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

Background and aimsConjugated 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 resultsIn 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.ConclusionsIn Chinese adults with elevated body fat percentage, 3.2 g/day CLA supplementation may be effective in preserving MM, especially in the trunk region.RegistrationThis study was registered at ClinicalTrials.gov as NCT03915808 on April 9, 2019.     

Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms

Neuroendocrine tumours (NETs) represent a heterogeneous family of neoplasms, which may develop from different endocrine glands (such as the pituitary, the parathyroid or the neuroendocrine adrenal glands), endocrine islets (within the thyroid or pancreas) as well as from endocrine cells dispersed between exocrine cells throughout the digestive and respiratory tracts. The development of somatostatin analogues (SSA) as important diagnostic and treatment tools has revolutionised the clinical management of patients with NETs. However, although symptomatic relief and stabilisation of tumour growth for various periods of time are observed in many patients treated with SSA, tumour regression is rare. Possible mechanisms when this does occur include antagonism of local growth factor release and effects, probably including activation of tyrosine and serine-threonine phosphatases, and indirect effects via anti-angiogenesis. The development of new SSA, new drug combination therapies and chimaeric molecules should further improve the clinical management of these patients, as should a more complete understanding of their mode of action.     

Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue

Conjugated linoleic acid (CLA) is a unique lipid that elicits dramatic reductions in adiposity in several animal models when included at < or = 1% of the diet. Despite a flurry of investigations, the precise mechanisms by which conjugated linoleic acid elicits its dramatic effects in adipose tissue and liver are still largely unknown. In vivo and in vitro analyses of physiological modifications imparted by conjugated linoleic acid on protein and gene expression suggest that conjugated linoleic acid exerts its de-lipidating effects by modulating energy expenditure, apoptosis, fatty acid oxidation, lipolysis, stromal vascular cell differentiation and lipogenesis. The purpose of this review shall be to examine the recent advances and insights into conjugated linoleic acid's effects on obesity and lipid metabolism, specifically focused on changes in gene expression and physiology of liver and adipose tissue.     

Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane-pretreated rats with long-term feeding of diet containing beef tallow

Background

We have indicated previously that long-term feeding of beef tallow increases colorectal cancer in rats. In this study, we investigated the effects of conjugated linoleic acid (CLA) on colon carcinogenesis in rats under long-term feeding of beef tallow diets, pretreated with azoxymethane (AOM).

Methods

Six-week-old male Sprague–Dawley rats were fed with 10% beef tallow diet only, 10% beef tallow with 1% CLA in triglyceride form (CLA-TG), or 10% beef tallow with 1% CLA in free fatty acid form (CLA-FFA). Colon carcinogenesis was induced by two intraperitoneal injections of AOM. Aberrant crypt foci (ACFs) were examined at 12 weeks. Cancer, cell proliferation, apoptosis, Wnt signaling, and the arachidonic acid cascade were examined at 44 weeks.

Results

At 12 weeks, CLA-TG and CLA-FFA attenuated the increase in ACFs induced by 10% beef tallow and AOM pretreatment. At 44 weeks, both forms of CLA attenuated multiple colon cancers, and CLA-FFA reduced the incidence of colon cancer to 50% of that seen with CLA-TG. CLA-TG and CLA-FFA decreased the number of 5-bromo-2′-deoxyuridine-positive cells in AOM-pretreated rats fed with 10% beef tallow. CLA-FFA increased the number of apoptotic cells and the activity of caspase-3 in the colon mucosa, and CLA-TG enhanced the activity of caspase-3. Both forms of CLA suppressed Wnt signaling and the arachidonic acid cascade in rats treated with beef tallow and AOM.

Conclusion

These results suggested that CLA-TG and CLA-FFA suppressed colon carcinogenesis in rats with long-term feeding of a 10% beef tallow diet, through several mechanisms. The results of the present study with rats might be applicable to humans.     

