The Lipid-Heart Hypothesis and the Keys Equation Defined the Dietary Guidelines but Ignored the Impact of Trans-Fat and High Linoleic Acid Consumption.

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (ΔChol.) from the consumption of saturated fat (ΔS), polyunsaturated fat (ΔP), and cholesterol (ΔZ): ΔChol. = 1.2(2ΔS - ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

Protective effect of linoleic acid on liver toxicity induced by methotrexate / Efecto protector del ácido linoleico sobre la toxicidad hepática inducida por metotrexato

SUMMARY: We aimed to investigate the protective effect of linoleic acid on liver toxicity induced by methotrexate. The study was carried out in partnership with the Department of Anatomy and Department of Medical Pharmacology of Çukurova University Faculty of Medicine, using the laboratory facilities of the Department of Medical Pharmacology. Human hepatocyte cell line (CRL- 11233) cells obtained from the American Type Culture Collection Organization (ATCC) were used. Expressions of apoptotic pathway markers, apoptosis inducing factor (AIF), BAX, BCL 2, GADD 153, 78-kDa glucose-regulated protein (GRP78), and CASPASE-3 were evaluated. All analyzes were examined in four groups (Group 1; control, Group 2; linoleic acid given, Group 3; methotrexate given and Group 4; linoleic acid and methotrexate given). The mean ± standard error values of the obtained results as nanogram / milliliter (ng / ml) are in Group I, Group II, Group III and Group IV, respectively; AIF values, 0.4150 ± 0.1208, 0.3633 ± 0.2389, 1.792 ± 0.3611 and 1.077 ± 0.1646, BAX values, 0.900 ± 0.1864, 1.002 ± 0.2098, 8.352 ± 1.467 and 4.295 ± 1.522, BCL 2 values, 13.93 ± 1.198, 13.92 ± 1.739, 2.938 ± 1.059 and 9.250 ± 1.492, GADD 153, 0.7333 ± 0.1751, 0.7067 ± 0.2115, 1.650 ± 0.2950 and 1.237 ± 0.1805, GRP78, 0.4767 ± 0.1804, 0.5233 ± 0.1590, 2.183 ± 0.2639 and 1.112 ± 0.2693, CASPASE-3 values , 1.127 ± 0.2033, 0.8317 ± 0.3392, 13.50 ± 1.871 and 8.183 ± 1.030. It was determined that linoleic acid has a protective effect on methotrexate-induced liver toxicity.

Nuestro objetivo fue investigar el efecto protector del ácido linoleico sobre la toxicidad hepática inducida por metotrexato. El estudio se llevó a cabo en colaboración con el Departamento de Anatomía y el Departamento de Farmacología Médica de la Facultad de Medicina de la Universidad de Çukurova, utilizando las instalaciones del laboratorio del Departamento de Farmacología Médica. Se usaron células de la línea celular de hepatocitos humanos (CRL-11233) obtenidas de la American Type Culture Collection Organisation (ATCC). Se evaluaron las expresiones de marcadores de vías apoptóticas, factor inductor de apoptosis (AIF), BAX, BCL 2, GADD 153, proteína regulada por glucosa de 78 kDa (GRP78) y CASPASE-3. Todos los análisis se examinaron en cuatro grupos (Grupo 1; control, Grupo 2; se administró ácido linoleico, Grupo 3; se administró metotrexato y Grupo 4; se administró ácido linoleico y metotrexato). Los valores medios ± error estándar de los resultados obtenidos como nanogramo/mililitro (ng/ml) se encuentran en el Grupo I, Grupo II, Grupo III y Grupo IV, respectivamente; Valores de AIF, 0,4150 ± 0,1208, 0,3633 ± 0,2389, 1,792 ± 0,3611 y 1,077 ± 0,1646, valores de Bax, 0,900 ± 0,1864, 1,002 ± 0,2098, 8,352 ± 1,467 y 4,295 ± 1,522, BCL 2 valores, 13,93 ± 1,199. 2,938 ± 1,059 y 9,250 ± 1,492, GADD 153, 0,7333 ± 0,1751, 0,7067 ± 0,2115, 1,650 ± 0,2950 y 1,237 ± 0,1805, Grp78, 0,4767 ± 0,1804, 0,5233 ± 0,1590, 2,183, ± 1,263. 1,127 ± 0,2033, 0,8317 ± 0,3392, 13,50 ± 1,871 y 8,183 ± 1,030. Se determinó que el ácido linoleico tiene un efecto protector sobre la toxicidad hepática inducida por metotrexato.

