7 research outputs found

    The role of hepatic lipid composition in obesity-related metabolic disease

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    Obesity is a primary antecedent to non-alcoholic fatty liver disease whose cardinal feature is excessive hepatic lipid accumulation. Although total hepatic lipid content closely associates with hepatic and systemic metabolic dysfunction, accumulating evidence suggests that the composition of hepatic lipids may be more discriminatory. This review summarises cross-sectional human studies using liver biopsy/lipidomics and proton magnetic resonance spectroscopy to characterise hepatic lipid composition in people with obesity and related metabolic disease. A comprehensive literature search identified 26 relevant studies published up to 31st March 2021 which were included in the review. The available evidence provides a consistent picture showing that people with hepatic steatosis possess elevated saturated and/or monounsaturated hepatic lipids and a reduced proportion of polyunsaturated hepatic lipids. This altered hepatic lipid profile associates more directly with metabolic derangements, such as insulin resistance, and may be exacerbated in non-alcoholic steatohepatitis. Further evidence from lipidomic studies suggests that these deleterious changes may be related to defects in lipid desaturation and elongation, and an augmentation of the de novo lipogenic pathway. These observations are consistent with mechanistic studies implicating saturated fatty acids and associated bioactive lipid intermediates (ceramides, lysophosphatidylcholines and diacylglycerol) in the development of hepatic lipotoxicity and wider metabolic dysfunction, whilst monounsaturated fatty acids and polyunsaturated fatty acids may exhibit a protective role. Future studies are needed to prospectively determine the relevance of hepatic lipid composition for hepatic and non-hepatic morbidity and mortality; and to further evaluate the impact of therapeutic interventions such as pharmacotherapy and lifestyle interventions

    Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with MASLD but is not altered by six weeks of exercise training

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    Aims To examine the impact of impaired glycaemic regulation and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD).  Materials and methods In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF]≥5.56%) were recruited to one-of-two groups: 1) normal glycaemic regulation (NGR; HbA1c Results In Part A, hepatic SI was higher and hepatic UI was lower in the IGR vs. NGR group (P=0.038), and this hepatic lipid profile was associated with higher HbA1c, FPG, HOMA-IR and plasma CK18 M65 (rs≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX vs. CON (P≥0.257), while FPG was reduced and V̇O2 peak was increased (P≤0.030). ΔV̇O2 peak was inversely associated with Δhepatic SI (r=-0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r≥0.433).  Conclusions IGR in MASLD is characterised by greater hepatic lipid saturation, however, this composition is not altered by six-weeks of moderate-intensity exercise training. ClinicalTrials.gov: NCT04004273</div
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