Conjugated Linoleic Acid Supplementation Research Articles

Conjugated linoleic acid (CLA) reduces intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.

The anti-obesity effect of conjugated linoleic acid (CLA) has been well elucidated, but whether CLA affects fat deposition by regulating intestinal dietary fat absorption remains largely unknown. Thus, this study aimed to investigate the effects of CLA on intestinal fatty acid uptake and chylomicron formation and explore the possible underlying mechanisms. We found that CLA supplementation reduced the intestinal fat absorption in HFD (high fat diet)-fed mice accompanied by the decreased serum TG level, increased fecal lipids and decreased intestinal expression of ApoB48 and MTTP. Correspondingly, c9, t11-CLA, but not t10, c12-CLA induced the reduction of fatty acid uptake and TG content in PA (palmitic acid)-treated MODE-K cells. In the mechanism of fatty acid uptake, c9, t11-CLA inhibited the binding of CD36 with palmitoyltransferase DHHC7, thus leading to the decreases of CD36 palmitoylation level and localization on the cell membrane of the PA-treated MODE-K cells. In the mechanism of chylomicron formation, c9, t11-CLA inhibited the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the PA-treated MODE-K cells. In in vivo verification, CLA supplementation reduced the DHHC7-mediated total and cell membrane CD36 palmitoylation and suppressed the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the jejunum of HFD-fed mice. Altogether, these data showed that CLA reduced intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.

The Effects of Conjugated Linoleic Acid Supplements on Biomarkers of Oxidative Stress in Human Studies: A Systematic Review and Meta-Analysis

Background: Oxidative stress is the leading cause of chronic disorders. The aim of the present study is to assess the effects of conjugated linoleic acid (CLA) supplements on oxidative stress biomarkers in adults.
 Methods: PubMed, Web of Science, Google Scholar, ProQuest, Scopus, and Embase were searched up to December 2020. All clinical trials that evaluated the effect of CLA on malondialdehyde (MDA), GSH-peroxidase (GPX), and 8-IsoprostanesF2α (8-iso-PGF2α) were included.
 Results: Twelve eligible studies were included in the meta-analysis. A significant increase was observed in 8-iso-PGF2α level (SMD=1.48 nmol/mmol of creatinine; 95% CI: 1.11 to 1.85) with low heterogeneity level (I2= 31.5%, and P=0.199). This effect was also significant in both subgroups of healthy and metabolic disorder individuals. Moreover, after Hartung-Knapp adjustment, the results remained significant. No significant changes were found in MDA (SMD=-0.34 µmol/l; 95% CI: -0.82 to 0.14) and GPX (SMD=0.31 U/gHb; 95% CI: -0.03 to 0.66) levels. However, after Hartung-Knapp adjustment, the results became significant for GPX level (SMD=0.31, 95% CI: 0.04 to 0.59).
 Conclusion: CLA supplementation could significantly increase some markers of oxidative stress such as 8-iso-PGF2α level and GPX level, without any significant effect on MDA level.

Micellized conjugated linoleic acid as an immune modifier feed additive for suckling calves

This study was attempted to assess the effects of micellized conjugated linoleic acid (CLA) as a feed additive for suckling calves on their growth performance and blood metabolic, oxidative and immune parameters. Forty-eight Holstein calves were divided among four experimental groups (12 calves/treatment) including: 1) calves with no CLA supplementation (CON), 2) calves supplemented with 1 gr CLA/d as micellized form by dissolving 5 mL/d of a CLA contained emulsion in milk (CLA1), 3) calves supplemented with 2 gr CLA/d as micellized form by dissolving 10 mL/d of a CLA contained emulsion in milk (CLA2) and 4) calves supplemented with 3 gr CLA/d as micellized form by dissolving 15 mL/d of a CLA contained emulsion in milk (CLA3). Calves in the CON group received 10 mL of the emulsion medium with no CLA. Feeding micellized CLA via whole milk resulted in a linear increase in blood concentration of glucose on d 40 (P=0.04), and total protein (P

Is milk fat globule size correlated with milk fat content in Ruminants?

