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Fig 1.

Simplified overview of the molecular alterations and corresponding conditions related to sphingolipid accumulation.

Abbreviations: FFA = free fatty acids, acyl-CoA = acyl-coenzyme A, PP2A = protein phosphatase 2 A, PKCζ = protein kinase C zeta, Akt = serine–threonine kinase Akt, HSL = hormone-sensitive lipase, CD36 = cluster of differentiation 36, also known as a fatty acid translocase, SREBP-1 = sterol regulatory element-binding transcription factor 1, TAG = triacylglycerides, MSS1 = mitochondrial fission factor 1, BAX = bcl-2-like protein 4, SMAD3 = Mothers against decapentaplegic homolog 3, NAFLD = non-alcoholic fatty liver disease, T2DM = type 2 diabetes mellitus, NASH = non-alcoholic steatohepatitis, CAD = coronary artery disease. Blue boxes highlight pathophysiological changes and related clinical conditions. This figure is based on [12, 17].

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Table 1.

Items from the World Health Organization trial registration data set.

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Table 2.

Inclusion and exclusion criteria.

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Fig 2.

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) schedule of enrolment, interventions, and assessments.

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Fig 3.

Schedule and sequence of study procedures as planned for study visits.

Abbreviations: ECG = electrocardiogram, CPET = cardio-pulmonary exercise testing, HIIT = high intensity interval training.

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Fig 4.

Study design.

Abbreviations: HIIT = high intensity interval training, Cer = Ceramide, VO2peak = peak oxygen uptake.

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Fig 5.

Sample size calculation.

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Fig 6.

Directed acyclic graph representing the effect of HIIT on sphingolipid levels and other influencing variables.

Abbreviations: HIIT = high-intensity interval training, CRF = cardiorespiratory fitness, PA = physical activity, SL = sphingolipid levels.

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