Objective: The objective was to determine the safety and efficacy of a fish oil-based intravenous lipid emulsion (ILE) in the treatment of parenteral nutrition-associated liver disease (PNALD). Summary and Background Data: PNALD can be a lethal complication in children with short bowel syndrome (SBS). ILE based on soybean oil administered with parenteral nutrition (PN) may contribute to its etiology. Methods: We performed an open-labeled trial of a fish oil-based ILE in 42 infants with SBS who developed cholestasis (serum direct bilirubin >2 mg/dL) while receiving soybean oil-based ILE. Safety and efficacy outcomes were compared with those from a contemporary cohort of 49 infants with SBS and cholestasis whose PN course included soybean ILE only. The primary efficacy end-point was time to reversal of cholestasis (direct bilirubin ≤2 mg/dL). Results: Three deaths and 1 liver transplantation occurred in the fish oil cohort, compared with 12 deaths and 6 transplants in the soybean oil cohort (P = 0.005). Among survivors not transplanted during PN, cholestasis reversed while receiving PN in 19 of 38 patients in the fish oil cohort versus 2 of 36 patients in the soybean oil cohort. Based on Cox models, subjects receiving fish oil-based ILE experienced reversal of cholestasis 6 times faster (95% CI: 2.0–37.3) than those receiving soybean oil-based ILE. The provision of fish oil-based ILE was not associated with hypertriglyceridemia, coagulopathy, or essential fatty acid deficiency. Moreover, hypertriglyceridemic events and abnormal international normalized ratio levels were more common among controls. Conclusions: Fish oil-based ILE is safe, may be effective in treating PNALD, and may reduce mortality and organ transplantation rates in children with SBS.

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

Summary: Women approaching advanced maternal age have extremely poor outcomes with both natural and assisted fertility. Moreover, the incidence of chromosomal abnormalities and birth defects increases with age. As of yet, there is no effective and practical strategy for delaying ovarian aging or improving oocyte quality. We demonstrate that the lifelong consumption of a diet rich in omega‐3 fatty acids prolongs murine reproductive function into advanced maternal age, while a diet rich in omega‐6 fatty acids is associated with very poor reproductive success at advanced maternal age. Furthermore, even short‐term dietary treatment with a diet rich in omega‐3 fatty acids initiated at the time of the normal age‐related rapid decline in murine reproductive function is associated with improved oocyte quality, while short‐term dietary treatment with omega‐6 fatty acids results in very poor oocyte quality. Thus, omega‐3 fatty acids may provide an effective and practical avenue for delaying ovarian aging and improving oocyte quality at advanced maternal age.