In milk, fat exists in the form of milk fat globules (MFGs). The average size (average fat globules of different particle sizes) is the most common parameter when describing MFG size. There are different views on whether there is a correlation between MFG size and milk fat content. Is the MFG size correlated with milk fat content in ruminants? To address this question, we conducted two experiments. In experiment Ⅰ, dairy cows (n = 40) and dairy goats (n = 30) were each divided into a normal group and a low-fat group according to the milk fat content. In experiment Ⅱ, dairy cows (n = 16) and dairy goats (n = 12) were each divided into a normal group and a conjugated linoleic acid (CLA)-induced low-fat group. The normal groups were fed a basal diet, and the CLA-induced low-fat groups were fed the basal diet + 300 g/d CLA (cows) or the basal diet + 90 g/d CLA (goats). In both experiments, we determined the correlation between MFG size and milk composition and MFG distribution. The results showed that in the normal and low-fat groups of cows and goats, MFG size was not correlated with milk fat, protein, or lactose content or fat-to-protein ratio. Additionally, there was no difference in the distribution of large, medium, and small MFGs (P > 0.05). However, in the CLA-induced low-fat groups, we found a correlation between MFG size and milk fat content and fat-to-protein ratio (R2 > 0.3). Moreover, there was a significant change in the size distribution of MFGs. Therefore, in natural milk, MFG size was not correlated with milk fat content. Following CLA supplementation, MFG size was correlated with milk fat content. Our findings revealed that CLA and not milk fat affects MFG distribution and size.

The effects of conjugated linoleic acid supplementation on anthropometrics and body composition indices in adults: a systematic review and dose-response meta-analysis.

Prior meta-analytic investigations over a decade ago rather inconclusively indicated that conjugated linoleic acid (CLA) supplementation could improve anthropometric and body composition indices in the general adult population. More recent investigations have emerged, and an up-to-date systematic review and meta-analysis on this topic must be improved. Therefore, this investigation provides a comprehensive systematic review and meta-analysis of randomised controlled trials (RCT) on the impact of CLA supplementation on anthropometric and body composition (body mass (BM), BMI, waist circumference (WC), fat mass (FM), body fat percentage (BFP) and fat-free mass (FFM)) markers in adults. Online databases search, including PubMed, Scopus, the Cochrane Library and Web of Science up to March 2022, were utilised to retrieve RCT examining the effect of CLA supplementation on anthropometric and body composition markers in adults. Meta-analysis was carried out using a random-effects model. The I2 index was used as an index of statistical heterogeneity of RCT. Among the initial 8351 studies identified from electronic databases search, seventy RCT with ninety-six effect sizes involving 4159 participants were included for data analyses. The results of random-effects modelling demonstrated that CLA supplementation significantly reduced BM (weighted mean difference (WMD): -0·35, 95 % CI (-0·54, -0·15), P < 0·001), BMI (WMD: -0·15, 95 % CI (-0·24, -0·06), P = 0·001), WC (WMD: -0·62, 95% CI (-1·04, -0·20), P = 0·004), FM (WMD: -0·44, 95 % CI (-0·66, -0·23), P < 0·001), BFP (WMD: -0·77 %, 95 % CI (-1·09, -0·45), P < 0·001) and increased FFM (WMD: 0·27, 95 % CI (0·09, 0·45), P = 0·003). The high-quality subgroup showed that CLA supplementation fails to change FM and BFP. However, according to high-quality studies, CLA intake resulted in small but significant increases in FFM and decreases in BM and BMI. This meta-analysis study suggests that CLA supplementation may result in a small but significant improvement in anthropometric and body composition markers in an adult population. However, data from high-quality studies failed to show CLA's body fat-lowering properties. Moreover, it should be noted that the weight-loss properties of CLA were small and may not reach clinical importance.

Review: Effect of essential fatty acids and conjugated linoleic acid on the adaptive physiology of dairy cows during the transition period.

Cows fed total mixed rations (silage-based) may not receive as much essential fatty acids (EFAs) and conjugated linoleic acids (CLAs) as cows fed pasture-based rations (fresh grass) containing rich sources of polyunsaturated fatty acids. CLA-induced milk fat depression allows dairy cows to conserve more metabolisable energy, thereby shortening the state of negative energy balance and reducing excessive fat mobilisation at early lactation. EFAs, particularly α-linolenic acid, exert anti-inflammatory and antioxidative properties, thereby modulating immune functions. Thus, combined EFA and CLA supplementation seems to be an effective nutritional strategy to relieve energy metabolism and to improve immune response, which are often compromised during the transition from late pregnancy to lactation in high-yielding dairy cows. There has been extensive research on this idea over the last two decades, and despite promising results, several interfering factors have led to varying findings, making it difficult to conclude whether and under what conditions EFA and CLA supplementations are beneficial for dairy cows during the transition period. This article reviews the latest studies on the effects of EFA and CLA supplementation, alone or in combination, on dairy cow metabolism and health during various stages around parturition. Our review article summarises and provides novel insights into the mechanisms by which EFA and/or CLA influence markers of metabolism, energy homeostasis and partitioning, immunity, and inflammation revealed by a deep molecular phenotyping.