The FADS1 genotypes modify the effect of linoleic acid-enriched diet on adipose tissue inflammation via pro-inflammatory eicosanoid metabolism.

PURPOSE: Fatty acid desaturase (FADS) variants associate with fatty acid (FA) and adipose tissue (AT) metabolism and inflammation. Thus, the role of FADS1 variants in the regulation of dietary linoleic acid (LA)-induced effects on AT inflammation was investigated. METHODS: Subjects homozygotes for the TT and CC genotypes of the FADS1-rs174550 (TT, n = 25 and CC, n = 28) or -rs174547 (TT, n = 42 and CC, n = 28), were either recruited from the METabolic Syndrome In Men cohort to participate in an intervention with LA-enriched diet (FADSDIET) or from the Kuopio Obesity Surgery (KOBS) study. GC and LC-MS for plasma FA proportions and eicosanoid concentrations and AT gene expression for AT inflammatory score (AT-InSc) was determined. RESULTS: We observed a diet-genotype interaction between LA-enriched diet and AT-InSc in the FADSDIET. In the KOBS study, interleukin (IL)1 beta mRNA expression in AT was increased in subjects with the TT genotype and highest LA proportion. In the FADSDIET, n-6/LA proportions correlated positively with AT-InSc in those with the TT genotype but not with the CC genotype after LA-enriched diet. Specifically, LA- and AA-derived pro-inflammatory eicosanoids related to CYP450/sEH-pathways correlated positively with AT-InSc in those with the TT genotype, whereas in those with the CC genotype, the negative correlations between pro-inflammatory eicosanoids and AT-InSc related to COX/LOX-pathways. CONCLUSIONS: LA-enriched diet increases inflammatory AT gene expression in subjects with the TT genotype, while CC genotype could play a protective role against LA-induced AT inflammation. Overall, the FADS1 variant could modify the dietary LA-induced effects on AT inflammation through the differential biosynthesis of AA-derived eicosanoids.

Dietary Alpha-Linolenic Acid Supports High Retinal DHA Levels.

The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated optimizing retinal DHA using dietary ALA. Previous research identified 19% DHA in retinal phospholipids was associated with optimal retinal function in guinea pigs. Pregnant guinea pigs were fed dietary ALA from 2.8% to 17.3% of diet fatty acids, at a constant level of linoleic acid (LA) of 18% for the last one third of gestation and retinal DHA levels were assessed in 3-week-old offspring maintained on the same diets as their mothers. Retinal DHA increased in a linear fashion with the maximum on the diet with LA:ALA of 1:1. Feeding diets with LA:ALA of 1:1 during pregnancy and assessing retinal DHA in 3-week-old offspring was associated with optimized retinal DHA levels. We speculate that the current intakes of ALA in human diets, especially in relation to LA intakes, are inadequate to support high DHA levels in the retina.

Chronic consumption of a high linoleic acid diet during pregnancy, lactation and post-weaning period increases depression-like behavior in male, but not female offspring.

Polyunsaturated fatty acids (PUFAs) play an essential role in brain development. Emerging data have suggested a possible link between an imbalance in PUFAs and cognitive behavioral deficits in offspring. A diet rich in high linoleic acid (HLA), typically from preconception to lactation, leads to an increase in the ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids in the fetus. Arising research has suggested that a deficiency in omega-3 fatty acids is a potential risk factor for inducing autism spectrum disorder (ASD)-like behavioral deficits. However, the impact of a high n- diet during preconception, pregnancy, lactation, and post-weaning on the brain development of adolescent offspring are yet to be determined. This study examined whether consumption of an HLA diet during pregnancy, lactation, and post-weaning induced social and cognitive impairments in female and male offspring rats that resemble autistic phenotypes in humans. Female Wistar Kyoto rats were fed with either HLA or low linoleic acid (LLA) control diet for 10 weeks before mating, then continued with the same diet throughout the pregnancy and lactation period. Female and male offspring at 5 weeks old were subjected to behavioral tests to assess social interaction behavior and depression-/anxiety-like behavior. Our result showed that chronic consumption of an HLA diet did not affect sociability and social recognition memory, but induced depression-like behavior in male but not in female offspring.

