A peer-reviewed open access journal published by the National Institute of Environmental Health Sciences

Suppressing hyperactive endocannabinoid tone is a critical target for reducing obesity. The backbone of both endocannabinoids 2‐arachidonoylglycerol (2‐AG) and anandamide (AEA) is the ω‐6 fatty acid arachidonic acid (AA). Here we posited that excessive dietary intake of linoleic acid (LA), the precursor of AA, would induce endocannabinoid hyperactivity and promote obesity. LA was isolated as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% occurring in the United States during the 20th century. Mice were fed diets containing 1 en% LA, 8 en% LA, and 8 en% LA + 1 en% eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) in medium‐fat diets (35 en% fat) and high‐fat diets (60 en%) for 14 weeks from weaning. Increasing LA from 1 en% to 8 en% elevated AA‐phospholipids (PL) in liver and erythrocytes, tripled 2‐AG + 1‐AG and AEA associated with increased food intake, feed efficiency, and adiposity in mice. Reducing AA‐PL by adding 1 en% long‐chain ω‐3 fats to 8 en% LA diets resulted in metabolic patterns resembling 1 en% LA diets. Selectively reducing LA to 1 en% reversed the obesogenic properties of a 60 en% fat diet. These animal diets modeled 20th century increases of human LA consumption, changes that closely correlate with increasing prevalence rates of obesity. In summary, dietary LA increased tissue AA, and subsequently elevated 2‐AG + 1‐AG and AEA resulting in the development of diet‐induced obesity. The adipogenic effect of LA can be prevented by consuming sufficient EPA and DHA to reduce the AA‐PL pool and normalize endocannabinoid tone.

Depression is a common disorder affecting 10–15% women in the postpartum period. Postpartum depression can disrupt early mother-infant interaction, and constitutes a risk factor for early child development. Recently, attention has been drawn to the hypothesis that a low intake of seafood in pregnancy can be a risk factor for postpartum depression. Seafood is a unique dietary source of the marine omega-3 fatty acids and is a natural part of a healthy balanced diet that is especially important during pregnancy. In a community based prospective cohort in a municipality in Western Norway, we investigated both nutritional and psychological risk factors for postpartum depression. The source population was all women who were pregnant within the period November 2009 - June 2011. The fatty acid status in red blood cells was assessed in the 28^th gestation week and participants were screened for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS) three months after delivery. The aim of the present study was to investigate if a low omega-3 index in pregnancy is a possible risk factor for postpartum depression. In a simple regression model, the omega-3 index was associated with the EPDS score in a nonlinear inverse manner with an R square of 19. Thus, the low omega-3 index explained 19% of the variance in the EPDS score. The DPA content, DHA content, omega-3 index, omega-3/omega-6 ratio, total HUFA score, and the omega-3 HUFA score were all inversely correlated with the EPDS score. The EPDS scores of participants in the lowest omega-3 index quartile were significantly different to the three other omega-3 index quartiles. In this study population, a low omega-3 index in late pregnancy was associated with higher depression score three months postpartum.

Dietary intake of linoleic acid (LNA, 18:2n‐6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n‐6) is the precursor for 2‐AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA–PL), elevated 2‐AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.