Abomasal infusion of essential fatty acids and conjugated linoleic acid during late pregnancy and early lactation affects immunohematological and oxidative stress markers in dairy cows

Oxidative stress and inflammation, as natural parts of metabolic adaptations during the transition from late gestation to early lactation, are critical indicators of dairy cows' metabolic health. This study was designed to investigate the effects of abomasal infusion of essential fatty acids (EFA), particularly α-linolenic acid, and conjugated linoleic acid (CLA) on plasma, erythrocyte, and liver markers of oxidative stress in dairy cows during the transition period. Rumen-cannulated German Holstein cows (n = 38) in their second lactation (11,101 ± 1,118 kg milk/305 d, mean ± standard deviation) were abomasally infused with one of the following treatments from d -63 antepartum until d 63 postpartum (PP): CTRL (n = 9; 76 g/d coconut oil); EFA (n = 9; 78 g/d linseed plus 4 g/d safflower oil); CLA (n = 10; isomers cis-9,trans-11 and trans-10,cis-12 CLA; 38 g/d); and EFA+CLA (n = 10; 120 g/d). Hematological parameters as well as markers of oxidative status were measured in plasma, erythrocytes, and liver before and after calving. Immunohematological parameters, including erythrocyte number, hematocrit, hemoglobin, mean corpuscular hemoglobin, leukocytes, and basophils, were affected by time, and their peak levels were observed on the day after calving. The oxidative stress markers glutathione peroxidase 1 and reactive oxygen metabolites in plasma and erythrocytes were both affected by time, exhibiting the highest levels on d 1 PP, whereas β-carotene, retinol, and tocopherol were at their lowest levels at the same time. Immunohematological parameters were only marginally affected by fatty acid treatment in a time-dependent manner. As such, lymphocyte and atypical lymphocyte counts were both significantly highest in the groups that received EFA at d 1 PP. Moreover, EFA supplementation increased the mean corpuscular volume and showed a trend for induction of mean corpuscular hemoglobin compared with the CLA group during the transition period. The PP mean thrombocyte volume was higher in the EFA than in the CLA group (except for d 28) and both EFA and CLA reduced number of thrombocytes and thrombocrit at distinct time points. Hepatic mRNA abundance of markers related to oxidative status, including glutathione peroxidase (GPX-1) and catalase (CAT), was lower (P < 0.05) in EFA-treated than non-EFA-treated cows at d 28 PP. Dairy cows at the onset of lactation were characterized by induced markers of both oxidative stress and inflammation. Supplementing EFA and CLA had minor and time-dependent effects on markers of oxidative stress in plasma, erythrocytes, and liver. A comparison of EFA supplementation with CLA or CTRL showed higher immunohematological response at d 1 PP and lower hepatic antioxidant levels by d 28 PP. Supplementation with EFA+CLA had only a minor effect on oxidative markers, which were more similar to those with the EFA treatment. Altogether, despite the time-dependent differences, the current findings show only minor effects of EFA and CLA supplementation in the prevention of early lactation-induced oxidative stress.

Conjugated linoleic acid supplementation changes prostaglandin concentration ratio and alters the expression of genes involved in maternal-fetal recognition from bovine trophoblast cells in vitro

Early embryonic mortality caused by maternal-fetal recognition failure in the three weeks after fertilization represents a major cause of reproductive inefficiency in the cattle industry. Modifying the amounts and ratios of prostaglandin (PG) F2α and PGE2 can benefit the establishment of pregnancy in cattle. Adding conjugated linoleic acid (CLA) to endometrial and fetal cells culture affects PG synthesis, but its effect on bovine trophoblast cells (CT-1) is unknown. The aim of this study was to determine the effects of CLA (a mixture of cis- and trans-9, 11- and −10,12-octadecadienoic acids) on PGE2 and PGF2α synthesis and the expression of transcripts involved with maternal-fetal recognition of bovine trophectoderm. Cultures of CT-1 were exposed to CLA for 24, 48 and 72 h. Transcript abundance was determined by qRT-PCR and hormone profiles were quantified by ELISA. The PGE2 and PGF2α concentrations were reduced in the culture medium of CLA-exposed CT-1 compared to that of unexposed cells. Furthermore, CLA supplementation increased the PGE2:PGF2α ratio in CT-1 and had a quadratic effect (P < 0.05) on the relative expression of MMP9, PTGES2, and PTGER4. The relative expression levels of PTGER4 were reduced (P < 0.05) in CT-1 cultured with 100 μM CLA than in the unsupplemented and 10 μM-CLA groups. Treatment of CT-1 with CLA decreased PGE2 and PGF2α synthesis but a biphasic effect of CLA was observed on the PGE2:PGF2α ratio and relative abundance of transcripts with 10 μM CLA providing maximal improvements in each endpoint. Our data suggest that CLA may influence eicosanoid metabolic process and extracellular matrix remodeling.

