mass in obese mice. t10-c12 CLA elevated blood glucose in both obese and lean mice, while glycemia was not altered by CR. The adipocyte stem cell population remained unchanged; however, t10-c12 CLA reduced and CR elevated the proportion of immature adipocytes in obese mice, suggesting differential effects on adipocyte maturation. t10-c12 CLA reduced apoptosis (activated caspase-3) in both obese and lean mice but did not alter autophagy (LC3II/LC3I). Nuclear Tbx-1, a marker of metabolically active beige adipocytes, was greater in the adipose of t10-c12 CLA-fed animals. Thus, weight loss achieved via t10-c12 CLA primarily involves fat loss and more cells with Tbx-1 localized to the nucleus, while CR operates through a mechanism that reduces both lean and fat mass and blocks adipocyte differentiation.

Dietary Docosahexaenoic Acid and trans-10, cis-12-Conjugated Linoleic Acid Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue.

Diets containing high n-3 polyunsaturated fatty acids (PUFA) decrease inflammation and the incidence of chronic diseases including cardiovascular disease and nonalcoholic fatty liver disease while trans-fatty acids (TFA) intake increases the incidence of these conditions. Some health benefits of n-3 PUFA are mediated through the impact of their oxygenated metabolites, i.e. oxylipins. The TFA, trans-10, cis-12-conjugated linoleic acid (CLA; 18:2n-6) is associated with adipose tissue (AT) inflammation, oxidative stress, and wasting. We examined the impact of a 4-week feeding of 0, 0.5, and 1.5% docosahexaenoic acid (DHA; 22:6n-3) in the presence and absence of 0.5% CLA on AT oxylipin profiles in female C57BL/6N mice. Esterified oxylipins in AT derived from linoleic acid (LNA), alpha-linolenic acid (ALA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), DHA, and putative from CLA were quantified. CLA containing diets reduced AT mass by ~62%. Compared with the control diet, the DHA diet elevated concentrations of EPA-and DHA-derived alcohols and epoxides and LNA-derived alcohols, reduced ARA-derived alcohols, ketones, epoxides, and 6-keto-prostaglandin (PG) F1α (P < 0.05), and had mixed effects on ALA-derived alcohols. Dietary CLA lowered EPA-, DHA-, and ALA-derived epoxides, ARA-derived ketones and epoxides, and ALA-derived alcohols. While dietary CLA induced variable effects in EPA-, DHA-, and LNA-derived alcohols and LNA-derived ketones, it elevated ARA-derived alcohols and PGF1α, PGF2α, and F2-isoprostanes. DHA counteracted CLA-induced effects in 67, 57, 43, and 29% of total DHA-, ARA-, EPA-, and ALA-derived oxylipins, respectively. Thus, CLA elevated proinflammatory oxylipins while DHA increased anti-inflammatory oxylipins and diminished concentration of CLA-induced pro-inflammatory oxylipins in AT.

Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.

Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA) are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T) biosynthesis, which is known to diminish traumatic brain injury (TBI)-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17)) or Sham injury (craniectomy alone; n = 12) and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16) or saline (n = 13) every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4) by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068), T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p < 0.05), 11-deoxycorticosterone (11-DOC) by 37.5% (from 289.3 ± 42.0 ng/mL to 180.7 ± 3.3 ng/mL), and corticosterone by 50.8% (from 195.1 ± 22.4 ng/mL to 95.9 ± 2.2 ng/mL), by post-surgery day 1. CCI injury induced similar declines in P4, T, 11-DOC and corticosterone (58.9%, 74.6%, 39.4% and 24.6%, respectively) by post-surgery day 1. These results suggest that both Sham surgery and CCI injury induce hypogonadism and hypoadrenalism in adult male rats. CLA treatment did not reverse hypogonadism in Sham (P4: 2.5 ± 1.0 ng/mL; T: 0.9 ± 0.2 ng/mL) or CCI-injured (P4: 2.2 ± 0.9 ng/mL; T: 1.0 ± 0.2 ng/mL, p > 0.05) animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL) and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL) animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s) compared to saline treated Sham animals (8.8 ± 1.7 s). In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s) compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05). These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1) does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse craniectomy- and craniectomy + CCI-induced hypoadrenalism, 2) is detrimental to medium- and long-term spatial learning and memory in craniectomized uninjured rats, 3) limits cognitive recovery following a moderate-severe CCI injury, and 4) does not alter body weight.

