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

Abstract

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.

Fruit Fiber Consumption Specifically Improves Liver Health Status in Obese Subjects under Energy Restriction

“…This outcome might be expected, since the AHA diet is specifically based on the AHA guidelines [ 23 ], which focus on cardiovascular care and therefore on lipid profile management. Interestingly, the RESMENA diet had a positive effect on body weight by reducing android fat mass—a body region which has been commonly associated with hepatic steatosis [ 24 ]. On the other hand, current research has focused on identifying biomarkers to predict NASH or NAFLD [ 25 , 26 ].…”

Progression of Metabolic Syndrome Severity During the Menopausal Transition

“…The mechanisms behind the slower rate progression of MetS severity after menopause are unclear but could be related to changes in estrogen levels and related action of adipocytes and hepatic function. 3,25,26 Tepper et al demonstrated that while there is an overall decline in estradiol levels between 6 years before and 1 year after the final menstrual period (when estradiol levels stabilize), the pattern of this decline is variable. In 60% of white and 25% of black women, there is an initial rise in estradiol to 50% above baseline.…”

Fasting Plasma Insulin Concentrations Are Associated With Changes in Hepatic Fatty Acid Synthesis and Partitioning Prior to Changes in Liver Fat Content in Healthy Adults

“…Animal work has suggested DNL FAs exit the liver immediately as VLDL-TG rather than being stored (33). Although evidence for this is sparse in humans (34,35), hepatic DNL has been positively associated with VLDL-TG production rates (11,12).…”

“…Taken together, this may lead to enhanced VLDL-TG production and a net retention of intrahepatocellular TG (4,5). Positive associations between hepatic DNL and VLDL-TG production rates have been reported (11,12).…”