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Endocrine Abstracts (2022) 86 OC5.5 | DOI: 10.1530/endoabs.86.OC5.5

SFEBES2022 Oral Communications Metabolism, Obesity and Diabetes (6 abstracts)

Upregulation of hepatic de novo lipogenesis dissociates from changes in liver fat content and insulin sensitivity in healthy humans

David Dearlove 1 , Siôn Parry 1 , Elspeth Johnson 1 , Thomas Cornfield 1 , Ferenc Mozes 2 , Pam Dyson 1 & Leanne Hodson 1,3


1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom; 2Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, United Kingdom; 3Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom


Introduction: Increased hepatic de novo lipogenesis (DNL) is often associated with greater intrahepatic triglyceride (IHTG) content and/or decreased insulin sensitivity; however, the contribution of DNL to each has not been fully elucidated. Therefore, the present work determined if increased DNL, achieved via adoption of an isocaloric high-sugar diet, resulted in concomitant increases in IHTG content and/or decreases in insulin sensitivity.

Methods: Sixteen healthy participants (6 females; (mean ± SD) aged 49 ± 4 years; BMI 27.7 ± 3.8 kg/m2; HOMA-IR 1.56 ± 1.44) adopted a high-sugar diet for up to 21 days (range 13-21 days). Fasting and postprandial metabolism were measured before and after the dietary intervention. Stable-isotope tracer methodology was utilised to assess fasting and postprandial hepatic DNL. Liver fat was measured before and after the dietary intervention by 1H-MRS using a 3 Tesla MRI scanner.

Results: Despite increasing the proportion of energy from sugar (113 ± 49 Kcal/day to 192 ± 55 Kcal/day; P=0.002), participants’ body weight was stable during the dietary intervention. Compared to baseline, consumption of the high-sugar diet significantly increased postprandial DNL by ~54.4% (P<0.001). IHTG was modestly increased by ~0.6% (P=0.006) and insulin sensitivity (HOMA-IR) was unchanged (P>0.05). There was neither an association between changes in DNL and IHTG (r=-0.2, P>0.05) nor DNL and HOMA-IR (r=0.2, P>0.05). Plasma triglyceride concentration was increased by 20% post-diet (P<0.001), and this change tended to be positively associated with the change in DNL (r=0.5, P=0.06).

Conclusion: Hepatic DNL may be dissociated from changes in liver fat content and insulin sensitivity in healthy individuals adopting a high-sugar diet. These observations suggest that DNL may not substantially contribute to IHTG accumulation when individuals can up-regulate hepatic triglyceride export, as evidenced by the increase in plasma TG concentrations.

Volume 86

Society for Endocrinology BES 2022

Harrogate, United Kingdom
14 Nov 2022 - 16 Nov 2022

Society for Endocrinology 

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