ORCID Profile
0000-0002-2648-6526
Current Organisation
University of Oxford
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Publisher: Wiley
Date: 27-07-2016
DOI: 10.1111/ECI.12657
Abstract: Experimental data suggest that apolipoprotein (apo) C-II and C-III regulate triglyceride-rich lipoprotein (TRL) metabolism, but there are limited studies in humans. We investigated the metabolic associations of TRLs with apoC-II and apoC-III concentrations and kinetics in women. The kinetics of plasma apoC-II, apoC-III and very low-density lipoprotein (VLDL) apoB-100 and triglycerides were measured in the postabsorptive state using stable isotopic techniques and compartmental modelling in 60 women with wide-ranging body mass index (19·5-32·9 kg/m(2) ). Plasma apoC-II and apoC-III concentrations were positively associated with the concentrations of plasma triglycerides, VLDL1 - and VLDL2 -apoB-100 and triglyceride (all P < 0·05). ApoC-II production rate (PR) was positively associated with VLDL1 -apoB-100 concentration, VLDL1 triglyceride concentration and VLDL1 triglyceride PR, while apoC-II fractional catabolic rate (FCR) was positively associated with VLDL1 triglyceride FCR (all P < 0·05). No significant associations were observed between apoC-II and VLDL2 apoB-100 or triglyceride kinetics. ApoC-III PR, but not FCR, was positively associated with VLDL1 triglyceride, and VLDL2 -apoB-100 and triglyceride concentrations (all P < 0·05). No significant associations were observed between apoC-III and VLDL-apoB-100 and triglyceride kinetics. In multivariable analysis, including homoeostasis model assessment score, menopausal status and obesity, apoC-II concentration was significantly associated with plasma triglyceride, VLDL1 -apoB-100 and VLDL1 triglyceride concentrations and PR. Using the same multivariable analysis, apoC-III was significantly associated with plasma triglyceride and VLDL1 - and VLDL2 -apoB-100 and triglyceride concentrations and FCR. In women, plasma apoC-II and apoC-III concentrations are regulated by their respective PR and are significant, independent determinants of the kinetics and plasma concentrations of TRLs.
Publisher: eLife Sciences Publications, Ltd
Date: 05-08-2021
DOI: 10.7554/ELIFE.63324
Abstract: The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global Nr1d1 deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion ( Nr1d1 Flox2-6 :Adipoq Cre ), and transcriptional profiling demonstrates that, under basal conditions, direct targets of NR1D1 regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, Nr1d1 Flox2-6 :Adipoq Cre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT NR1D1 cistrome with differential gene expression reveals broad control of metabolic processes by NR1D1 which is unmasked in the obese state. Adipocyte NR1D1 does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, NR1D1 action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.
Publisher: Proceedings of the National Academy of Sciences
Date: 28-09-2020
Abstract: The circadian clock protein REVERBα is proposed to be a key regulator of liver metabolism. We now show that REVERBα action is critically dependent on metabolic state. Using transgenic mouse models, we show that the true role of REVERBα is to buffer against aberrant responses to metabolic perturbation, rather than confer rhythmic regulation to programs of lipid synthesis and storage, as has been thought previously. Thus, in the case of liver metabolism, the clock does not so much drive rhythmic processes, as provide protection against mistimed feeding cues. Understanding how the clock is coupled to metabolism is critical for understanding metabolic disease and the impacts of circadian disruptors such as shift work and 24-h lifestyles.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2012
DOI: 10.1161/HYPERTENSIONAHA.112.197897
Abstract: Obesity and excessive lipolysis are implicated in preecl sia (PE). Intrauterine growth restriction is associated with low maternal body mass index and decreased lipolysis. Our aim was to assess how maternal and offspring fatty acid metabolism is altered in mothers in the third trimester of pregnancy with PE (n=62) or intrauterine growth restriction (n=23) compared with healthy pregnancies (n=164). Markers of lipid metabolism and erythrocyte fatty acid concentrations were measured. Maternal adipose tissue fatty acid composition and mRNA expression of adipose tissue fatty acid–metabolizing enzymes and placental fatty acid transporters were compared. Mothers with PE had higher plasma triglyceride (21%, P .001) and nonesterified fatty acid (50%, P .001) concentrations than controls. Concentrations of major n−6 and n−3 long-chain polyunsaturated fatty acids in erythrocytes were 23% to 60% lower (all P .005) in PE and intrauterine growth restriction mothers and offspring compared with controls. Subcutaneous adipose tissue Δ−5 and Δ−6 desaturase and very long-chain fatty acid elongase mRNA expression was lower in PE than controls (respectively, mean [SD] control 3.38 [2.96] versus PE 1.83 [1.91], P =0.030 3.33 [2.25] versus 1.03 [0.96], P .001 0.40 [0.81] versus 0.00 [0.00], P =0.038 expression relative to control gene [square root]). Low maternal and fetal long-chain polyunsaturated fatty acid concentrations in PE may be the result of decreased maternal synthesis.
