Endocrine Abstracts

Background: Intrahepatic triglyceride (IHTG) accumulation, a cardiometabolic disease risk factor, is greater in individuals consuming saturated-fat (SFA) compared to polyunsaturated-fat (PUFA) enriched diets. We have demonstrated that compared to SFA, PUFA are preferentially partitioned into oxidation pathways, which may, in part, explain the divergence in IHTG accumulation. However, it remains unclear if this preferential handling is maintained when hepatocellular metabolism is shifted toward fatty acid (FA) esterification and away from oxidation, such as when hepatic de novo lipogenesis (DNL) is upregulated.

Aim: To investigate whether dietary-induced upregulation of hepatic DNL influences the partitioning of dietary FAs.

Methods: 20 healthy volunteers (11 females) underwent a fasting baseline visit followed by two postprandial study days (PSD), 2-weeks apart. Prior to each PSD, participants consumed an isocaloric high-sugar diet (to promote hepatic DNL) for 3-days. On the PSD, participants consumed an identical standardised test meal that contained a ¹³C-labelled FA (SFA ([U¹³C]palmitate) or PUFA ([U¹³C]linoleate)), in random order, to trace the fate of dietary FA. Blood and breath samples were collected over the 6h postprandial period and ¹³C enrichment in breath CO₂ and plasma lipid fractions were measured using gas chromatography/mass-spectrometry.

Results: Compared to the baseline visit, fasting plasma triglyceride concentrations and hepatic DNL were significantly (P<0.05) increased after consumpting the high-sugar diet. Appearance of ¹³C in expired CO₂ and tracer recovery were significantly (P<0.05) higher after consumption of the meal containing [U¹³C]linoleate compared to [U¹³C]palmitate (5.1±0.5% vs. 3.7±0.4%), respectively. Incorporation of ¹³C into the plasma triglyceride and non-esterified FA pool was significantly (P<0.001) greater for [U¹³C]palmitate compared to [U¹³C]linoleate.

Conclusion: Our findings demonstrate that the increased partitioning of SFA into esterification pathways, compared to PUFA, is maintained during dietary-induced DNL upregulation. This may reveal important mechanistic insights regarding SFA in cardiometabolic disease risk.