The effects of conjugated linoleic acid supplementation on inflammatory cytokines and adipokines in adults: A GRADE-assessed systematic review and dose-response meta-analysis.

Many studies have investigated the effect of conjugated linoleic acid (CLA) supplementation on inflammatory cytokines and adipokines. However, the results of these studies are not consistent. Therefore, this systematic review and meta-analysis were designed to comprehensively evaluate the effect of CLA supplementation on inflammatory cytokines and adipokines. Randomized controlled trials (RCTs) examining the effects of CLA supplementation on C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), adiponectin, and leptin, published up to March 2022, were identified through PubMed, SCOPUS, and ISI Web of Science databases. A random-effects model was used to calculate weighted mean differences (WMDs) with 95% confidence intervals (CI) for 42 studies that included 1,109 participants. Findings from 42 studies with 58 arms indicated that CLA supplementation significantly decreased IL-6 and TNF-α levels and also slightly increased CRP levels. However, adiponectin and leptin levels did not change after CLA supplementation. A subgroup analysis found that CLA supplementation reduced adiponectin and leptin in women. Our results demonstrated that CLA supplementation increased CRP levels and decreased TNF-α and IL-6 levels. Therefore, it seems that CLA can have both proinflammatory and anti-inflammatory roles. https://www.crd.york.ac.uk/prospero/, identifier (CRD42022331110).

Size, numberand phospholipid composition of milk fat globules are affected by dietary conjugated linoleic acid.

Milk fat globules (MFGs) surround the triacylglycerol core that composes milk fat. The aim of this study isto induce milk fat depression via dietary conjugated linoleic acid (CLA) supplementation to study MFG size parameters, numberand glycerophospholipid composition. Eighteen Holstein dairy cows (136 ± 28 days in milk, 571 ± 37.9 kg body weight, 27.6 ± 2.1 kg milk/day) were selected and randomly assigned to a control or CLA group for a 14-dayperiod. Cows were fed a basal diet (control, n = 8) or the control plus 400 g/day CLA (C18:2 cis-9, trans-11 38.1% and C18:2 trans-10, cis-12 36.8%) (n = 10) for 7 days after which the CLA group was switched to the basal diet for another 7 days along with the control group. Cow performance, milk composition, MFG size and numbers were measured daily. On the seventh day after the start of the experiment, milk samples were identified and the quantification of glycerophospholipid compounds, and RNA were isolated from milk fat samples for a real-time polymerase chain reaction. Compared with control, at Day 7 from the start of feeding, supplemental CLA did not affect milk production (28.09vs. 28.50 kg/day), dry matter intake (14.9vs. 15.4 kg/day), or milk protein (3.55/100vs. 3.70 g/100 ml) and lactose contents (5.11/100vs. 5.17 g/100 ml). However, although the specific surface area of MFG (2138vs. 1815 m²/kg) was greater, CLA reduced milk fat content (1.95/100vs 3.64 g/100 ml on Day 7) and particle size parameters of MFG. The number of MFG gradually decreased until Day 7 of feeding, and then increased by Day 14 (2.96 × 109 on Day 1, 1.63 × 109 on Day 7 and 2.28 × 109 on Day 14) in the CLA group. Compared with control, glycerophospholipid analysis revealed that concentrations of phosphatidylcholine (PC) (e.g., PC [16:0/18:1] 20322vs. 29793 nmol/L), lysophosphatidylethanolamine (LPE) (e.g., LPE [18:1] 956vs. 4610 nmol/L)and phosphatidylethanolamine (PE) (e.g., PE [16:0/18:1] 7000 vs. 9769 nmol/L) in milk lipids decreased during CLA feeding. In contrast, concentrations of phosphatidylinositol (PI) (e.g., PI [18:0/18:1] 4052vs. 1799 nmol/L) and phosphatidylserine (PS) (e.g., PS [18:1/18:2] 9500 vs. 6843 nmol/L) increased. The messenger RNA abundance of fatty acid synthase, diacylglycerol O-acyltransferase 1, glycerol-3-phosphate acyltransferase 4and phosphate cytidylyltransferase 1, choline, alpha (PCYT1A) were downregulated in the CLA group, confirming published data demonstrating a negative effect of CLA on lipogenesis in the mammary gland. Overall, these results provided evidence for the important role of lipogenic gene expression in the regulation of MFG size, number and glycerophospholipid composition.

