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.

Conjugated Linoleic Acid Ameliorates High Fat-Induced Insulin Resistance via Regulating Gut Microbiota-Host Metabolic and Immunomodulatory Interactions.

Interaction between gut microbiota, host immunity and metabolism has been suggested to crucially affect the development of insulin resistance (IR). This study aims to investigate how gut microbiota, inflammatory responses and metabolism in individuals with IR are affected by the supplementation of conjugated linoleic acid (CLA) and how this subsequently affects the pathophysiology of IR by using a high-fat diet-induced IR mouse model. Serum biochemical indices showed that 400 mg/kg body weight of CLA effectively attenuated hyperglycemia, hyperlipidemia, glucose intolerance and IR, while also promoting antioxidant capacities. Histomorphology, gene and protein expression analysis revealed that CLA reduced fat deposition and inflammation, and enhanced fatty acid oxidation, insulin signaling and glucose transport in adipose tissue or liver. Hepatic transcriptome analysis confirmed that CLA inhibited inflammatory signaling pathways and promoted insulin, PI3K-Akt and AMPK signaling pathways, as well as linoleic acid, arachidonic acid, arginine and proline metabolism. Gut microbiome analysis further revealed that these effects were highly associated with the enriched bacteria that showed positive correlation with the production of short-chain fatty acids (SCFAs), as well as the improved SCFAs production simultaneously. This study highlights the therapeutic actions of CLA on ameliorating IR via regulating microbiota-host metabolic and immunomodulatory interactions, which have important implications for IR control.

Dietary supplementation of phytoncide and soybean oil increases milk conjugated linoleic acid and depresses methane emissions in Holstein dairy cows.

The objective of this study was to determine whether adding phytoncide oil (PO) and soybean oil (SBO) to the dairy cow diet could increase milk conjugated linoleic acid (CLA) and depress methane (CH4) emissions in Holstein dairy cows. Rumen fermentation was conducted at four levels of SBO (0, 1, 2, and 4%, on DM basis) and two levels of PO (0 and 0.1%, on DM basis) with in vitro experiment. To evaluate blood parameters, fecal microbe population, milk yield and fatty acid compositions, and CH4 production, in vivo experiment was conducted using 38 Holstein dairy cows divided into two groups of control (fed TMR) and treatment (fed TMR with 0.1% PO and 2% SBO as DM basis). In the in vitro study (Experiment 1), PO or SBO did not affect rumen pH. However, SBO tended to decrease ruminal ammonia-N (p = 0.099). Additionally, PO or SBO significantly decreased total gas production (p = 0.041 and p = 0.034, respectively). Both PO and SBO significantly decreased CH4 production (p < 0.05). In addition, PO significantly increased both CLA isomers (c9, t11 and t10, c12 CLA) (p < 0.001). Collectively, 0.1% PO and 2% SBO were selected resulting in most effectively improved CLA and decreased CH4 production. In the in vivo study (Experiment 2), 0.1% PO with 2% SBO (PSO) did not affect complete blood count. However, it decreased blood urea nitrogen and magnesium levels in blood (p = 0.021 and p = 0.01, respectively). PSO treatment decreased pathogenic microbes (p < 0.05). It increased milk yield (p = 0.017) but decreased percentage of milk fat (p = 0.013) and MUN level (p < 0.01). In addition, PSO treatment increased both the concentration of CLA and PUFA in milk fat (p < 0.01). Finally, it decreased CH4 emissions from dairy cows. These results provide compelling evidence that a diet supplemented with PSO can simultaneously increase CLA concentration and decrease CH4 production with no influence on the amount of milk fat (kg/day) in Holstein dairy cows.

Facile adipocyte uptake and liver/adipose tissue delivery of conjugated linoleic acid-loaded tocol nanocarriers for a synergistic anti-adipogenesis effect.