Dietary oxidized linoleic acid lowers triglycerides via APOA5/APOClll dependent mechanisms

Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) and that atherosclerosis is increased when animals are fed a high cholesterol diet in the presence of oxidized linoleic acid. Interestingly, we found that in the absence of dietary cholesterol, the oxidized fatty acid fed low-density lipoprotein (LDL) receptor negative mice appeared to have lower plasma triglyceride (TG) levels as compared to animals fed oleic acid. In the present study, we fed C57BL6 mice a normal mice diet supplemented with oleic acid or oxidized linoleic acid (at 18 mg/animal/day) for 2 weeks. After the mice were sacrificed, we measured the plasma lipids and collected livers for the isolation of RNA. The results showed that while there were no significant changes in the levels of total cholesterol and high-density lipoprotein cholesterol (HDLc), there was a significant decrease (41.14%) in the levels of plasma TG in the mice that were fed oxidized fatty acids.The decreases in plasma TG levels were accompanied by significant increases (P < 0.001) in the expressions of APOA5 and acetyl-CoA oxidase genes as well as a significant (P < 0.04) decrease in APOClll gene expression. Oxidized lipids have been suggested to be ligands for peroxisome proliferator-activated receptor (PPARα). However, there were no increases in the mRNA or protein levels of PPARα in the oxidized linoleic acid fed animals. These results suggest that oxidized fatty acids may act through an APOA5/APOClll mechanism that contributes to lowering of TG levels other than PPARα induction.     

Peroxidised linoleic acid and experimental pancreatitis

High concentrations of lipid peroxidation (free-radical oxidation) products have been found in bile from patients with recurrent pancreatitis, and the principal component, after hydrolysis, has been identified as an isomerised form of linoleic acid -- typical concentration 25 mmol/l, compared with 4 mmol/l in controls. Chromatographically identical products can be generated by peroxidising linoleic acid using an ultraviolet (UV) source in the presence of albumin, whereas peroxidation by lipoxidase without albumin results in a constellation of products that bear no resemblance to those in biological fluids. These facts, and the suspicion that reflux of abnormal bile may be an initiating mechanism in acute pancreatitis, led us to investigate the effects of linoleic acid peroxidation products in the rat pancreas. Two concentrations of ultraviolet-peroxidised linoleic acid were used (3.6 mmol/l or 25 mmol/l, in a 2.09% solution of bile salts containing albumin 10 g/l) to simulate the human findings and, for comparison, the effects of lipoxidase-peroxidised linoleic acid, 25 mmol/l (in the 2.09% bile salt solution but without albumin), were also studied. 100 microliter of test solution was infused retrogradely into the pancreatic duct using a syringe pump. The results were assessed microscopically at 3-h intervals, and histologically at 12 h: if the animal died before the end of the experiment, the time of death was recorded. Both forms of peroxidised linoleic acid, 25 mmol/l, caused a greater degree of pancreatic injury than that produced by bile salts alone (e.g., macroscopic score at 3 h: ultraviolet, P less than 0.001; lipoxidase, P less than 0.05). Non-peroxidised linoleic acid 25 mmol/l caused less damage than ultraviolet-peroxidised linoleic acid 25 mmol/l, both macroscopically (3 h: P less than 0.01; 12 h: P less than 0.05) and on histology (P less than 0.01). Pancreatic haemorrhage was not a feature.     

Peroxidised linoleic acid and experimental pancreatitis

Summary High concentrations of lipid peroxidation (free-radical oxidation) products have been found in bile from patients with recurrent pancreatitis, and the principal component, after hydrolysis, has been identified as an isomerised form of linoleic acid —typical concentration 25 mmol/l, compared with 4 mmol/l in controls. Chromatographically identical products can be generated by peroxidising linoleic acid using an ultraviolet (UV) source in the presence of albumin, whereas peroxidation by lipoxidase without albumin results in a constellation of products that bear no resemblance to those in biological fluids. These facts, and the suspicion that reflux of abnormal bile may be an initiating mechanism in acute pancreatitis, led us to investigate the effects of linoleic acid peroxidation products in the rat pancreas. Two concentrations of ultraviolet-peroxidised linoleic acid were used (3.6 mmol/l or 25 mmol/l, in a 2.09% solution of bile salts containing albumin 10 g/l) to simulate the human findings and, for comparison, the effects of lipoxidase-peroxidised linoleic acid, 25 mmol/l (in the 2.09% bile salt solution but without albumin), were also studied. 100 μl of test solution was infused retrogradely into the pancreatic duct using a syringe pump. The results were assessed microscopically at 3-h intervals, and histologically at 12 h: if the animal died before the end of the experiment, the time of death was recorded. Both forms of peroxidised linoleic acid, 25 mmol/l, caused a greater degree of pancreatic injury than that produced by bile salts alone (e.g., macroscopic score at 3 h: ultraviolet,P<0.01; lipoxidase,P<0.05). Non-peroxidised linoleic acid 25 mmol/l caused less damage than ultraviolet-peroxidised linoleic acid 25 mmol/l, both macroscopically (3 h:P<0.01; 12 h:P<0.05) and on histology (P<0.01). Pancreatic haemorrhage was not a feature. An abstract of this work was presented at the meeting of the Pancreatic Society of Great Britain and Ireland held at Manchester in November 1983 (Gut 1984; 25: 693).     