Milk fat globule membrane proteins are involved in controlling the size of milk fat globules during conjugated linoleic acid-induced milk fat depression.

Milk fat globule membrane (MFGM) proteins surround the triacylglycerol core comprising milk fat globules (MFG). We previously detected a decrease in the size of fat globules during conjugated linoleic acid (CLA)-induced milk fat depression (MFD), and other studies have reported that some MFGM proteins play a central role in regulating mammary cellular lipid droplet size. However, little is known about the relationship between MFD, MFG size, and MFGM proteins in bovine milk. The aim of this study was to investigate the profile of MFGM proteins during MFD induced by CLA. Sixteen mid-lactating Holstein cows (145 ± 24 d in milk) with similar body condition and parity were divided into control and CLA groups over a 10-d period. Cows were fed a basal diet (control, n = 8) or control plus 15 g/kg of dry matter (DM) CLA (n = 8) to induce MFD. Cow performance, milk composition, and MFG size were measured daily. On d 10, MFGM proteins were extracted and identified by quantitative proteomic analysis, and western blotting was used to verify a subset of the identified MFGM proteins. Compared with controls, supplemental CLA did not affect milk production, DM intake, or milk protein and lactose contents. However, CLA reduced milk fat content (3.73 g/100 mL vs. 2.47 g/100 mL) and the size parameters volume-related diameter D[4,3] (3.72 μm vs. 3.35 μm) and surface area-related diameter D[3,2] (3.13 μm vs. 2.80 μm), but increased specific surface area of MFG (1,905 m2/kg vs. 2,188 m2/kg). In total, 177 differentially expressed proteins were detected in milk from cows with CLA-induced MFD, 60 of which were upregulated and 117 downregulated. Correlation analysis showed that MFG size was negatively correlated with various proteins, including XDH and FABP3, and positively correlated with MFG-E8, RAB19, and APOA1. The results provide evidence for an important role of MFGM proteins in regulating MFG diameter, and they facilitate a mechanistic understanding of diet-induced MFD.

Impact of safflower oil derived conjugated linoleic acid supplementation on fatty acids profile, lipolysis and sensory properties of cheddar cheese

ABSTRACT Nutritionists recommend to consume 3 g Conjugated linoleic acid (CLA) to prevent cancers, cardiovascular diseases, diabetes, obesity and other lifestyle-related disorders. To fulfill the daily requirements of CLA, large proportions of dairy and meat products have to be included in the dietary plan that may have negative impacts such as excessive intake of fat, cholesterol, and lactose. Current investigation was aimed to determine the effect of safflower oil derived CLA on fatty acids composition, lipolysis and sensory properties of cheddar cheese. Safflower oil-derived conjugated linoleic acid (CLA) was added to cheddar cheese at four levels i.e. 1%, 2%, 3% and 4% concentrations (T1, T2, T3 & T4), cheese without CLA supplement was used as control, vacuum packaged samples were ripened at 6–8°C for 90 days. Analysis of CLA supplement revealed that concentrations of ∆9c,11 t-18:2, ∆10 t,12c-18:2, ∆9c,11c-18:2, ∆9 t, 11c-18:2 were 52.16, 44.37, 0.27 and 0.55 mg/100 g. In control, concentrations of ∆9c,11 t-18:2 and ∆10 t,12c-18:2 was 0.24% and 0.07% with a total CLA content of 0.31%. In T3, concentrations of ∆9c,11 t-18:2, ∆10 t,12c-18:2, ∆9c,11c-18:2 and ∆9 t, 11c-18:2 were 1.12, 3.82, 1.63, 2.77 (total CLA 8.34mg100g). In T4, concentrations of ∆9c,11 t-18:2, ∆10 t,12c-18:2, ∆9c,11c-18:2 and ∆9 t, 11c-18:2, were 1.47, 3.50, 3.25 and 3.44% (total CLA 11.67 mg/100 g). Supplementation of cheddar cheese at all four levels significantly increased the concentrations of lactic acid, citric acid, propionic and acetic acids. After 90 days of ripening, free fatty acids in control, T1, T2, T3 and T4 were 0.14, 0.19, 0.23, 0.29 and 0.37% with no difference in composition and sensory properties. These results suggested that CLA content of cheddar cheese can be successfully increased with safflower oil-derived CLA supplement.

Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells.

Background A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers' attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis. Hepatocyte nuclear factor 4 alpha (HNF4α) is the key hepatogenesis transcription factor and its upregulation may decrease the invasiveness of cancerous cells by suppressing epithelial-mesenchymal transition (EMT). This study aimed to evaluate the effect of conjugated linoleic acid (CLA) treatment, natural ligand of HNF4α, on the proliferation, migration, and invasion capacities of HCC cells in vitro. Materials and Method. Sk-Hep-1 and Hep-3B cells were treated with different doses of CLA or BIM5078 [1-(2′-chloro-5′-nitrobenzenesulfonyl)−2-methylbenzimidazole], an HNF4α antagonist. The expression levels of HNF4a and EMT related genes were evaluated and associated to hepatocytic functionalities, migration, and colony formation capacities, as well as to viability and proliferation rate of HCC cells. Results In both HCC lines, CLA treatment induced HNF4α expression in parallel to significantly decreased EMT marker levels, migration, colony formation capacity, and proliferation rate, whereas BIM5078 treatment resulted in the opposite effects. Moreover, CLA supplementation also upregulated ALB, ZO1, and HNF4α proteins as well as glycogen storage capacity in the treated HCC cells. Conclusion CLA treatment can induce a remarkable hepatocytic differentiation in HCC cells and attenuates cancerous features. This could be as a result of HNF4a induction and EMT inhibition.

The effect of conjugated linoleic acid supplementation on oxidative stress markers: A systematic review and meta-analysis of randomized controlled trials.

Recent trial studies have found that conjugated linoleic acid (CLA) supplementation beneficially reduces oxidative stress markers but, there is no definitive consensus on this context. The present systematic review and meta-analysis aimed to investigate the effect of CLA supplementation on oxidative stress parameters. We searched PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases until September 2021 to identify randomized controlled trials (RCTs) assessing CLA supplementation effects on oxidative markers including malondialdehyde (MDA), 8-isoprostanesF2α (8-iso-PGF2α), and glutathione peroxidase (GPx). Summary estimates and corresponding 95% confidence intervals (CI) were derived via the DerSimonian and Laird method using a random-effects model. A total of 11 RCTs were included. The obtained results show that CLA supplementation caused a significant decrease in MDA concentrations (Hedges's:-0.35; 95% CI:-0.70 to-0.01, P=0.04, I2=62.1%, n=7), and also significantly increased 8-iso-PGF2α levels (Hedges's: 1.45; 95% CI: 0.98 to 1.91, P˂0.001, I2=42.9%, n=4). However, the results showed that supplementation with CLA did not significantly change the concentrations of GPx (Hedges's: 0.30; 95% CI:-0.04 to 0.64, P=0.08, I2=0.0%, n=3). It seems this supplement can be used as a dietary supplement to improve oxidative stress parameters. However, further studies are required to demonstrate present results.

Targeted inhibition of PPARα ameliorates CLA-induced hypercholesterolemia via hepatic cholesterol biosynthesis reprogramming.

Disruption of lipid metabolism is largely linked to metabolic disorders, such as hypercholesterolemia (HCL) and liver steatosis. While cholesterol metabolic re-programmers can serve as targets for relevant interventions. Here we explored the dietary conjugated linoleic acids (CLA)-induced HCL in mice and the molecular regulation behind it. A high dose of CLA supplementation in the diet was used to induce HCL in mice and was found to cause a hyper-activated cholesterol biosynthesis programme in the liver, leading to cholesterol metabolism dysregulation. The effects of a small-molecule drug targeting PPARα, i.e., GW6471 were studied in vivo in mice fed diets with CLA supplementation for 28days, and in primary hepatocytes derived from HCL-mice in vitro. We demonstrate that CLA induced HCL and liver steatosis through multiple pathways. Among which was the PPARα-mediated cholesterogenesis. It was found to cooperate with SREBP2 via binding to Hmgcr and Dhcr7 (genes encoding key enzymes of the cholesterol biosynthetic pathway) and recruits the histone marks H3K27ac and H3K4me1 and cofactors. PPARα inhibition disrupts its physical association with SREBP2 by blocking cobinding of PPARα and SREBP2 to the genomic DNA response element. We showed that NR RORγ functions as an essential mediator that facilitates the interaction of PPARα and SREBP2 to modulate the cholesterol biosynthesis genes expression. Our study unravels that the small-molecule compound GW6471 exerts an attractive therapeutic effect for CLA-induced HCL, involving multiple pathways with the "PPARα-RORγ-SREBP2" being a potential complex player in this hepatic cholesterol biosynthesis programming.