Obesity is a major risk to human health. Adipogenesis is blocked by α-tocopherol and conjugated linoleic acid (CLA). However, their effect at preventing obesity is uncertain. The effectiveness of the bioactive agents is associated with their delivery method. Herein, we designed CLA-loaded tocol nanostructured lipid carriers (NLCs) for enhancing the anti-adipogenic activity of α-tocopherol and CLA. Adipogenesis inhibition by the nanocarriers was examined using an in vitro adipocyte model and an in vivo rat model fed a high fat diet (HFD). The targeting of the tocol NLCs into adipocytes and adipose tissues were also investigated. A synergistic anti-adipogenesis effect was observed for the combination of free α-tocopherol and CLA. Nanoparticles with different amounts of solid lipid were developed with an average size of 121‒151 nm. The NLCs with the smallest size (121 nm) showed greater adipocyte internalization and differentiation prevention than the larger size. The small-sized NLCs promoted CLA delivery into adipocytes by 5.5-fold as compared to free control. The nanocarriers reduced fat accumulation in adipocytes by counteracting the expression of the adipogenic transcription factors peroxisome proliferator activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α, and lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Localized administration of CLA-loaded tocol NLCs significantly reduced body weight, total cholesterol, and liver damage indicators in obese rats. The biodistribution study demonstrated that the nanoparticles mainly accumulated in liver and adipose tissues. The NLCs decreased adipocyte hypertrophy and cytokine overexpression in the groin and epididymis to a greater degree than the combination of free α-tocopherol and CLA. In conclusion, the lipid-based nanocarriers were verified to inhibit adipogenesis in an efficient and safe way.

Conjugated linoleic acid (CLA) reduces HFD-induced obesity by enhancing BAT thermogenesis and iWAT browning via the CD36-AMPK pathway.

The antiobesity effect of conjugated linoleic acid (CLA) has been reported. However, the underlying mechanisms have not been fully clarified. Thus, this study aimed to investigate the effects of CLA on thermogenesis of interscapular brown adipose tissue (iBAT) and browning of inguinal subcutaneous white adipose tissue (iWAT) and explore the possible signaling pathway. The in vivo results showed that CLA enhanced the O2 consumption and heat production in HFD (high-fat diet)-fed female mice by roughly 38%. Meanwhile, CLA increased the average iBAT temperature by 2°C at the room temperature and cold exposure, respectively. Correspondingly, CLA caused 1.6- and 2.4-fold increases in the expression of UCP1 (uncoupling protein 1) of BAT and iWAT, respectively, suggesting the activated iBAT thermogenesis and iWAT browning in HFD-fed female mice. Meanwhile, CLA could promote the formation of brown and beige adipocytes in differentiated stromal vascular cells (SVCs) isolated from iBAT and iWAT (the expressions of UCP1 were promoted by about twofold changes). In possible mechanisms, CLA stimulated the expression of CD36 and the activation of the AMPK pathway in mice iBAT and iWAT as well as the differentiated SVCs. However, inhibition of CD36 and AMPK (adenosine 5'-monophosphate-activated protein kinase) abolished the promotive effects of CLA on brown and beige adipocytes formation. Hence, we showed that CLA reduced HFD-induced obesity through enhancing iBAT thermogenesis and iWAT browning via the  CD36-AMPK pathway.

Conjugated Linoleic Acid Ameliorates Hydrogen Peroxide-Induced Mitophagy and Inflammation via the DRP1-mtDNA-STING Pathway in Bovine Hepatocytes.

Oxidative stress is tightly associated with liver dysfunction and injury in dairy cows. Previous studies have shown that cis-9, trans-11 conjugated linoleic acid (CLA) possesses anti-inflammatory and antioxidative abilities. In this study, the bovine hepatocytes were pretreated with CLA for 6 h, followed by treatment with hydrogen peroxide (H2O2) for another 6 h to investigate the antioxidative effect of CLA and uncover the underlying mechanisms. The results demonstrated that H2O2 treatment elevated the level of mitophagy, promoted mitochondrial DNA (mtDNA) leakage into the cytosol, and activated the stimulator of interferon genes (STING)/nuclear factor kappa B (NF-κB) signaling pathway to trigger an inflammatory response in bovine hepatocytes. In addition, the dynamin-related protein 1(DRP1)-mtDNA-STING-NF-κB axis contributed to the H2O2-induced oxidative injury of bovine hepatocytes. CLA could reduce mitophagy and the inflammatory response to attenuate oxidative damage via the DRP1/mtDNA/STING pathway in bovine hepatocytes. These findings offer a theoretical foundation for the hepatoprotective effect of CLA against oxidative injury in dairy cows.

