Commentary

Linoleic acid recommendations—A house of cards

After surgical or natural menopause, women face a high risk of nonalcoholic fatty liver disease (NAFLD), which can be diminished by hormone replacement therapy (HRT). The gut microbiota is subject to modulation by various physiological changes and the progression of diseases. This microbial ecosystem coexists symbiotically with the host, playing pivotal roles in immune maturation, microbial defense mechanisms, and metabolic functions essential for nutritional and hormone homeostasis. E₂ supplementation effectively prevented the development of NAFLD after bilateral oophorectomy (OVX) in female rats. The changes in the gut microbiota such as abnormal biosynthetic metabolism of fatty acids caused by OVX were partially restored by E₂ supplementation. The combination of liver transcriptomics and metabolomics analysis revealed that linoleic acid (LA) metabolism, a pivotal pathway in fatty acids metabolism was mainly manipulated during the induction and treatment of NAFLD. Further correlation analysis indicated that the gut microbes were associated with abnormal serum indicators and different LA metabolites. These metabolites are also closely related to serum indicators of NAFLD. An in vitro study verified that LA is an inducer of hepatic steatosis. The changes in transcription in the LA metabolism pathway could be normalized by E₂ treatment. The metabolic perturbations of LA may directly and secondhand impact the development of NAFLD in postmenopausal individuals. This research focused on the sex-specific pathophysiology and treatment of NAFLD, providing more evidence for HRT and calling for the multitiered management of NAFLD.

COVID-19 symptoms vary from silence to rapid death, the latter mediated by both a cytokine storm and a thrombotic storm. SARS-CoV (2003) induces Cox-2, catalyzing the synthesis, from highly unsaturated fatty acids (HUFA), of eicosanoids and docosanoids that mediate both inflammation and thrombosis. HUFA balance between arachidonic acid (AA) and other HUFA is a likely determinant of net signaling to induce a healthy or runaway physiological response. AA levels are determined by a non-protein coding regulatory polymorphisms that mostly affect the expression of FADS1, located in the FADS gene cluster on chromosome 11. Major and minor haplotypes in Europeans, and a specific functional insertion-deletion (Indel), rs66698963, consistently show major differences in circulating AA (>50%) and in the balance between AA and other HUFA (47–84%) in free living humans; the indel is evolutionarily selective, probably based on diet. The pattern of fatty acid responses is fully consistent with specific genetic modulation of desaturation at the FADS1-mediated 20:3→20:4 step. Well established principles of net tissue HUFA levels indicate that the high linoleic acid and low alpha-linoleic acid in populations drive the net balance of HUFA for any individual. We predict that fast desaturators (insertion allele at rs66698963; major haplotype in Europeans) are predisposed to higher risk and pathological responses to SARS-CoV-2 could be reduced with high dose omega-3 HUFA.

This study aimed to estimate the influences of flax oil and a mixture of ethyl esters of fatty acids from flax oil added to a milk replacer (MR) formulation on the biochemical, immunological, and antioxidant status of blood, production parameters, and health of calves. Twenty-seven Holstein-Frisian calves were assigned to 3 groups: the control group without fat added to the diet (CON, n = 9), a group receiving ethyl esters of flax oil (10 g/d) with lyophilized apples (25 g; MRE), or a group receiving flax oil (10 g/d) with lyophilized apples (25 g; MRL). The study was conducted from d 14 to d 42 of life. Intake of MR and feed were recorded daily, and fecal scores, rectal temperature, and body weight were recorded weekly. Laboratory blood tests were conducted every 7 d from d 14 to 42. Supplementation with the formulation containing ethyl esters of flax oil (MRE) positively affected health, average daily weight gain, growth rate, and feed efficiency. Intake of the starter feed was lower in the calves receiving the formulation with flax oil (MRL). The MRE formulations lowered the concentrations of triglycerides, total cholesterol, and LDL fraction in blood serum and decreased the total antioxidant capacity (TAS) and levels of glutathione peroxidase (GPx). The MRL formulation increased TAS and GPx levels in blood serum. The MRE treatment limited the circulating levels of tumor necrosis factor. The MRE and MRL preparations lowered the concentration of SFA (C16:0, C18:0, C18:1) in blood serum, and MRE significantly increased levels of α-linolenic acid. The MRE and MRL preparations beneficially affected production and physiological parameters. Our data support the idea that supplementation with n-3 fatty acids improves calf growth and metabolic and oxidative functions in young calves.

Why would anyone be interested in lipids and fatty acids for more than 50 years? It is because this field is fascinating, because there is such a great variety of research and application in biology, medicine, agriculture, and nutrition, and many of the discoveries are of fundamental importance to everyday lives. It only takes a few minutes of searching PubMed (https://www.ncbi.nlm.nih.gov/pubmed) to realize that nutrition is being overrun by large-scale research studies, many of which involves the microbiome, with huge teams, including experts in molecular biology, metabolomics, bioinformatics, medicine, immunology, and the microbiome itself. However, it is encouraging that lipid scientists and multidisciplinary collaborators in fields such as arthritis, chronic headache pain relief, maternal and infant nutrition, psychiatry and basic brain research, are conducting multidisciplinary studies. The future is bright if such multidisciplinary collaborations continue.

The modern Western diet has been consumed in developed English speaking countries for the last 50 years, and is now gradually being adopted in Eastern and developing countries. These nutrition transitions are typified by an increased intake of high linoleic acid (LA) plant oils, due to their abundance and low price, resulting in an increase in the PUFA n-6:n-3 ratio. This increase in LA above what is estimated to be required is hypothesised to be implicated in the increased rates of obesity and other associated non-communicable diseases which occur following a transition to a modern Westernised diet. LA can be converted to the metabolically active arachidonic acid, which has roles in inducing inflammation and adipogenesis, and endocannabinoid system regulation. This review aims to address the possible implications of excessive LA and its metabolites in the pathogenesis of obesity.