The effect of conjugated linoleic acid supplementation on the nutritional status of COPD patients.

BACKGROUND: COPD patients are susceptible to anorexia, reduction of caloric intake, weight loss, and malnutrition. One of the possible mechanisms is the increase of inflammatory markers such as interleukin 1ß (IL1ß), is highly correlated with anorexia. Considering the anti-inflammatory role of conjugated linoleic acid (CLA), this study aimed to investigate the effect of CLA supplementation on the nutritional status of COPD patients. PATIENTS AND METHODS: In a double-blind clinical trial, 93 COPD patients who volunteered to participate in the study and who filled out a written consent form, were randomly assigned to control or supplementation groups. The patients in the supplementation group received 3.2 g of CLA on a daily basis for 6 weeks, while those in the control group received placebo on a daily basis for 6 weeks. For IL1ß assessment, the patients' anthropometric indices and appetite score were checked and their blood samples were collected both before and after the treatment. Moreover, in order to investigate the changes in the caloric intake trend during the study, their dietary intake levels were assessed using 24-hour dietary recall, 3 days a week at the onset, in the 4th week, and at the end of the study. Eventually, 90 patients completed the study. RESULTS: The results demonstrated a significant increase in appetite score (P=0.001), average caloric intake (P=0.01), and macronutrient intake (P<0.05), while a significant decrease was observed in the serum level of IL1ß among the patients of the supplementation group (P=0.008). Meanwhile, although the supplementation group's body mass index was also higher on completion, compared to their own initial state as well as to that in the control group, the differences were not significant (P=0.13). CONCLUSION: The findings of this research indicate that the consumption of CLA supplementation can be effective in regulating the appetite and improving the nutritional status of patients suffering from COPD through adjusting the serum level of IL1ß.

Conjugated linoleic acid (CLA) promotes endurance capacity via peroxisome proliferator-activated receptor δ-mediated mechanism in mice.

Previously, it was reported that conjugated linoleic acid (CLA) with exercise training potentially improved endurance capacity via the peroxisome proliferator-activated receptor δ (PPARδ)-mediated mechanism in mice. This study determined the role of exercise and/or CLA in endurance capacity and PPARδ-associated regulators. Male 129Sv/J mice were fed either control (soybean oil) or CLA (0.5%) containing diets for 4 weeks and were further divided into sedentary or training regimes. CLA supplementation significantly reduced body weight and fat mass independent of exercise during the experimental period. Endurance capacity was significantly improved by CLA supplementation, while no effect of exercise was observed. Similarly, CLA treatment significantly increased expressions of sirtuin 1 and PPARγ coactivator-1α, up-stream regulators of PPARδ, in both sedentary and trained animals. With respect to downstream markers of PPARδ, CLA up-regulated the key biomarker needed to stimulate mitochondrial biogenesis, nuclear respiratory factor 1. Moreover, CLA supplementation significantly induced overall genes associated with muscle fibers, such as type I (slow-twitch) and type II (fast twitch). Taken together, it suggests that CLA improves endurance capacity independent of mild-intensity exercise via PPARδ-mediated mechanism.

Nutrient Regulation: Conjugated Linoleic Acid's Inflammatory and Browning Properties in Adipose Tissue.

Obesity is the most widespread nutritional disease in the United States. Developing effective and safe strategies to manage excess body weight is therefore of paramount importance. One potential strategy to reduce obesity is to consume conjugated linoleic acid (CLA) supplements containing isomers cis-9, trans-11 and trans-10, cis-12, or trans-10, cis-12 alone. Proposed antiobesity mechanisms of CLA include regulation of (a) adipogenesis, (b) lipid metabolism, (c) inflammation, (d) adipocyte apoptosis, (e) browning or beiging of adipose tissue, and (f) energy metabolism. However, causality of CLA-mediated responses to body fat loss, particularly the linkage between inflammation, thermogenesis, and energy metabolism, is unclear. This review examines whether CLA's antiobesity properties are due to inflammatory signaling and considers CLA's linkage with lipogenesis, lipolysis, thermogenesis, and browning of white and brown adipose tissue. We propose a series of questions and studies to interrogate the role of the sympathetic nervous system in mediating CLA's antiobesity properties.