Linoleic acid and the regulation of glucose homeostasis: A review of the evidence.

The consumption of linoleic acid (LA, ω-6 18:2), the most common ω-6 polyunsaturated fatty acid (PUFA) in the Modern Western diet (MWD), has significantly increased over the last century in tandem with unprecedented incidence of chronic metabolic diseases like obesity and type 2 diabetes mellitus (T2DM). Although an essential fatty acid for health, LA was a very rare fatty acid in the diet of humans during their evolution. While the intake of other dietary macronutrients (carbohydrates like fructose) has also risen, diets rich in ω-6 PUFAs have been promoted in an effort to reduce cardiovascular disease despite unclear evidence as to how increased dietary LA consumption could promote a proinflammatory state and affect glucose metabolism. Current evidence suggests that sex, genetics, environmental factors, and disease status can differentially modulate how LA influences insulin sensitivity and peripheral glucose uptake as well as insulin secretion and pancreatic beta-cell function. Therefore, the aim of this review will be to summarize recent additions to our knowledge to refine the unique physiological and pathophysiological roles of LA in the regulation of glucose homeostasis.

Sex-Specific Differences in Lysine, 3-Hydroxybutyric Acid and Acetic Acid in Offspring Exposed to Maternal and Postnatal High Linoleic Acid Diet, Independent of Diet.

BACKGROUND: Linoleic acid (LA) is an essential polyunsaturated fatty acid (PUFA) that is required for foetal growth and development. Excess intake of LA can be detrimental for metabolic health due to its pro-inflammatory properties; however, the effect of a diet high in LA on offspring metabolites is unknown. In this study, we aimed to determine the role of maternal or postnatal high linoleic acid (HLA) diet on plasma metabolites in adult offspring. METHODS: Female Wistar Kyoto (WKY) rats were fed with either low LA (LLA) or HLA diet for 10 weeks prior to conception and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), treated with either LLA or HLA diets and sacrificed at PN180. Metabolite analysis was performed in plasma samples using Nuclear Magnetic Resonance. RESULTS: Maternal and postnatal HLA diet did not alter plasma metabolites in male and female adult offspring. There was no specific clustering among different treatment groups as demonstrated by principal component analysis. Interestingly, there was clustering among male and female offspring independent of maternal and postnatal dietary intervention. Lysine was higher in female offspring, while 3-hydroxybutyric acid and acetic acid were significantly higher in male offspring. CONCLUSION: In summary, maternal or postnatal HLA diet did not alter the plasma metabolites in the adult rat offspring; however, differences in metabolites between male and female offspring occurred independently of dietary intervention.

Therapeutic delivery of siRNA with polymeric carriers to down-regulate STAT5A expression in high-risk B-cell acute lymphoblastic leukemia (B-ALL).

Overexpression and persistent activation of STAT5 play an important role in the development and progression of acute lymphoblastic leukemia (ALL), the most common pediatric cancer. Small interfering RNA (siRNA)-mediated downregulation of STAT5 represents a promising therapeutic approach for ALL to overcome the limitations of current treatment modalities such as high relapse rates and poor prognosis. However, to effectively transport siRNA molecules to target cells, development of potent carriers is of utmost importance to surpass hurdles of delivery. In this study, we investigated the use of lipopolymers as non-viral delivery systems derived from low molecular weight polyethylenimines (PEI) substituted with lauric acid (Lau), linoleic acid (LA) and stearic acid (StA) to deliver siRNA molecules to ALL cell lines and primary samples. Among the lipid-substituted polymers explored, Lau- and LA-substituted PEI displayed excellent siRNA delivery to SUP-B15 and RS4;11 cells. STAT5A gene expression was downregulated (36-92%) in SUP-B15 and (32%) in RS4;11 cells using the polymeric delivery systems, which consequently reduced cell growth and inhibited the formation of colonies in ALL cells. With regard to ALL primary cells, siRNA-mediated STAT5A gene silencing was observed in four of eight patient cells using our leading polymeric delivery system, 1.2PEI-Lau8, accompanied by the significant reduction in colony formation in three of eight patients. In both BCR-ABL positive and negative groups, three of five patients demonstrated marked cell growth inhibition in both MTT and trypan blue exclusion assays using 1.2PEI-Lau8/siRNA complexes in comparison with their control siRNA groups. Three patient samples did not show any positive results with our delivery systems. Differential therapeutic responses to siRNA therapy observed in different patients could result from variable genetic profiles and patient-to-patient variability in delivery. This study supports the potential of siRNA therapy and the designed lipopolymers as a delivery system in ALL therapy.