Effect of Conjugated Linoleic Acid (CLA) Supplementation on Expression of B-Cell Lymphoma-2 (Bcl-2) in the Bladder Epithelium of Wistar (Rattus norvegicus) Rats Exposed to Cigarette Smoke.

Bladder carcinoma is the 10th most common cancer in the world with an incidence about 3% of all cancers. The risk factor for smoking is found in 81% of all cases of bladder carcinoma. One of the protein groups associated with bladder urothelial carcinoma is B-Cell Lymphoma-2 (Bcl-2). Nicotine-derived nitrosamine ketone (NNK) contained in cigarette smoke would increase the proliferation of cancer cells through increased the expression of Bcl-2. The expression of Bcl-2 could be suppressed in the presence of Conjugated Linoleic Acid (CLA), a polyunsaturated fatty acid that has role in reducing the risk of cancer development which is reported in several studies, and then stimulate cell apoptosis. To determine the effect of CLA supplementation on Bcl-2 expression in the bladder of rats which is exposed to cigarette smoke. The study is an experimental study with true experimental posttest only control group design on Wistar rats. Sample was divided into 2 case groups: 0.5% of diet (125 mg) CLA supplementation in group A, 1% of diet (250 mg) CLA in group B; and 2 control groups: group without CLA supplementation (group C) as positive control and without cigarette smoke exposure (group D) as negative control. The study takes 60 days of exposure and then Bcl-2 expression on bladder epithelial was evaluated by immunohistochemistry staining. The results descriptively showed that rats in group C has an average Bcl-2 expression of 25.8±7.33%, while rats in group D has an average Bcl-2 expression 14.1±7.73% which means cigarette smoke exposure has been shown to increase the expression of Bcl-2 by 45.35% (p=0.019) in the bladder mucosa of experimental animals. Group B obtained an average Bcl-2 expression was 14.2±9.6% and has a significant difference when compared to group C, it shows that the addition of 1% CLA would reduce the expression of Bcl-2 by 44.96% (p=0.032). However, for group A, group with 0.5% diet of CLA supplementation did not showed decrease of Bcl-2 expression when compared to the group C (p=0.37). Conjugated Linoleic Acid (CLA) supplementation 1% of diet can reduce Bcl-2 expression in bladder epithelium of wistar rats (Rattus norvegicus) exposed to cigarette smoke.

Longitudinal liver proteome profiling in dairy cows during the transition from gestation to lactation: Investigating metabolic adaptations and their interactions with fatty acids supplementation via repeated measurements ANOVA-simultaneous component analysis

Repeated measurements analysis of variance – simultaneous component analysis (ASCA) has been developed to handle complex longitudinal omics datasets and combine novel information with existing data. Herein, we aimed at applying ASCA to 64 liver proteomes collected at 4-time points (day −21, +1, +28, and + 63 relative to parturition) from 16 Holstein cows treated from 9 wk. antepartum to 9 wk. postpartum (PP) with coconut oil (CTRL) or a mixture of essential fatty acids (EFA) and conjugated linoleic acid (CLA) (EFA + CLA). The ASCA modeled 116, 43, and 97 differentially abundant proteins (DAP) during the transition to lactation, between CTRL and EFA + CLA, and their interaction, respectively. Time-dependent DAP were annotated to pathways related to the metabolism of carbohydrates, FA, and amino acid in the PP period. The DAP between FA and the interaction effect were annotated to the metabolism of xenobiotics by cytochrome P450, drug metabolism - cytochrome P450, retinol metabolism, and steroid hormone biosynthesis. Collectively, ASCA provided novel information on molecular markers of metabolic adaptations and their interactions with EFA + CLA supplementation. Bioinformatics analysis suggested that supplemental EFA + CLA amplified hepatic FA oxidation; cytochrome P450 was enriched to maintain metabolic homeostasis by oxidation/detoxification of endogenous compounds and xenobiotics. SignificanceThis report is among the first ones applying repeated measurement analysis of variance–simultaneous component analysis (ASCA) to deal with longitudinal proteomics results. ASCA separately identified differentially abundant proteins (DAP) in ‘transition time’, ‘between fatty acid treatments’, and ‘their interaction’. We first identified the molecular signature of hepatic metabolic adaptations during postpartum negative energy balance; the enriched pathways were well-known pathways related to mobilizing fatty acids (FA) and amino acids to support continuous energy production through fatty acid oxidation, TCA cycle, and gluconeogenesis. Some of the DAP were not previously reported in transition dairy cows. Secondly, we provide novel information on the mechanisms by which supplemented essential FA and conjugated linoleic acids interact with hepatic metabolism. In this regard, FA amplified hepatic detoxifying and oxidation capacity through ligand activation of nuclear receptors. Finally, we briefly compared the strengths and weaknesses of the ASCA model with PLS-DA and outlined why these methods are complementary.

