Previously, results from studies investigating if brain palmitic acid (16:0; PAM) was maintained by either dietary uptake or de novo lipogenesis (DNL) varied. Here, we utilize naturally occurring carbon isotope ratios (13C/12C; δ13C) to uncover the origin of brain PAM. Additionally, we explored brain and liver fatty acid concentration, brain metabolomics, and behavior. BALB/c dams were equilibrated onto either a low PAM diet (LP; <2%) or high PAM diet (HP; >95%) prior to producing one generation of offspring. Offspring stayed on the respective diet of the dam until 15‐weeks of age, at which time the Open Field test was conducted, prior to euthanasia and tissue lipid extraction. Although liver PAM was lower in mice fed the LP diet, as well as female mice, brain PAM was not affected by diet or sex. Across mice of either sex on both diets, brain 13C‐PAM revealed compared to dietary uptake, DNL from dietary sugars contributed 68.8%–79.5% and 46.6%–58.0% to the total brain PAM pool by both peripheral and local brain DNL, and local brain DNL alone, respectively. DNL was augmented in mice fed the LP diet, and the ability to up‐regulate DNL in the liver or the brain depended on sex. Anxiety‐like behaviors were decreased in mice fed the LP diet and were correlated with markers of LP diet consumption including increased liver 13C‐PAM, warranting further investigation. Altogether, our results indicate that DNL from dietary sugars is a compensatory mechanism to maintain brain PAM in response to the LP diet.

Background Palmitic acid (PA; 16:0) is added to infant formula in the form of palm oil/palm olein (PO/POL) and stereospecific numbered–2 palmitate (SN2). Several studies have examined the effects of PO/POL and or SN2 in formulas on health outcomes, mainly growth, digestion, and absorption of nutrients. However, the roles of PA, PO/POL, and SN2 on neurodevelopment remains unknown. Objectives The objective of this scoping review was to map out studies in infants fed formula with PO/POL or SN2 to identify current knowledge on the role of PA in infant nutrition, specifically neurodevelopment. Methods Data sources, including Medline, Embase, CAB Abstracts, and the Cochrane Database, were searched. Eligible articles were randomized controlled trials (RCTs) and observational studies examining outcomes in term singleton infants fed formula containing PO/POL or SN2. Studies examining preterm infants or infants with infections, mixed-feeding interventions, or outcomes not concerned with PO/POL or SN2 were excluded. Screening and data extraction were performed by 2 independent reviewers, and results were charted into 10 outcome categories. Results We identified 28 RCTs and 2 observational studies. Only 1 RCT examined a neurodevelopmental outcome, reporting infants fed SN2 formula had higher fine motor skill scores compared to those fed a vegetable oil formula with a lower amount of SN2; however, only after adjustment for maternal education and at an earlier, but not a later time point. Anthropometric measures do not appear to be influenced by PO/POL or SN2 within formulas. Alternatively, it was reported that infants fed PO/POL within formulas had a decreased absorption of calcium, total fat, and PA compared to those fed vegetable oil formulas. However, studies were heterogenous, making it difficult to isolate the effects of PO/POL or SN2 in formulas. Conclusions Our review reiterates the need for future studies to address the effects of PO/POL and SN2 on neurodevelopment in infants. This study is registered at Open Science Framework as osf.io/697he.

Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (n = 21) and non‐cannabis users (n = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon‐specific isotope analysis, which allows for the determination of fatty acid 13C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched 13C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2‐arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti‐inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.

The synthesis rates of n‐3 and n‐6 polyunsaturated fatty acids (PUFAs) in rodents and humans are not agreed upon and depend on substrate availability independently of the capacity for synthesis. Therefore, we aimed to assess the activities of the enzymes for n‐3 and n‐6 PUFA synthesis pathways in liver, brain, testicle, kidney, heart, and lung, in relation to their protein concentration levels. Eight‐week‐old Balb/c mice (n = 8) were fed a standard chow diet (6.2% fat, 18.6% protein, and 44.2% carbohydrates) until 14 weeks of age, anesthetized with isoflurane and tissue samples were collected (previously perfused) and stored at −80°C. The protein concentration of the enzymes (Δ‐6D, Δ‐5D, Elovl2, and Elovl5) were assessed by ELISA kits; their activities were assayed using specific PUFA precursors and measuring the respective PUFA products as fatty acid methyl esters by gas chromatographic analysis. The liver had the highest capacity for PUFA biosynthesis, with limited activity in the brain, testicles, and kidney, while we failed to detect activity in the heart and lung. The protein concentration and activity of the enzymes were significantly correlated. Furthermore, Δ‐6D, Δ‐5D, and Elovl2 have a higher affinity for n‐3 PUFA precursors compared to n‐6 PUFA. The capacity for PUFA synthesis in mice mainly resides in the liver, with enzymes having preference for n‐3 PUFAs.

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