Nanoparticulate tablet dosage form of lisofylline-linoleic acid conjugate for type 1 diabetes: in situ single-pass intestinal perfusion (SPIP) studies and pharmacokinetics in rat.

Lisofylline (LSF) is an anti-inflammatory molecule with high aqueous solubility and rapid metabolic interconversion to its parent drug, pentoxifylline (PTX) resulting in very poor pharmacokinetic (PK) parameters, necessitating high dose and dosing frequency. In the present study, we resolved the physicochemical and pharmacokinetic limitations associated with LSF and designed its oral dosage form as a tablet for effective treatment in type 1 diabetes (T1D). Self-assembling polymeric micelles of LSF (lisofylline-linoleic acid polymeric micelles (LSF-LA PLM)) were optimized for scale-up (6 g batch size) and lyophilized followed by compression into tablets. Powder blend and tablets were evaluated as per USP. LSF-LA PLM tablet so formed was evaluated for in vitro release in simulated biological fluids (with enzymes) and for cell viability in MIN-6 cells. LSF-LA PLM in tablet formulation was further evaluated for intestinal permeability (in situ) along with LSF and LSF-LA self-assembled micelles (SM) as controls in a rat model using single-pass intestinal perfusion (SPIP) study. SPIP studies revealed 1.8-fold higher oral absorption of LSF-LA from LSF-LA PLM as compared to LSF-LA SM and ~5.9-fold higher than LSF (alone) solution. Pharmacokinetic studies of LSF-LA PLM tablet showed greater Cmax than LSF, LSF-LA, and LSF-LA PLM. Designed facile LSF-LA PLM tablet dosage form has potential for an immediate decrease in the postprandial glucose levels in patients of T1D.

Assessment of Transdermal Delivery of Topical Compounds in Skin Scarring Using a Novel Combined Approach of Raman Spectroscopy and High-Performance Liquid Chromatography.

Objective: The goal of any topical formulation is efficient transdermal delivery of its active components. However, delivery of compounds can be problematic with penetration through tough layers of fibrotic dermal scar tissue. Approach: We propose a new approach combining high-performance liquid chromatography (HPLC) and Raman spectroscopy (RS) using a topical of unknown composition against a well-known antiscar topical (as control). Results: Positive detection of compounds within the treatment topical using both techniques was validated with mass spectrometry. RS detected conformational structural changes; the 1,655/1,446 cm-1 ratio estimating collagen content significantly decreased (p < 0.05) over weeks 4, 12, and 16 compared with day 0. The amide I band, known to represent collagen and protein in skin, shifted from 1,667 to 1,656 cm-1, which may represent a change from ß-sheets in elastin to α-helices in collagen. Confirmatory elastin immunohistochemistry decreased compared with day 0, conversely the collagen I/III ratio increased in the same samples by week 12 (p < 0.05, and p < 0.0001, respectively), in keeping with normal scar formation. Optical coherence tomography attenuation coefficient representing collagen deposition was significantly decreased at week 4 compared with day 0 and increased at week 16 (p < 0.05). Innovation: This study provides a platform for further research on the simultaneous evaluation of the effects of compounds in cutaneous scarring by RS and HPLC, and identifies a role for RS in the therapeutic evaluation and theranostic management of skin scarring. Conclusions: RS can provide noninvasive information on the effects of topicals on scar pathogenesis and structural composition, validated by other analytical techniques.

Effects of Diet on Acne and Its Response to Treatment.