Publisher: Elsevier BV
Date: 2014
Abstract: Erythrocytes, compared with plasma, are considered more robust markers of n-3 (ω-3) polyunsaturated fatty acid (PUFA) intake, because dietary-induced change in fatty acid (FA) composition takes longer to complete. The extent to which this applies to intakes of saturated fatty acid (SFA) or n-6 PUFA is unclear. We compared the pattern of change over time in the fatty acid composition of plasma, erythrocyte, buccal cell, and adipose tissue lipids when changing between diets high in SFA or n-6 PUFA. Twenty-four (n = 7 male) healthy participants were instructed to consume either an SFA-rich (18% energy) or n-6 PUFA-rich (10% energy) diet for 8 wk before crossing over, without washout, to the alternate diet. The FA composition of plasma triacylglycerol (TG), nonesterified FAs, cholesterol ester, total phospholipids, erythrocyte total phospholipids, erythrocyte phosphatidylcholine, and buccal cell total phospholipids was measured every 2 wk and adipose tissue TG every 4 wk during the 16-wk intervention. Linoleic acid composition of plasma, erythrocyte, and buccal cell lipids increased (P < 0.01) during the first 2 wk of the n-6 PUFA diet and remained unchanged during the remaining 6 wk. During the 8-wk SFA diet, the same pattern of change over time occurred for the pentadecanoic acid composition of plasma and erythrocyte lipids however, the pentadecanoic acid composition of buccal cell lipids did not differ between the diet periods. There were no differences in linoleic or pentadecanoic acid composition of adipose tissue TG. These results suggest plasma and erythrocyte FAs reflect intakes of SFA and n-6 PUFA over a similar period of time.
Publisher: MDPI AG
Date: 20-01-2011
DOI: 10.3390/NU3010152
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-10-2015
Abstract: Android fat distribution (abdominal obesity) is associated with insulin resistance, hepatic steatosis, and greater secretion of large very low‐density lipoprotein ( VLDL ) particles in men. Since abdominal obesity is becoming increasingly prevalent in women, we aimed to investigate the relationship between android fat and hepatic lipid metabolism in pre‐ and postmenopausal women. We used a combination of stable isotope tracer techniques to investigate intrahepatic fatty acid synthesis and partitioning in 29 lean and 29 abdominally obese women (android fat/total fat 0.065 [0.02 to 0.08] and 0.095 [0.08 to 0.11], respectively). Thirty women were premenopausal aged 35 to 45 and they were matched for abdominal obesity with 28 postmenopausal women aged 55 to 65. As anticipated, abdominal obese women were more insulin resistant with enhanced hepatic secretion of large (404±30 versus 268±26 mg/kg lean mass, P .001) but not small VLDL (160±11 versus 142±13). However, postmenopausal status had a pronounced effect on the characteristics of small VLDL particles, which were considerably triglyceride‐enriched (production ratio of VLDL 2 ‐ triglyceride:apolipoprotein B 30±5.3 versus 19±1.6, P .05). In contrast to postmenopausal women, there was a tight control of hepatic fatty acid metabolism and triglyceride production in premenopausal women, whereby oxidation ( r s =−0.49, P =0.006), de novo lipogenesis ( r s =0.55, P =0.003), and desaturation ( r s =0.48, P =0.012) were closely correlated with abdominal obesity‐driven large VLDL ‐triglyceride secretion rate. In women, abdominal obesity is a major driver of hepatic large VLDL particle secretion, whereas postmenopausal status was characterized by increased small VLDL particle size. These data provide a mechanistic basis for the hyperlipidemia observed in postmenopausal obesity.
Publisher: Cold Spring Harbor Laboratory
Date: 25-09-2020
DOI: 10.1101/2020.09.23.308155
Abstract: The circadian clock component REVERBα is considered a dominant regulator of lipid metabolism, with global Reverbα deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion ( Reverbα Flox2-6 Adipo Cre ), and transcriptional profiling demonstrates that, under basal conditions, direct targets of REVERBα regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, Reverbα Flox2-6 Adipo Cre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT REVERBα cistrome with differential gene expression reveals broad control of metabolic processes by REVERBα which is unmasked in the obese state. Adipocyte REVERBα does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, REVERBα action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Leanne Hodson.