Dietary conjugated linoleic acid downregulates the AlCl3-induced hyperactivation of compensatory and maladaptive signalling in the mouse brain cortex.

Oxidative stress, hyperactivation of compensatory mechanisms (unfolded protein response, UPR; nuclear factor erythroid 2-related factor 2, Nrf2) and the stimulation of maladaptive response (inflammation/apoptosis) are interconnected pathogenic processes occurring during Alzheimer's disease (AD) progression. The neuroprotective ability of dietary Conjugated linoleic acid (CLAmix) in a mouse model of AlCl3-induced AD was recently described but, the effects of AlCl3 or CLAmix intake on these pathogenic processes are still unknown. The effects of dietary AlCl3 or CLAmix - alone and in combination - were examined in the brain cortex of twenty-eight BalbC mice divided into 4 groups (n = 7 each). The neurotoxic effects of AlCl3 were investigated in animals treated for 5 weeks with 100 mg/kg/day (AL). CLAmix supplementation (600 mg/kg bw/day) for 7 weeks (CLA) was aimed at evaluating its modulatory effects on the Nrf2 pathway while its co-treatment with AlCl3 during the last 5 weeks of CLAmix intake (CLA + AL) was used to investigate its neuroprotective ability. Untreated mice were used as controls. In the CLA group, the NADPH oxidase (NOX) activation in the brain cortex was accompanied by the modulation of the Nrf2 pathway. By contrast, in the AL mice, the significant upregulation of oxidative stress markers, compensatory pathways (UPR/Nrf2), proinflammatory cytokines (IL-6, TNFα) and the proapoptotic protein Bax levels were found as compared with control. Notably, in CLA + AL mice, the marked decrease of oxidative stress, UPR/Nrf2 markers and proinflammatory cytokines levels were associated with the significant increase of the antiapoptotic protein Bcl2. The involvement of NOX in the adaptive response elicited by CLAmix along with its protective effects against the onset of several pathogenic processes triggered by AlCl3, broadens the knowledge of the mechanism underlying the pleiotropic activity of Nrf2 activators and sheds new light on their potential therapeutic use against neurodegenerative disorders.

Conjugated Linoleic Acid Reduces Lipid Accumulation via Down-regulation Expression of Lipogenic Genes and Up-regulation of Apoptotic Genes in Grass Carp (Ctenopharyngodon idella) Adipocyte In Vitro.

The relationship between conjugated linoleic acid (CLA) and lipogenesis has been extensively studied in mammals and some cell lines, but it is relatively rare in fish, and the potential mechanism of action of CLA reducing fat mass remains unclear. The established primary culture model for studying lipogenesis in grass carp (Ctenopharyngodon idella) preadipocytes was used in the present study, and the objective was to explore the effects of CLA on intracellular lipid and TG content, fatty acid composition, and mRNA levels of adipogenesis transcription factors, lipase, and apoptosis genes in grass carp adipocytes in vitro. The results showed that CLA reduced the size of adipocyte and lipid droplet and decreased the content of intracellular lipid and TG, which was accompanied by a significant down-regulation of mRNA abundance in transcriptional regulators including peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, sterol regulatory element-binding protein (SREBP) 1c, lipase genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL). Meanwhile, it decreased the content of saturated fatty acids (SFAs) and n - 6 polyunsaturated fatty acid (n-6 PUFA) and increased the content of monounsaturated fatty acid (MUFA) and n - 3 polyunsaturated fatty acid (n-3 PUFA) in primary grass carp adipocyte. In addition, CLA induced adipocyte apoptosis through downregulated anti-apoptotic gene B-cell CLL/lymphoma 2 (Bcl-2) mRNA level and up-regulated pro-apoptotic genes tumor necrosis factor-α (TNF-α), Bcl-2-associated X protein (Bax), Caspase-3, and Caspase-9 mRNA level in a dose-dependent manner. These findings suggest that CLA can act on grass carp adipocytes through various pathways, including decreasing adipocyte size, altering fatty acid composition, inhibiting adipocyte differentiation, promoting adipocyte apoptosis, and ultimately decreasing lipid accumulation.