Our understanding of the pathogenesis of acne vulgaris is still evolving. It is known that multiple factors impact acne pathophysiology, including genetic, hormonal, inflammatory, and environmental influences. Because of its implications in many of these factors, diet has been a part of the acne discussion for decades. Several studies have evaluated the significance of the glycemic index of various foods and glycemic load in patients with acne, demonstrating individuals with acne who consume diets with a low glycemic load have reduced acne lesions compared with individuals on high glycemic load diets. Dairy has also been a focus of study regarding dietary influences on acne; whey proteins responsible for the insulinotropic effects of milk may contribute more to acne development than the actual fat or dairy content. Other studies have examined the effects of omega-3 fatty acid and γ-linoleic acid consumption in individuals with acne, showing individuals with acne benefit from diets consisting of fish and healthy oils, thereby increasing omega-3 and omega-6 fatty acid intake. Recent research into the effects of probiotic administration in individuals with acne present promising results; further study of the effects of probiotics on acne is needed to support the findings of these early studies. In this review, we discuss the current evidence regarding the diets of US patients with acne and how they may impact acne and acne treatment.

Isosorbide Di-(Linoleate/Oleate) Stimulates Prodifferentiation Gene Expression to Restore the Epidermal Barrier and Improve Skin Hydration.

The breakdown of the epidermal barrier and consequent loss of skin hydration is a feature of skin aging and eczematous dermatitis. Few treatments, however, resolve these underlying processes to provide full symptomatic relief. In this study, we evaluated isosorbide di-(linoleate/oleate) (IDL), which was generated by esterifying isosorbide with sunflower fatty acids. Topical effects of IDL in skin were compared with those of ethyl linoleate/oleate, which has previously been shown to improve skin barrier function. Both IDL and ethyl linoleate/oleate downregulated inflammatory gene expression, but IDL more effectively upregulated the expression of genes associated with keratinocyte differentiation (e.g., KRT1, GRHL2, SPRR4). Consistent with this, IDL increased the abundance of epidermal barrier proteins (FLG and involucrin) and prevented cytokine-mediated stratum corneum degradation. IDL also downregulated the expression of unhealthy skin signature genes linked to the loss of epidermal homeostasis and uniquely repressed an IFN-inducible coexpression module activated in multiple skin diseases, including psoriasis. In a double-blind, placebo-controlled trial enrolling females with dry skin, 2% IDL lotion applied over 2 weeks significantly improved skin hydration and decreased transepidermal water loss (NCT04253704). These results demonstrate mechanisms by which IDL improves skin hydration and epidermal barrier function, supporting IDL as an effective intervention for the treatment of xerotic pruritic skin.

Maternal Linoleic Acid Overconsumption Alters Offspring Gut and Adipose Tissue Homeostasis in Young but Not Older Adult Rats.

Maternal n-6 polyunsaturated fatty acids (PUFA) consumption during gestation and lactation can predispose offspring to the development of metabolic diseases such as obesity later in life. However, the mechanisms underlying the potential programming effect of n-6 PUFA upon offspring physiology are not yet all established. Herein, we investigated the effects of maternal and weaning linoleic acid (LA)-rich diet interactions on gut intestinal and adipose tissue physiology in young (3-month-old) and older (6-month-old) adult offspring. Pregnant rats were fed a control diet (2% LA) or an LA-rich diet (12% LA) during gestation and lactation. At weaning, offspring were either maintained on the maternal diet or fed the other diet for 3 or 6 months. At 3 months of age, the maternal LA-diet favored low-grade inflammation and greater adiposity, while at 6 months of age, offspring intestinal barrier function, adipose tissue physiology and hepatic conjugated linoleic acids were strongly influenced by the weaning diet. The maternal LA-diet impacted offspring cecal microbiota diversity and composition at 3 months of age, but had only few remnant effects upon cecal microbiota composition at 6 months of age. Our study suggests that perinatal exposure to high LA levels induces a differential metabolic response to weaning diet exposure in adult life. This programming effect of a maternal LA-diet may be related to the alteration of offspring gut microbiota.

N-6 Polyunsaturated Fatty Acids and Risk of Cancer: Accumulating Evidence from Prospective Studies.

