Abstract
Background Marine sourced N3-PUFA regulate lipid metabolism in adipose tissue and liver; however, less is known about plant sourced N3-PUFA. The goal of this study was to investigate plant and marine N3-PUFA regulation of fatty acid trafficking along the adipose tissue-liver axis according to nutritional state. Methods Mice were fed low-fat diets (7% w/w) containing either lard, flaxseed, or menhaden oils for 8 weeks, and were euthanized in either fed or fasted states. Substrate utilization and physical activity were assessed during the transition from a fed to fasted state. Plasma biomarkers (triglycerides (TAG), non-esterified fatty acids (NEFA)), as well as liver and epididymal adipose tissue (eWAT) lipogenic and lipolytic markers, were measured. Results Neither plant nor marine N3-PUFA influenced substrate utilization or activity during the transition from a fed to fasted state. In the fed state, marine N3-PUFA reduced plasma TAG levels compared to the other diets, with no further reduction seen in fasted mice. Hepatic lipogenic markers (Fasn, Acc, Scd1, and Elovl6) were reduced in the fed state with marine N3-PUFA, but not plant N3-PUFA. In the fasted state, mice fed either N3-PUFA accumulated less liver TAG, had lower plasma NEFA, and suppressed eWAT HSL activity compared to lard. Conclusion Marine N3-PUFA are more potent regulators of lipogenesis than plant N3-PUFA in the fed state, whereas both N3-PUFA influence eWAT lipolysis and plasma NEFA in the fasted state. This work provides novel insights regarding N3-PUFA regulation of fatty acid trafficking along the adipose tissue-liver axis according to nutritional state.
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Key Points
Dietary omega-3 polyunsaturated fatty acids (N3-PUFA) are one factor known to influence fatty acid metabolism in both adipose tissue and liver. N3-PUFA can decrease blood TAG levels, suppress DNL, regulate lipolysis, and promote fatty acid oxidation in rodents and human. Mechanistic studies directly comparing different N3-PUFA are lacking. Therefore, the present study had three objectives designed to investigate how diets supplemented with either plant or marine N3-PUFA influence fatty acid trafficking along the adipose tissue- liver axis in different nutritional states. The first objective was to determine if N3-PUFA influence substrate utilization during the transition from a fed to fasted state. The second objective was to assess if N3-PUFA regulate markers of lipogenesis and lipolysis in liver and epididymal white adipose tissue (eWAT) in the fed and fasted states. The third objective was to directly compare the effects of plant and marine N3-PUFA on these endpoints. It was hypothesized that marine N3-PUFA would regulate lipid metabolism along the adipose tissue-liver axis to a greater extent than plant N3-PUFA, independent of nutritional state. Short-term periods of feeding and fasting present a unique opportunity to investigate the role of dietary interventions in the context of alterations in metabolic demand. The present study has generated new insights regarding the distinct effects of low-fat diets rich in plant and marine N3-PUFA on lipid metabolism according to nutritional state. Continuous monitoring of O 2 consumption and CO 2 production during the transition from a fed to fasted state revealed that metabolic flexibility was not affected by either N3- PUFA in the context of a low-fat diet. In the fed state, the M-diet reduced plasma TAG compared to the L-diet. Further, the M-diet suppressed the expression of key hepatic lipogenic genes and corresponding proteins in the fed state, with less consistent effects seen in the fasted state. In contrast, the reduction in eWAT lipogenic genes and proteins with the M-diet were less pronounced, suggesting potential tissue-specific differences in N3-PUFA regulation of DNL. N3-PUFA diets blunted the increase in plasma NEFA in the fasted state, which was reflected by a lower accumulation of hepatic TAG in this same state. Collectively, this study showed that marine N3-PUFA are more potent regulators of fatty acid trafficking along the adipose tissue-liver axis than plant N3-PUFA. It was found that plant and marine N3-PUFA do not influence metabolic flexibility during the transition from fed to fasted states. Further, plant and marine N3-PUFA promote different outcomes related to fatty acid trafficking along the adipose tissue- liver axis that vary according to nutritional state. Interestingly, both types of N3-PUFA appear to regulate adipose tissue lipolysis similarly in the fasted state, while only marine N3-PUFA influence hepatic DNL and plasma TAG in the fed state. This study provides new insights as to the role of different N3- PUFA in modulating fatty acid trafficking along the adipose tissue- liver axis according to nutritional state.