Lithium Chloride Promotes Endogenous Synthesis of CLA in Bovine Mammary Epithelial Cells.

Although conjugated linoleic acid (CLA) can promote human health, its content in milk is insufficient to have a significant impact. The majority of the CLA in milk is produced endogenously by the mammary gland. However, research on improving its content through nutrient-induced endogenous synthesis is relatively scarce. Previous research found that the key enzyme, stearoyl-CoA desaturase (SCD) for the synthesis of CLA, can be expressed more actively in bovine mammary epithelial cells (MAC-T) when lithium chloride (LiCl) is present. This study investigated whether LiCl can encourage CLA synthesis in MAC-T cells. The results showed that LiCl effectively increased SCD and proteasome α5 subunit (PSMA5) protein expression in MAC-T cells as well as the content of CLA and its endogenous synthesis index. LiCl enhanced the expression of proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), and its downstream enzymes acetyl CoA carboxylase (ACC), fatty acid synthase (FASN), lipoprotein lipase (LPL), and Perilipin 2 (PLIN2). The addition of LiCl significantly enhanced p-GSK-3ß, ß-catenin, p-ß-catenin protein expression, hypoxia-inducible factor-1α (HIF-1α), and downregulation factor genes for mRNA expression (P < 0.05). These findings highlight that LiCl can increase the expression of SCD and PSMA5 by activating the transcription of HIF-1α, Wnt/ß-catenin, and the SREBP1 signaling pathways to promote the conversion of trans-vaccenic acid (TVA) to the endogenous synthesis of CLA. This data suggests that the exogenous addition of nutrients can increase CLA content in milk through pertinent signaling pathways.

Encapsulation of conjugated linoleic acid and ruminant trans fatty acids to study the prevention of metabolic syndrome-a review.

Studies have reported the potential benefits of consuming conjugated linoleic acid (CLA) and ruminant trans fatty acids (R-TFAs) in reducing the risk factors of metabolic syndrome (MetS). In addition, encapsulation of CLA and R-TFAs may improve their oral delivery and further decrease the risk factors of MetS. The objectives of this review were (1) to discuss the advantages of encapsulation; (2) to compare the materials and techniques used for encapsulating CLA and R-TFAs; and (3) to review the effects of encapsulated vs non-encapsulated CLA and R-TFAs on MetS risk factors. Examination of papers citing micro- and nano-encapsulation methods used in food sciences, as well as the effects of encapsulated vs non-encapsulated CLA and R-TFAs, was conducted using the PubMed database. A total of 84 papers were examined; of these, 18 studies were selected that contained information on the effects of encapsulated CLA and R-TFAs. The 18 studies that described encapsulation of CLA or R-TFAs indicated that micro- or nano-encapsulation processes stabilized CLA and prevented oxidation. CLA was mainly encapsulated using carbohydrates or proteins. So far, oil-in-water emulsification followed by spray-drying were the frequently used techniques for encapsulation of CLA. Further, 4 studies investigated the effects of encapsulated CLA on MetS risk factors compared with non-encapsulated CLA. A limited number of studies investigated the encapsulation of R-TFAs. The effects of encapsulated CLA or R-TFAs on the risk factors for MetS remain understudied; thus, additional studies comparing the effects of encapsulated and non-encapsulated CLA or R-TFAs are needed.