Previous studies on the association between polyunsaturated fatty acids (PUFAs) and cancer have focused on n-3 PUFAs. To investigate the association between intake or blood levels of n-6 PUFAs and cancer, we searched the PubMed and Embase databases up to March 2020 and conducted a meta-analysis. A total of 70 articles were identified. High blood levels of n-6 PUFAs were associated with an 8% lower risk of all cancers (relative risk (RR) = 0.92; 95% confidence interval (CI): 0.86-0.98) compared to low blood levels of n-6 PUFAs. In the subgroup analyses by cancer site, type of n-6 PUFAs, and sex, the inverse associations were strong for breast cancer (RR = 0.87; 95% CI: 0.77-0.98), linoleic acid (LA) (RR = 0.91; 95% CI: 0.82-1.00), and women (RR = 0.88; 95% CI: 0.79-0.97). In the dose-response analysis, a 2% and 3% decrease in the risk of cancer was observed with a 5% increase in blood levels of n-6 PUFAs and LA, respectively. Thus, there was no significant association between n-6 PUFA intake and the risk of cancer. The pooled RR of cancer for the highest versus lowest category of n-6 PUFA intake was 1.02 (95% CI: 0.99-1.05). Evidence from prospective studies indicated that intake of n-6 PUFAs was not significantly associated with risk of cancer, but blood levels of n-6 PUFAs were inversely associated with risk of cancer.

Effects of plant oils with different fatty acid composition on cardiovascular risk factors in moderately hypercholesteremic Chinese adults: a randomized, double-blinded, parallel-designed trial.

OBJECTIVES: Plant oil for cooking typically provides 40% to 50% of dietary fat, 65% of linoleic acid, 44% of α-linolenic acid and 41% of oleic acid in the Chinese diet. However, the comparative effects of fatty acids derived from plant oil on cardiovascular risk factors in Chinese are still inconclusive. Hence, the aim of this study is to investigate whether cardiovascular risk factors are altered depending on various types of plant oils such as peanut oil rich in oleic acid, corn oil rich in linoleic acid, and blend oil fortified by α-linolenic acid. DESIGN: A randomized, double-blinded, parallel-designed trial. SETTING: The First and the Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. PARTICIPANTS: A total of 251 volunteers with fasting blood total cholesterol between 5.13 and 8.00 mmol L-1 were enrolled. INTERVENTION: Volunteers received peanut oil, corn oil or blend oil to use for cooking for one year. MAIN OUTCOME MEASURES: The erythrocyte membrane fatty acid composition, fasting plasma lipids, glucose and insulin concentrations and high sensitivity C-reactive protein (hsCRP) levels were measured before, during and after the intervention. The level of α-linolenic acid in erythrocyte membranes was significantly increased in the blend oil group after the intervention (P < 0.001). The level of other fatty acids did not show any statistically significant differences between the three groups. No significant differences were observed in the concentrations of fasting plasma lipids, hsCRP, glucose, and insulin among the three groups using different types of plant oils. CONCLUSIONS: The results suggest that although ingesting cooking oil with different fatty acid composition for one year could change erythrocyte membrane fatty acid compositions, it did not significantly modify cardiovascular risk factors in moderately hypercholesteremic people.

Associations of linoleic acid with markers of glucose metabolism and liver function in South African adults.

BACKGROUND: The relation between dietary and circulating linoleic acid (18:2 n-6, LA), glucose metabolism and liver function is not yet clear. Associations of dietary and circulating LA with glucose metabolism and liver function markers were investigated. METHODS: Cross-sectional analyses in 633 black South Africans (aged > 30 years, 62% female, 51% urban) without type 2 diabetes at baseline of the Prospective Urban Rural Epidemiology study. A cultural-sensitive 145-item food-frequency questionnaire was used to collect dietary data, including LA (percentage of energy; en%). Blood samples were collected to measure circulating LA (% total fatty acids (FA); plasma phospholipids), plasma glucose, glycosylated hemoglobin (HbA1c), serum gamma-glutamyl transferase (GGT), alanine (ALT) and aspartate aminotransferase (AST). Associations per 1 standard deviation (SD) and in tertiles were analyzed using multivariable regression. RESULTS: Mean (±SD) dietary and circulating LA was 6.8 (±3.1) en% and 16.0 (±3.5) % total FA, respectively. Dietary and circulating LA were not associated with plasma glucose or HbA1c (ß per 1 SD: - 0.005 to 0.010, P > 0.20). Higher dietary LA was generally associated with lower serum liver enzymes levels. One SD higher circulating LA was associated with 22% lower serum GGT (ß (95% confidence interval): - 0.25 (- 0.31, - 0.18), P < 0.001), but only ≤9% lower for ALT and AST. Circulating LA and serum GGT associations differed by alcohol use and locality. CONCLUSION: Dietary and circulating LA were inversely associated with markers of impaired liver function, but not with glucose metabolism. Alcohol use may play a role in the association between LA and liver function. TRIAL REGISTRATION: PURE North-West Province South Africa study described in this manuscript is part of the PURE study. The PURE study is registered in ClinicalTrials.gov (Identifier: NCT03225586; URL).