Twelve weeks CLA supplementation decreases the hip circumference in overweight and obese women. A double-blind, randomized, placebo-controlled trial.

BACKGROUND: Conjugated linoleic acid (CLA) reduces body weight (BW), body fat mass (BFM), and increases or maintains lean body mass in animals. However, the results concerning the effect of CLA on weight reduction in humans are contradictory. The present study aimed to evaluate the effect of CLA supplementation on the BW and anthropometric parameters (waist and hip circumferences) in overweight and obese adult women. METHODS: A total of 74 subjects (BMI: 28-42 kg/m2) were included in a double blind, placebocontrolled trial. Subjects were randomized into two groups, those supplemented with either 3.0 g/d CLA or with placebo (sunflower oil) for 12 weeks. RESULTS: CLA significantly decreased the hip circumferences compared to placebo (p = 0.016209), but had no effect on body weight, BMI, or waist circumference. The number of subjects with a reduction in hip circumference in the CLA group was significantly larger compared to that in the placebo group (p = 0.0017;  NNT= 2.65; CI [6.27-1.685]). CONCLUSIONS: In conclusion, our findings do not support the hypothesis that 12 weeks CLA supplementation, as dosed in the present study, is effective for body weight reduction in overweight and obese women. However, its local action in decreasing the hip circumference seems to be encouraging and suggests that CLA may represent an attractive dietary supplement.

Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial.

BACKGROUND: Adverse effects of industrially produced trans fatty acids (iTFAs) on the risk of coronary artery disease are well documented in the scientific literature; however, effects of naturally occurring trans fatty acids (TFAs) from ruminant animals (rTFA), such as vaccenic acid (VA) and cis-9,trans-11 conjugated linoleic acid (c9,t11-CLA), are less clear. Although animal and cell studies suggest that VA and c9,t11-CLA may be hypocholesterolemic and antiatherogenic, epidemiologic data comparing rTFAs and iTFAs are inconsistent, and human intervention studies have been limited, underpowered, and not well controlled. OBJECTIVE: We determined the effects of VA, c9,t11-CLA, and iTFA, in the context of highly controlled diets (24 d each), on lipoprotein risk factors compared with a control diet. RESULTS: We conducted a double-blind, randomized, crossover feeding trial in 106 healthy adults [mean ± SD age: 47 ± 10.8 y; body mass index (in kg/m(2)): 28.5 ± 4.0; low-density lipoprotein (LDL) cholesterol: 3.24 ± 0.63 mmol/L]. Diets were designed to have stearic acid replaced with the following TFA isomers (percentage of energy): 0.1% mixed isomers of TFA (control), ∼3% VA, ∼3% iTFA, or 1% c9,t11-CLA. Total dietary fat (34% of energy) and other macronutrients were matched. Total cholesterol (TC), LDL cholesterol, triacylglycerol, lipoprotein(a), and apolipoprotein B were higher after VA than after iTFA; high-density lipoprotein (HDL) cholesterol and apolipoprotein AI also were higher after VA. Compared with control, VA and iTFA both increased TC, LDL cholesterol, ratio of TC to HDL cholesterol, and apolipoprotein B (2-6% change; P < 0.05); VA also increased HDL cholesterol, apolipoprotein AI, apolipoprotein B, and lipoprotein(a) (2-6% change; P < 0.05), whereas iTFA did not. c9,t11-CLA lowered triacylglycerol (P ≤ 0.01) and had no effect on other lipoprotein risk factors. CONCLUSIONS: With respect to risk of cardiovascular disease, these results are consistent with current nutrition labeling guidelines, with the requirement of VA, but not c9,t11-CLA, to be listed under TFA on the Nutrition Facts Panel. This trial was registered at clinicaltrials.gov as NCT00942656.