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.

Effect of nitro-conjugated linoleic acid on the inflammatory response of murine macrophages activated with lipopolysaccharide derived from Prevotella intermedia.

Nitro-conjugated linoleic acid (NO2-CLA) has been observed to manifest salutary signaling responses, including anti-inflammatory and antioxidant properties. Here, the authors have explored the influence and underlying mechanisms of NO2-CLA on the proinflammatory reaction of murine macrophages that were challenged with lipopolysaccharide (LPS) derived from Prevotella intermedia, a putative periodontopathic bacterium. Treatment of LPS-activated RAW264.7 cells with NO2-CLA notably dampened the secretion of iNOS-derived NO, IL-1ß and IL-6 as well as their gene expressions and significantly enhanced the markers for M2 macrophage polarization. NO2-CLA promoted the HO-1 expression in cells challenged with LPS, and tin protoporphyrin IX, an HO-1 inhibitor, significantly reversed the NO2-CLA-mediated attenuation of NO secretion, but not IL-1ß or IL-6. We found that cells treated with NO2-CLA significantly increased mRNA expression of PPAR-γ compared to control cells, and NO2-CLA significantly reverted the decrease in PPAR-γ mRNA caused by LPS. Nonetheless, antagonists to PPAR-γ were unable to reverse the NO2-CLA-mediated suppression of inflammatory mediators. In addition, NO2-CLA did not alter the p38 and JNK activation elicited by LPS. Both NF-κB reporter activity and IκB-α degradation caused by LPS were notably diminished by NO2-CLA. NO2-CLA was observed to interrupt the nuclear translocation and DNA binding of p50 subunits caused by LPS with no obvious alterations in p65 subunits. Further, NO2-CLA attenuated the phosphorylation of STAT1/3 elicited in response to LPS. We propose that NO2-CLA could be considered as a possible strategy for the therapy of periodontal disease, although additional researches are certainly required to confirm this.

Cellular and humoral immunity of broilers subjected to posthatch fasting and a prestarter diet containing conjugated linoleic acid.

This study aimed to evaluate the immunity of chickens up to 35 d subjected to posthatch fasting and supplementation with conjugated linoleic acid (CLA). A total of 320 chicks were housed in a completely randomized design with a 2 × 2 factorial arrangement (0 or 12 h of fasting × 0.000 or 0.025% CLA in a prestarter diet), totaling 4 treatments (No-F-12 h; F-12 h; No-CLA; CLA) with 8 replicates of 10 birds each. The relative weights (% body weight) of the spleen and bursa were determined 12 h posthatch (Post-12 h) and then weekly. Immunoglobulin Y (IgY) titers against Newcastle disease virus (NDV) were measured by ELISA in the yolk sac contents Post-12 h and in the serum weekly. Hypersensitivity to phytohemagglutinin (PHA) inoculation was evaluated by toe-web swelling response on d 13 and 34, 4 times a day (after 3 h, 6 h, 12 h, and 24 h inoculation, respectively, PHA-3 h, PHA-6 h, PHA-12 h, and PHA-24 h). The data were subjected to analysis of variance (P < 0.05). F-12h reduced the Post-12 h relative weight of the spleen, and CLA reduced the relative weight of the bursa at this stage and at 28 d. At 13 d, F-12 h reduced PHA-3 h, whereas PHA-12 h was increased by CLA. At 34 d, CLA reduced PHA-3 h. A greater reaction was observed in the No-F-12 h-CLA chicks, for the PHA-24 h. In the Post-12 h evaluation, F-12h reduced, whereas CLA increased NDV-specific IgY titers in the yolk sac. No-F-12 h-No-CLA chicks had the lowest serum titers. At 21 d, F-12 h-CLA chicks exhibited the highest serum titers. Titers were higher in the F-12 h-No-CLA chicks, when compared to other treatments. At 28 d, fasting reduced the titers. In conclusion, F-12 h and CLA accelerated the transfer of immunoglobulins from the yolk sac to the serum. F-12 h impairs cellular immunity, whereas CLA favors it.

