The Contribution of Splanchnic Fat to VLDL Triglyceride Is Greater in Insulin-Resistant Than Insulin-Sensitive Men and Women

Hodson, Leanne; Bickerton, Alex; McQuaid, Siobhán; Roberts, Rachel; Karpe, Fredrik; Frayn, Keith N.; Fielding, Barbara A.

doi:10.2337/db07-0654

Cited by 93 publications

(123 citation statements)

References 46 publications

(56 reference statements)

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“…The liver takes up gives 4% of this [23]. Bickerton [8] shows adipose tissue uptake 3 times more than skeletal muscle, therefore adipose uptake given by 72% of 0.1386.…”

Section: Description Variable Steady Value Referencementioning

confidence: 99%

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Mathematical modelling of hepatic lipid metabolism

Pratt

Wattis

Salter

2015

Mathematical Biosciences

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The aim of this paper is to develop a mathematical model capable of simulating the metabolic response to a variety of mixed meals in fed and fasted conditions with particular emphasis placed on the hepatic triglyceride element of the model. Model validation is carried out using experimental data for the ingestion of three mixed composition meals over a 24-hour period. Comparison with experimental data suggests the model predicts key plasma lipids accurately given a prescribed insulin profile. One counter-intuitive observation to arise from simulations is that liver triglyceride initially decreases when a high fat meal is ingested, a phenomenon potentially explained by the carbohydrate portion of the meal raising plasma insulin.

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“…The liver takes up gives 4% of this [23]. Bickerton [8] shows adipose tissue uptake 3 times more than skeletal muscle, therefore adipose uptake given by 72% of 0.1386.…”

Section: Description Variable Steady Value Referencementioning

confidence: 99%

“…Hodson et al [23] estimate 4% of TAG is taken up from the remnant particles by the liver. Bickerton [8] estimates adipose tissue takes up 3 times more TAG than skeletal muscle.…”

Section: Description Variable Steady Value Referencementioning

confidence: 99%

Mathematical modelling of hepatic lipid metabolism

Pratt

Wattis

Salter

2015

Mathematical Biosciences

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“…One study found that VLDL‐TG secretion rate was significantly higher in pre‐menopausal women than men,31 whereas another found that VLDL 2 ‐TG but not VLDL 1 ‐TG secretion rate was higher in post‐menopausal women than men 24. We have previously reported no difference in the postprandial contribution of dietary and nonsystemic FA to VLDL‐TG between insulin‐sensitive men and women 13. However, lipoprotein metabolism is dependent on a many factors, and accumulation of excess body fat seems to affect lipid kinetics differently in men and women as recently discussed 50.…”

Section: Discussionmentioning

confidence: 85%

“…FA methyl esters prepared from VLDL 1 and VLDL 2 ‐TG FAs20 were analyzed by GC13 to quantify 16:0 and 16:1n‐7, and by GC‐Isotope Ratio Mass Spectrometer to measure isotopic enrichment 26…”

Section: Methodsmentioning

confidence: 99%

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Menopausal Status and Abdominal Obesity Are Significant Determinants of Hepatic Lipid Metabolism in Women

Hodson

Banerjee

Rial

et al. 2015

JAHA

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BackgroundAndroid 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.Methods and ResultsWe 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<0.001) 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<0.05). 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.ConclusionsIn 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.

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Omega‐3 polyunsaturated fatty acids and proanthocyanidins improve postprandial metabolic flexibility in rat

et al. 2013

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Postprandial lipemia influences the development of atherosclerosis, which itself constitutes a risk factor for the development of cardiovascular diseases. The introduction of bioactive compounds may prevent these deleterious effects. Proanthocyanidins are potent antioxidants that have hypolipidemic properties, while omega-3 polyunsaturated fatty acids (ω3 PUFAs) stimulate fatty acid oxidation and gene expression programs, controlling mitochondrial functions. In this study, we investigated the effects of acute treatment of ω3 PUFAs and proanthocyanidins on the metabolic flexibility and lipid handling profiles in the skeletal muscle and adipose tissue of rats that were raised on diets, high in saturated fatty acids. For this, oil rich in docosahexaenoic (DHA-OR), grape seed proanthocyanidins extract (GSPE), or both substances (GSPE + DHA-OR) were administered with an overload of lard oil to healthy Wistar rats. Our results indicate that the addition of DHA-OR to lard oil increases insulin sensitivity and redirects fatty acids toward skeletal muscle, thereby activating fatty acid oxidation. We also observed an improvement in adipose mitochondrial functionality and uncoupling. In contrast, GSPE lowers lipidemia, prevents muscle reactive oxygen species (ROS) production and damage, furthermore, activates mitochondrial biogenesis and lipogenesis in adipose tissue. The addition of GSPE+DHA-OR to lard resulted in nearly all the effects of DHA-OR and GSPE administered individually, but the combined administration resulted in a more attenuated profile.

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The Contribution of Splanchnic Fat to VLDL Triglyceride Is Greater in Insulin-Resistant Than Insulin-Sensitive Men and Women

Cited by 93 publications

References 46 publications

Mathematical modelling of hepatic lipid metabolism

Mathematical modelling of hepatic lipid metabolism

Menopausal Status and Abdominal Obesity Are Significant Determinants of Hepatic Lipid Metabolism in Women

Omega‐3 polyunsaturated fatty acids and proanthocyanidins improve postprandial metabolic flexibility in rat

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