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

ABSTRACT: BACKGROUND: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. METHODS AND RESULTS: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<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 VLDL2- 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 (rs=-0.49, P=0.006), de novo lipogenesis (rs=0.55, P=0.003), and desaturation (rs=0.48, P=0.012) were closely correlated with abdominal obesity-driven large VLDL-triglyceride secretion rate. CONCLUSIONS: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.

SUBMITTER: Hodson L

PROVIDER: S-EPMC4845132 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Hodson Leanne L Banerjee Rajarshi R Rial Belén B Arlt Wiebke W Adiels Martin M Boren Jan J Marinou Kyriakoula K Fisher Ciaran C Mostad Ingrid L IL Stratton Irene M IM Barrett P Hugh R PH Chan Dick C DC Watts Gerald F GF Harnden Karin K Karpe Fredrik F Fielding Barbara A BA

Journal of the American Heart Association 20151002 10

<h4>Background</h4>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.<h4>Methods and results</h4>We used a combination of stable isotope tracer techniques to investigate ...[more]

PMID: 26432801

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Project description:BackgroundStudies examining the relationship between obesity and female-specific cancers have been mainly conducted in Western populations. We aimed to investigate the risk of female-specific cancers according to obesity and menopausal status using a nationwide cohort in Korea.MethodsWe identified 2,708,938 women from the National Health Insurance Service cohort, and obtained baseline body mass index (BMI), waist circumference (WC), and other healthcare data, measured and collected during a health examinations and cancer-screening survey. By setting a normal weight/WC group (BMI, 18•5-22•9 kg/m2 or WC, 80•0-84•9 cm) as the reference, we conducted multivariate analyses using the Cox proportional hazard model to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for each cancer.FindingsThe total follow-up duration was 22389854•63 person-years. In post-menopausal women, the risk of breast, endometrial, and ovarian cancers significantly increased as the BMI classification level increased from normal to class II obesity (aHRs [95% CIs], 1•49 [1•38-1.61], 2•11 [1•81-2•46], and 1•38 [1•20-1•58], respectively). The risk of breast and endometrial cancers also increased as the WC classification increased from < 75•0 to ≥ 95•0 cm. With a WC of 80•0-84•9 cm as the reference, the lowest risk of breast and endometrial cancers was observed in WC < 75•0 cm (aHRs [95% CIs], 0•85 [0•81-0•89] and 0•75 [0•67-0•84], respectively) while the highest risk was observed in WC ≥ 95•0 cm (aHRs [95% CIs], 1•19 [1•10-1•29] and 1•56 [1•33-1•82], respectively). In pre-menopausal women, the risk of breast cancer significantly decreased in those with class I and II obesity compared to those with normal BMI (aHRs [95% CIs], 0•96 [0•92-0•999] and 0•89 [0•81-0•97], respectively), whereas the trends of endometrial and ovarian cancer incidence in pre-menopausal women were similar to those observed in post-menopausal women. For cervical cancer, only class II obesity was significantly associated with increased risks in both post-menopausal and pre-menopausal women (aHRs [95% CIs], 1•18 [1•01-1•39] and 1•27 [1•02-1•57], respectively).InterpretationIn this large population-based cohort study in Korean women, we observed that the impact of obesity on the development of female-specific cancers differs according to the malignancy type and menopausal status. Similar trends were observed between Korean and Western women.FundingThe Korea Health Industry Development Institute (no. HI16C2037).

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

Publications

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

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