The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose-response meta-analysis.

BACKGROUND: The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines, cytokines, malondialdehyde (MDA) and liver function enzymes in patients at risk of cardiovascular disease. METHODS: Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods. RESULTS: A pooled analysis of 13 randomized controlled trials (RCTs) revealed that CLA supplementation led to a significant increment in fasting blood glucose (FBG) (WMD: 4.49 mg/dL; 95%CI: 2.39 to 6.59; P < 0.001), and aspartate aminotransferase (AST) (WMD: 2.54 IU/L; 95%CI: 0.06 to 5.01; P = 0.044). Moreover, CLA supplementation decreased leptin (WMD: -1.69 ng/ml; 95% CI: -1.80 to -1.58; P < 0.001), and interleukin 6 (IL-6) (WMD: -0.44 pg/ml; 95%CI: -0.86 to -0.02; P = 0.037). However, there was no effect on hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and alanine aminotransferase (ALT) adiponectin compared to the control group. CONCLUSION: Our findings showed the overall favorable effect of CLA supplementation on the adipokines and cytokines including serum IL-6, and leptin, while increasing FBG and AST. It should be noted that the mentioned metabolic effects of CLA consumption were small and may not reach clinical importance. PROSPERO REGISTERATION COD: CRD42023426374.

The Effect of Conjugated Linoleic Acid Supplementation on Densitometric Parameters in Overweight and Obese Women-A Randomised Controlled Trial.

Background and Objectives: Conjugated linoleic acid (CLA) can improve bone health in animals, yet the effects on humans have not been consistent. Therefore, this parallel randomised controlled trial aimed to assess the effect of CLA supplementation on bone mineral density (BMD) and content (BMC) in overweight or obese women. Materials and Methods: The study population included 74 women who were divided into the CLA (n = 37) and control (n = 37) groups. The CLA group received six capsules per day containing approximately 3 g of cis-9, trans-11 and trans-10, cis-12 CLA isomers in a 50:50 ratio. The control group received the same number of placebo capsules that contained sunflower oil. BMC and BMD at total body, lumbar spine (L1-L4), and femoral neck were measured before and after a three-month intervention. Results: The comparison of BMC and BMD for the total body, lumbar spine (L1-L4), and femoral neck before and after the intervention showed no differences between the groups. However, a within-group analysis demonstrated a significant increase in BMC (p = 0.0100) and BMD (p = 0.0397) at lumbar spine (L1-L4) in the CLA group. Nevertheless, there were no significant differences between the CLA and placebo groups in changes in all analysed densitometric parameters. Conclusions: Altogether, three-month CLA supplementation in overweight and obese women did not improve bone health, although the short intervention period could have limited our findings, long-term intervention studies are needed. The study protocol was registered in the German Clinical Trials Register database (ID: DRKS00010462, date of registration: 4 May 2016).

Conjugated linoleic acid and L-carnitine combination effects on obesity-related miRNAs in diet-induced obese rats.

OBJECTIVES: Obesity is a major global health issue, resulting in significant costs and increased mortality rates. Finding effective treatments for obesity is therefore essential. This study investigated the combined effects of L-Carnitine (LC) and Conjugated Linoleic Acid (CLA) on weight loss and adipose tissue microRNA levels. SUBJECTS /METHODS: Forty male Wistar rats weighing 150-200 g and about 8 weeks old were fed either a normal fat diet (NFD) or a high-fat diet (HFD) for 8 weeks. Afterwards, the HFD group was randomly divided into four subgroups: control, LC (200 mg kg-1), CLA (500 mg kg-1), and both (n = 8 in each group). The study lasted for an additional 4 weeks. The animals' weights were recorded regularly, and after 12 weeks, miRNAs were extracted from epididymal adipose tissue and analysed using real-time PCR. The miRNA expression levels of miR-27a and miR-143 were compared between groups using Kolmogorov-Smirnov and one-way ANOVA tests in SPSS software. RESULTS: At the end of the first 8 weeks, the HFD group weighed significantly more than the NFD group. LC significantly decreased weight gain (4.2%) compared to the control group, whereas CLA alone (3.5%) or in combination with LC (3.1%) did not significantly slow weight gain. Real-time PCR results showed that the HFD group had higher miR-143 levels and lower miR-27a levels compared to the NFD group. LC and CLA increased miR-27a expression after 4 weeks, but their combination decreased miR-27a expression. CLA alone reduced miR-143 expression, whereas LC had almost no effect. Their combination also reduced miR-143 expression. CONCLUSION: CLA and LC, which are considered weight loss supplements, can potentially regulate metabolism and cellular pathways. However, their combination did not show a synergistic effect on weight loss, possibly due to the reduction in miR-27a expression. Further studies are needed to evaluate the effects of combined fat burners on obesity treatment.