Consumption of Goat Cheese Naturally Rich in Omega-3 and Conjugated Linoleic Acid Improves the Cardiovascular and Inflammatory Biomarkers of Overweight and Obese Subjects: A Randomized Controlled Trial.

This study examines the value of a goat cheese naturally enriched in polyunsaturated fatty acids (PUFA) (n-3 PUFA and conjugated linolenic acid (CLA)) as means of improving cardiovascular and inflammatory health. Sixty-eight overweight and obese subjects (BMI ≥ 27 and <40 kg/m2), with at least two risk factors for cardiovascular disease (CVD) in a lipid panel blood tests, participated in a randomized, placebo-controlled, double-blind, parallel designed study. The subjects consumed for 12 weeks: (1) 60 g/d control goat cheese and (2) 60 g/d goat cheese naturally enriched in n-3 PUFA and CLA. Diet and physical activity were assessed. Anthropometric and dual-energy X-ray absorptiometry (DXA) tests were performed. Blood samples were collected at the beginning and at the end of the study period. Changes in health status, lifestyle and dietary habits, and daily compliance were recorded. The consumption of a PUFA-enriched goat cheese significantly increased plasma high-density lipoprotein (HDL)-cholesterol, as well as in apolipoprotein B, and it significantly decreased high-sensitivity C-reactive protein concentrations compared to the control goat cheese (p < 0.05). The significant improvement of the plasma lipid profile and inflammatory status of people with risk for CVD due to the consumption of PUFA-enriched cheese suggests a potential role of this dairy product as an alternative to develop high nutritional value food in a balanced diet comprising regular exercise.

Decreasing the Ratio of Dietary Linoleic to α-Linolenic Acid from 10 to 4 by Changing Only the Former Does Not Prevent Adiposity or Bone Deterioration in Obese Mice.

BACKGROUND: Linoleic acid (LA; 18:2n-6) has been considered to promote low-grade chronic inflammation and adiposity. Studies show adiposity and inflammation are inversely associated with bone mass. OBJECTIVES: This study tested the hypothesis that decreasing the dietary ratio of LA to α-linolenic acid (ALA, 18:3n-3), while keeping ALA constant, mitigates high-fat diet (HF)-induced adiposity and bone loss. METHODS: Male C57BL/6 mice at 6 wk old were assigned to 4 treatment groups and fed 1 of the following diets ad libitum for 6 mo: a normal-fat diet (NF; 3.85 kcal/g and 10% energy as fat) with the ratio of the PUFAs LA to ALA at 6; or HFs (4.73 kcal/g and 45% energy as fat) with the ratio of LA to ALA at 10:1, 7:1, or 4:1, respectively. ALA content in the diets was kept the same for all groups at 1% energy. Bone structure, body composition, bone-related cytokines in serum, and gene expression in bone were measured. Data were analyzed using 1-factor ANOVA. RESULTS: Compared with those fed the NF, mice fed the HFs had 19.6% higher fat mass (P < 0.01) and 13.5% higher concentration of serum tartrate-resistant acid phosphatase (TRAP) (P < 0.05), a bone resorption cytokine. Mice fed the HFs had 19.5% and 12.2% lower tibial and second lumbar vertebral bone mass, respectively (P < 0.01). Decreasing the dietary ratio of LA to ALA from 10 to 4 did not affect body mass, fat mass, serum TRAP and TNF-α, or any bone structural parameters. CONCLUSIONS: These data indicate that decreasing the dietary ratio of LA to ALA from 10 to 4 by simply reducing LA intake does not prevent adiposity or improve bone structure in obese mice.