Dietary linoleic acid, gastric acid, and prostaglandin secretion

Basal and pentagastrin-stimulated gastric acid secretion, fasting serum gastrin concentrations, and the gastric output of prostaglandin E and its major metabolite 13,14-dihydro 15-keto prostaglandin E2 were measured in 9 normal subjects before and after 14-20 days of dietary supplementation with linoleic acid. Mean maximal gastric acid output fell from 36.0 +/- 3.3 (SEM) to 30.1 +/- 2.9 mmol/h (p less than 0.05), although mean basal acid output was not significantly affected (8.3 +/- 2.1 and 7.2 +/- 1.7 mmol/h, respectively). Mean fasting serum gastrin concentrations increased from 19.2 +/- 3.1 to 30.9 +/- 3.8 ng/L (p less than 0.01) after linoleic acid, probably because of acid suppression. The mean output of prostaglandin E increased from 498 +/- 110 to 1254 +/- 465 ng/h (p less than 0.05); that of its metabolite increased from 165 +/- 18 to 1168 +/- 645 ng/h (p less than 0.01). These findings show that in normal subjects essential fatty acid weakly inhibits gastric acid secretion, but considerably increases gastric prostaglandin output.     

碘化亚油酸及5-氟尿嘧啶酯抑制肝细胞癌生长的初步研究

目的 合成并评价碘化亚油酸(ILA)、碘化亚油酸5-氟尿嘧啶核苷偶联酯(IFU)在体内外对肝细胞癌的抑制作用.方法 ILA和IFU均通过化学合成及纯化,并经1H核磁谱证实.用不同浓度的ILA、IFU、5-氟尿嘧啶(5-FU)和传统碘油分别处理两株人肝癌细胞:SMMC-7721和QGY-7703,检测72 h细胞存活率,并计算50％抑制浓度(IC50)和90％抑制浓度(ICg0).经SMMC-7721肝癌细胞皮下接种成功的30只裸鼠随机分成5组:ILA组、IFU组、5-FU组、传统碘油组和二甲基亚砜(DMSO)组(对照组),并分别1次瘤内注射100μ1的ILA、IFU、5-FU、传统碘油和DMSO,4周后计算抑瘤率.组间比较用t检验. 结果 对SMMC-7721细胞,ILA、IFU和5-FU的IC50分别为134.38 μ mol/L、17.55 μ mol/L、7.38μmol/L;IC90分别为192.88 μmol/L、97.63 μmol/L、大于200μmol/L.对QGY-7703细胞,ILA、IFU和5-FU的IC50分别为109.55μmol/L、44.79μmol/L、98.06 μmol/L; IC90三者均大于200μmol/L.对SMMC-7721和QGY-7703细胞,传统碘油IC50均大于400μmol/L.与DMSO对照组抑瘤率0比较,ILA组、IFU组和5-FU组的抑瘤率分别为31.90％、56.90％、31.04％,统计值t分别为2.37、4.91、2.59,P值均小于0.05,差异均有统计学意义.而IFU组抑瘤率高于ILA组和5-FU组,传统碘油组抑瘤率为0.87％,未见抑瘤活性.结论 ILA和IFU均可在体内、外抑制肝癌细胞增殖,并且IFU的抑瘤作用强于ILA.     

Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial

BACKGROUND: Abdominal obesity is strongly related to metabolic disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans have not yet been tested. OBJECTIVE: To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic disorders. METHODS: Twenty-five abdominally obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass index (BMI), 32+/-2.7 kg/m(2) (mean+/-s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men received a placebo. The main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids, glucose and insulin. RESULTS: At baseline, there were no significant differences between groups in anthropometric or metabolic variables. After 4 weeks there was a significant decrease in SAD (cm) in the CLA group compared to placebo (P=0.04, 95% CI; -1.12, -0.02). Other measurements of anthropometry or metabolism showed no significant differences between the groups. CONCLUSIONS: These results indicate that CLA supplementation for 4 weeks in obese men with the metabolic syndrome may decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be further investigated in larger trials with longer duration.     

Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by benzo （a） pyrene and chemopreventive mechanisms

AIM: To explore the inhibition of conjugated linoleic acidisomers in different purity (75 % purity c9,t11-, 98 % purityc9,t11- and 98 % purity t10,c12-CLA) on the formation offorestomach neoplasm and cheopreventive mechanisms.METHODS: Forestomach neoplasm model induced by B(a)P in KunMing mice was established. The numbers of tumorand diameter of each tumor in forestomach were counted;the mice plasma malondialdehyde (MDA) were measuredby TBARS assay; TUNEL assay was used to analyze theapoptosis in forestomach neoplasia and the expression ofMEK-1, ERK-1, MKP-1 protein in forestomach neoplasm werestudied by Western Blotting assay.RESULTS: The incidence of neoplasm in B(a)P group, 75 %purity c9, t11-CLA group, 98 % purity cg,t11-CLA groupand 98 % purity t10, c12-CLA group was 100 %, 75.0 %(P＞0.05), 69.2 % (P＜0.05) and 53.8 % (P＜0.05) respectivelyand the effect of two CLA isomers in 98 % purity onforestomach neoplasia was significant; CLA showed noinfluence on the average tumor numbers in tumor-bearingmouse, but significantly decreased the tumor size, the tumoraverage diameter of mice in 75 % purity c9,t11-CLA group,98 % purity cg,t11-CLA group and 98 % purity t10, c12-CLAgroup was 0.157±0.047 cm, 0.127±0.038 cm and 0.128±0.077 cm (P＜0.05) and 0.216±0.088 cm in B(a)P group;CLA could also significantly increase the apoptosis cellnumbers by 144.00±20.31, 153.75±23.25, 157.25±15.95(P＜0.05) in 75 % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10,c12-CLA group (30.88±3.72 in BP group); but there were no significant differencesbetween the effects of 75 % purity c9,t11-CLA and twoisomers in 98 % purity on tumor size and apoptotic cellnumbers; the plasma levels of MDA in were increased by75 % purity c9,t11-ClA, 98 % purity c9,t11-CLA and 98 %purity t10,c12-CLA. The 75 % purity c9,t11-CLA showedstronger inhibition; CLA could also inhibit the expression ofERK-1 protein and promote the expression of MKP-1 protein,however no influence of CLA on MEK-1 protein was observed.CONCLUSION: Two isomers in 98 % purity show strongerinhibition on carcinogenesis. However, the inhibitorymechanisms of CLA on carcinogenesis is complicated, whichmay be due to the increased mice plasmaMDA, the inducingapoptosis in tumor tissues. And the effect of CLA on theexpression of ERK-1 and MKP-1 may be one of themechanisms of the inhibition of CLA on the tumor.     

Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma

In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma(EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett's esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the refluxBarrett's-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite byincreasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett's cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits.     

Alcohol, metabolic syndrome and obesity: impact on treatment efficacy

Among environmental factors, alcohol consumption and metabolic syndrome should play a major role on the response to treatment in chronic hepatitis C. In a prospective study, regular alcohol consumption (1 drink/d) within 6 months prior to bi-therapy in patients with chronic hepatitis C was significantly associated with treatment stop, underlining the need for specific and multidisciplinary management of those patients. Metabolic steatosis and overall the degree of insulin resistance assessed by HOMA index, also seem to have negative impact on sustained virological response to treatment. The high prevalence of insulin resistance in chronic hepatitis C warrant performing metabolic investigations before to start antiviral treatment. Efficacy of insulin sensitizing agents on virological response in patients treated with bi-therapy is under investigation in randomized controlled trials.