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

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.

Lower resting and total energy expenditure in postmenopausal compared with premenopausal women matched for abdominal obesity.

The menopause is accompanied by increased risk of obesity, altered body fat distribution and decreased skeletal muscle mass. The resulting decrease in RMR should be accompanied by a compensatory change in energy balance to avoid weight gain. We aimed to investigate habitual energy intake and expenditure in pre- and postmenopausal women matched for abdominal obesity. We recruited fifty-one healthy Caucasian women, BMI > 18·5 and <35 kg/m(2), aged 35-45 years (premenopausal, n 26) and 55-65 years (postmenopausal, n 25). Energy intake was measured using 3 d diet diaries and dietary fat quality assessed using adipose tissue fatty acid biomarkers. RMR was measured using indirect calorimetry, and total energy expenditure (TEE) and activity energy expenditure using a combined accelerometer and heart rate monitor. Postmenopausal women had lower RMR and TEE and spent significantly less time undertaking moderate exercise than premenopausal women. Postmenopausal women had a tendency for a lower energy intake, and a similar macronutrient intake but a significantly lower adipose tissue n-6:n-3 ratio (24·6 (se 1·6) v. 37·7 (se 3·1); P < 0·001). The main lifestyle determinant of bone mineral density (which was significantly lower in postmenopausal women) was TEE for premenopausal women, and dietary n-6:n-3 ratio for postmenopausal women. The present results suggest that weight maintenance is achieved in the post- compared with premenopausal status through a combination of reduced energy intake and reduced TEE in a regimen that compromises micronutrient intake and has a negative impact on lean tissue mass. However, lower n-6:n-3 fatty acid intake in postmenopausal women is associated with greater bone mineral density.