Conjugated linoleic acids inhibit lipid deposition in subcutaneous adipose tissue and alter lipid profiles in serum of pigs.

Conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. However, the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition are still unclear. In this study, we explored the effects of CLAs on regulating lipid deposition in adipose tissues in terms of lipid molecules and microbiota based on a Heigai pig model. A total of 56 Heigai finishing pigs (body weight: 85.58 ±â€…10.39 kg) were randomly divided into two treatments and fed diets containing 1% soyabean oil or 1% CLAs for 40 d. CLAs reduced fat deposition and affected fatty acids composition in adipose tissues of Heigai pigs via upregulating the expression of the lipolytic gene (hormone-sensitive lipase, HSL) in vivo and in vitro. CLAs also altered the biochemical immune indexes including reduced content of total cholesterol (TChol), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) and changed lipids profiles including decreased sphingolipids especially ceramides (Cers) and sphingomyelins (SMs) in serum of Heigai pigs. Mechanically, CLAs may decrease peroxisome proliferator-activated receptorγ (PPARγ) expression and further inhibit adipogenic differentiation in adipose tissues of pigs by suppressing the function of Cers in serum. Furthermore, Pearson's correlation analysis showed HSL expression was positively related to short-chain fatty acids (SCFAs) in the gut (P ≤ 0.05) but the abundance of Cers was negatively related to the production and functions of SCFAs (P ≤ 0.05). CLAs altered the distribution of the lipid in serum and inhibited adipogenic differentiation by suppressing the function of Cers and further decreasing PPARγ expression in adipose tissues of Heigai pigs. Besides, the HSL expression and the abundance of Cers are associated with the production and functions of SCFAs in the gut.

Meat quality is affected by fat deposition and conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. We explored the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition based on a Heigai pig model. We found CLAs reduced fat deposition in vivo and in vitro and changed lipids profiles in serum including decreased sphingolipids especially cermides (Cers) and sphingomyelins in the serum of Heigai pigs. We also demonstrated CLAs inhibited adipogenic differentiation by suppressing the function of Cers and further decreasing peroxisome proliferator-activated receptorγ expression in adipose tissues. Furthermore, Pearson's correlation analysis showed hormone-sensitive lipase expression and the abundance of Cers are related to the production and functions of short-chain fatty acids in the gut. Our findings provide useful insights into the role of CLAs in regulating lipid composition in serum and lipid metabolism in adipose tissue and provide a new insight into producing high-quality pork in the pig industry by using nutritional strategies.

Transgenic mice producing the trans 10, cis 12-conjugated linoleic acid present reduced adiposity and increased thermogenesis and fibroblast growth factor 21 (FGF21).

Trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) from ruminant-derived foodstuffs can induce body fat loss after oral administration. In the current study, a transgenic mouse that produced t10c12-CLA had been generated by inserting the Propionibacterium acnes isomerase (Pai) expression cassette into the Rosa26 locus, and its male offspring were used to elucidate the enduring influence of t10c12-CLA on overall health. Compared to their wild-type (wt) C57BL/6J littermates, both biallelic Pai/Pai and monoallelic Pai/wt mice exhibited reduced plasma triglycerides levels, and Pai/wt mice exclusively showed increased serum fibroblast growth factor 21. Further analysis of Pai/Pai mice found a decrease in white fat and an increase in brown fat, with more heat release and less physical activity. Analysis of Pai/Pai brown adipose tissues revealed that hyperthermia was associated with the over-expression of carnitine palmitoyltransferase 1B, uncoupling proteins 1 and 2. These findings suggest that the systemic and long-term impact of t10c12-CLA on obesity might be mediated through the pathway of fibroblast growth factor 21 when low doses are administered or through enhanced thermogenesis of brown adipose tissues when high doses are employed.

Conjugated Linoleic Acid-Mediated Connexin-43 Remodeling and Sudden Arrhythmic Death in Myocardial Infarction.

Connexin 43 (Cx43) is expressed in the left and right ventricles and is primarily responsible for conducting physiological responses in microvasculature. Studies have demonstrated that NADPH oxidase (NOX) enzymes are essential in cardiac redox biology and are responsible for the generation of reactive oxygen species (ROS). NOX2 is linked to left ventricular remodeling following myocardial infarction (MI). It was hypothesized that conjugated linoleic acid (cLA) treatment increases NOX-2 levels in heart tissue and disrupts connexins between the myocytes in the ventricle. Data herein demonstrate that cLA treatment significantly decreases survival in a murine model of MI. The observance of cLA-induced ventricular tachyarrhythmia's (VT) led to the subsequent investigation of the underlying mechanism in this MI model. Mice were treated with cLA for 12 h, 24 h, 48 h, or 72 h to determine possible time-dependent changes in NOX and Cx43 signaling pathways in isolated left ventricles (LV) extracted from cardiac tissue. The results suggest that ROS generation, through the stimulation of NOX2 in the LV, triggers a decrease in Cx43 levels, causing dysfunction of the gap junctions following treatment with cLA. This cascade of events may initiate VT and subsequent death during MI. Taken together, individuals at risk of MI should use caution regarding cLA consumption.

Effect of sainfoin proanthocyanidins on milk fatty acids from ewes rearing suckling lambs.

Proanthocyanidins (PAC) can modulate the fatty acid (FA) profile of animal products and make them healthier for human consumption, but their effects are highly variable depending on several factors such as PAC chemical structure or dose. The present experiment aimed to evaluate the effect of PAC on the milk FA profile of Rasa Aragonesa ewes fed fresh sainfoin (PAC-containing forage legume) during the rearing period of suckling lambs (4 weeks postlambing). Twenty lactating ewes rearing a single male lamb were fed fresh sainfoin ad libitum plus 200 g/d of barley. Half the ewes were orally dosed with 100 mL of water (Sainfoin Group; n = 10) and the other half with polyethylene glycol (50 g PEG4000/100 mL water, Sainfoin + PEG Group; n = 10) to block PAC effects. Sainfoin and milk samples were collected weekly to determine their FA profile by gas chromatography. Fresh sainfoin contents of C18:3n-3 decreased from week 1 to week 2, C16:0 and C18:0 increased from week 1 to week 3, and C18:2n-6 did not change. Regarding milk FA, there were minor effects of PAC on milk-saturated FA. During the whole study, the presence of PAC increased C18:0, C18:2n-6, C18:3n-3 and total polyunsaturated FA (PUFA) n-6 and n-3, and decreased C18:1 t11, branched- and odd-chain FA. However, the decrease of milk concentrations of trans-monounsaturated FA, C18:1 t10, and total conjugated linoleic acid (CLA) and the increase of total PUFA due to the presence of PAC occurred only in week 1, while CLA c9,t11 was lower during weeks 1 and 2. The canonical analyses confirmed the differences between treatments in the FA profile of milk. Overall, the use of fresh sainfoin in the diet of lactating ewes resulted in a beneficial modification of the concentration of several milk FAs, suggesting some changes in ruminal biohydrogenation.