Effects of parental dietary linoleic acid on growth performance, antioxidant capacity, and lipid metabolism in domestic pigeons (Columba livia).

The objective of this study was to evaluate the effects of dietary linoleic acid (LA) on growth performance, antioxidant capacity, and lipid metabolism in pigeon squabs by supplementing LA in their parental diets. A completely randomized design that consisted of a control group, 1% dietary LA addition group (LA1%), 2% dietary LA addition group (LA2%), and 4% dietary LA addition group (LA4%) was used. Six squabs from each treatment were randomly sampled at the day of hatch and days 7, 14, and 21 after hatch. The results showed that parental dietary LA had no significant influence (P > 0.05) on body weight (BW) gain or relative organ weights (% of BW) in squabs. The activities of superoxide dismutase, catalase, and glutathione peroxidase in the LA1% were significantly increased (P < 0.05) compared with those in the control group. The malondialdehyde content in the LA1% was significantly lower (P < 0.05) than that in the control group. The levels of serum triglyceride in the LA1% and LA2% were significantly decreased (P < 0.05) compared with those in the control group, whereas the serum high-density lipoprotein cholesterol level in the LA1% and LA2% and the free fatty acid level in the LA4% were significantly higher (P < 0.05) than those of the control group. The activities of lipoprotein lipase, hepatic lipase, and hormone-sensitive lipase in the LA1% were significantly higher (P < 0.05) than those in the control group. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in the LA1% and the hormone-sensitive lipase activity in the LA4% were significantly decreased (P < 0.05) compared with those in the control group. The mRNA expression of carnitine palmitoyltransferase 1, acyl-CoA 1, and peroxisome proliferator-activated receptor α was significantly upregulated (P < 0.05) in the LA1% compared with that in the control group. The Oil Red O staining area in the LA1% and LA2% was significantly reduced compared with that in the control group. The results indicated that although supplemental LA had negligible effects on growth and development in pigeon squabs, parental dietary LA at a concentration of 1% could have beneficial effects on maintaining squabs healthy as reflected by improved antioxidant capacity and lipid metabolism.

Oral Administration of Alpha Linoleic Acid Rescues Aß-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice.

In this work, we evaluated the effects of alpha linoleic acid (ALA), an omega-3 polyunsaturated fatty acid, on amyloid-beta-induced glial-cell-mediated neuroinflammation, amyloidogenesis, and cognitive dysfunction in mice. After an infusion of Aß1-42 (Aß1-42, 5 µL/5 min/mouse, intracerebroventricular injection (i.c.v), and respective treatments of ALA (60 mg/kg per oral for six weeks), neuroinflammation, apoptotic markers, and synaptic markers were evaluated by Western blot and immunofluorescence analyses. According to our findings, the infusion of Aß1-42 activated Toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the frontal cortices and hippocampi of the Aß1-42-injected mice to a greater extent than the Aß1-42 + ALA-cotreated mice. Similarly, there was an elevated expression of phospho-c-Jun-N-terminal kinase (p-JNK), phospho-nuclear factor-kB p65 (p-NF-kB p65 (Ser536)), and tissue necrosis factor (TNF) in the Aß1-42 infused mouse brains; interestingly, these markers were significantly reduced in the Aß + ALA-cotreated group. The elevated expression of pro-apoptotic markers was observed during apoptotic cell death in the Aß1-42-treated mouse brains, whereas these markers were markedly reduced in the Aß + ALA-cotreated group. Moreover, Aß1-42 infusion significantly increased amyloidogenesis, as assessed by the enhanced expression of the amyloid precursor proteins (APP) beta-amyloid cleaving enzyme-1 (BACE-1) and amyloid-beta (Aß1-42) in the mouse brains, whereas these proteins were markedly reduced in the Aß + ALA-cotreated group. We also checked the effects of ALA against Aß-triggered synaptic dysfunction and memory dysfunction, showing that ALA significantly improved memory and synaptic functions in Aß-treated mouse brains. These results indicated that ALA could be an applicable intervention in neuroinflammation, apoptotic cell loss, amyloidogenesis, and memory dysfunction via the inhibition of TLR4 and its downstream targets in Aß + ALA-cotreated mouse brains.