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

Jesuthasan, A., Zhyzhneuskaya, S., Peters, C., Barnes, A. C., Hollingsworth, K. G., Sattar, N. , Lean, M. E.J. , Taylor, R. and Al-Mrabeh, A. H. (2022) Sex differences in intraorgan fat levels and hepatic lipid metabolism: implications for cardiovascular health and remission of type 2 diabetes after dietary weight loss. Diabetologia, 65(1), pp. 226-233. (doi: 10.1007/s00125-021-05583-4) (PMID:34657182)

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Abstract

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.

Item Type:Articles
Additional Information:This study was funded by Diabetes UK (award number 13/0004691) and was supported by facilities of the National Institute for Health Research Newcastle Biomedical Research Centre.
Keywords:Remission of diabetes, intraorgan fat, hepatic VLDL1-TG, sex, lipid metabolism, abdominal fat, cardiovascular disease, weight loss, type 2 diabetes.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lean, Professor Michael and Sattar, Professor Naveed
Authors: Jesuthasan, A., Zhyzhneuskaya, S., Peters, C., Barnes, A. C., Hollingsworth, K. G., Sattar, N., Lean, M. E.J., Taylor, R., and Al-Mrabeh, A. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Diabetologia
Publisher:Springer
ISSN:0012-186X
ISSN (Online):1432-0428
Published Online:16 October 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Diabetologia 65(1): 226-233
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190677Reversal of T2DM to normal glucose tolerance using non-surgical weight management with low-energy-liquid-diet and long-term maintenance, within routine NHS care.Michael LeanDiabetes UK (DIABETUK)13/0004691Med - Human Nutrition