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Sex differences in intraorgan fat levels and hepatic lipid metabolism: implications for cardiovascular health and remission of type 2 diabetes after dietary weight loss

Lookup NU author(s): Dr Sviatlana Zhyzhneuskaya, Dr Carl Peters, Alison Barnes, Dr Kieren Hollingsworth, Dr Naweed Sattar, Professor Roy Taylor, Dr Ahmad Al-Mrabeh



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2021, The Author(s).Aims/hypothesis: Type 2 diabetes confers a greater relative increase in CVD risk in women compared with men. We examined sex differences in intraorgan fat and hepatic VLDL1-triacylglycerol (VLDL1-TG) export before and after major dietary weight loss. Methods: A group with type 2 diabetes (n = 64, 30 male/34 female) and a group of healthy individuals (n = 25, 13 male/12 female) were studied. Intraorgan and visceral fat were quantified by magnetic resonance and VLDL1-TG export by intralipid infusion techniques. Results: Triacylglycerol content of the liver and pancreas was elevated in people with diabetes with no sex differences (liver 16.4% [9.3–25.0%] in women vs 11.9% [7.0–23.1%] in men, p = 0.57, and pancreas 8.3 ± 0.5% vs 8.5 ± 0.4%, p = 0.83, respectively). In the absence of diabetes, fat levels in both organs were lower in women than men (1.0% [0.9–1.7%] vs 4.5% [1.9–8.0%], p = 0.005, and 4.7 ± 0.4% vs 7.6 ± 0.5%, p< 0.0001, respectively). Women with diabetes had higher hepatic VLDL1-TG production rate and plasma VLDL1-TG than healthy women (559.3 ± 32.9 vs 403.2 ± 45.7 mg kg−1 day−1, p = 0.01, and 0.45 [0.26–0.77] vs 0.25 [0.13–0.33] mmol/l, p = 0.02), whereas there were no differences in men (548.8 ± 39.8 vs 506.7 ± 29.2 mg kg−1 day−1, p = 0.34, and 0.72 [0.53–1.15] vs 0.50 [0.32–0.68] mmol/l, p = 0.26). Weight loss decreased intraorgan fat and VLDL1-TG production rates regardless of sex, and these changes were accompanied by similar rates of diabetes remission (65.4% vs 71.0%) and CVD risk reduction (59.8% vs 41.5%) in women and men, respectively. Conclusions/interpretation: In type 2 diabetes, women have liver and pancreas fat levels as high as those of men, associated with raised hepatic VLDL1-TG production rates. Dynamics of triacylglycerol turnover differ between sexes in type 2 diabetes and following weight loss. These changes may contribute to the disproportionately raised cardiovascular risk of women with diabetes. Graphical abstract: [Figure not available: see fulltext.].

Publication metadata

Author(s): Jesuthasan A, Zhyzhneuskaya S, Peters C, Barnes AC, Hollingsworth KG, Sattar N, Lean MEJ, Taylor R, Al-Mrabeh AH

Publication type: Article

Publication status: Published

Journal: Diabetologia

Year: 2021

Volume: 65

Pages: 226-233

Online publication date: 16/10/2021

Acceptance date: 29/07/2021

Date deposited: 05/01/2023

ISSN (print): 0012-186X

ISSN (electronic): 1432-0428

Publisher: Springer Science and Business Media Deutschland GmbH


DOI: 10.1007/s00125-021-05583-4


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Funder referenceFunder name
13/0004691Diabetes UK