The Effects of Conjugated Linoleic Acid and Berberine Supplementation on Markers of Allopurinol Activated Oxidative Stress in Broiler Chickens

Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.

Effects of Polyunsaturated Fatty Acids Supplementation on the Meat Quality of Pigs: A Meta-Analysis

Polyunsaturated fatty acids (PUFAs) supplementation has been widely discussed as a strategy for improving meat quality in pig production, but the effects are inconsistent. This meta-analysis was performed to comprehensively evaluate its effects on the meat quality and growth performance of pigs. We searched the PubMed and the Web of Science databases (articles published from January 1, 2000 to October 16, 2020) and compared PUFAs-supplemented diets with control diets. We identified 1,670 studies, of which 14 (with data for 752 pigs) were included in our meta-analysis. The subgroup analysis was classified as PUFA source [conjugated linoleic acid (CLA) or linseed], concentration (high or low concentration), and initial stage (growing or finishing pigs). Our analysis found that PUFA supplementation increased the intramuscular fat (IMF) content (WMD = 0.467%, 95% CI: 0.312–0.621, p < 0.001), decreased the meat color L* (WMD = −0.636, 95% CI: −1.225 to −0.047, p = 0.034), and pH 24 h (WMD = −0.021, 95% CI: −0.032 to −0.009, p < 0.001) but had no influence on drip loss, meat color a* and b*, pH 45 min, and growth performance. CLA supplementation improved IMF content (WMD = 0.542%, 95% CI: 0.343–0.741, p < 0.001) and reduced meat color b* (WMD = −0.194, 95% CI: −0.344 to −0.044, p = 0.011). Linseed supplementation increased IMF content (WMD = 0.307%, 95% CI: 0.047–0.566, p = 0.021), decreased meat color L* (WMD = −1.740, 95% CI: −3.267 to −0.213, p = 0.026), and pH 24 h (WMD = 0.034, 95% CI: −0.049 to −0.018, p < 0.001). We discovered an increase on the IMF content in both high and low concentration PUFA supplementation (WMD = 0.461%, 95% CI: −0.344 to −0.044, p < 0.001; WMD = 0.456%, 95% CI: 0.276–0.635, p < 0.001). Furthermore, we also found the effects of PUFA supplementation on meat color L* and pH 24 h are concentration- and stage-dependent. PUFA supplementation can improve the meat quality of pigs, which mainly emerges in greatly increasing IMF content.

Effects of conjugated linoleic acid supplementation on serum leptin levels, oxidative stress factors and tumor marker in rectal cancer patients undergoing preoperative chemoradiotherapy

BACKGROUND: Inflammation is considered as one of the major factors in chemoradiotherapy toxicity. It has been reported that conjugated linoleic acid (CLA) has anti-inflammatory properties. OBJECTIVE: The aim of this study was to assess the effect of CLA supplementation on serum levels of leptin, interleukin 8 (IL-8), malondialdehyde (MDA), total antioxidant status (TAS), and carcinoembryonic antigen (CEA) in rectal cancer patients treated with chemoradiotherapy. METHODS: In this study, 34 rectal cancer patients were allocated to either the CLA group, who received four 1000 mg capsules (each capsule containing 760 mg CLA; 4 capsules providing 3 g CLA) 3 times/day, or the placebo group, who received 4 placebo capsules 3 times/day, for 6 weeks. RESULTS: The mean serum leptin level insignificantly increased in both groups; however, this elevation was remarkable in the CLA group. CLA supplementation reduced IL-8 by –0.62 pg/mL while placebo supplementation decreased it by –0.44 pg/mL. CEA levels were decreased by CLA supplementation, while its reduction in the placebo group was negligible compared to the CLA group. The elevation of MDA levels after CLA supplementation was about half of the placebo group in the CLA group. CONCLUSION: Since this study was the first to assess the effect of CLA supplementation on a small number of cancer patients, it is suggested further studies are conducted on larger sample size with various doses of CLA to obtain more clear results.