Betty E. Darnell

Resistance Training Conserves Fat-free Mass and Resting Energy Expenditure Following Weight Loss

Objective: To determine what effect diet‐induced ∼12 kg weight loss in combination with exercise training has on body composition and resting energy expenditure (REE) in premenopausal African‐American (AA) and European‐American (EA) women.

Effect of the fat composition of a single meal on the composition and cytotoxic potencies of lipolytically-releasable free fatty acids in postprandial plasma

Ingestion of a meal increases plasma levels of triglyceride (TG)-rich lipoproteins through the secretion of intestine-derived chylomcirons and liver-derived very low density lipoproteins (VLDL). We have determined the effects of the fat composition of a single meal on the composition of TG in TG-rich lipoproteins (VLDL + chylomicrons) and circulating and lipolytically-releasable free fatty acids (FFA) in postprandial (PP) plasma and on the cytotoxic potencies of the lipolytically-released FFA to cultured arterial wall cells. PP lipemia was induced by feeding fasted normolipidemic human subjects with a meal rich in saturated fat (SF) and another meal rich in polyunsaturated fat (PUF), or vice versa; each meal provided 65% of energy as fat, and polyunsaturated to saturated fatty acid ratios (P/S) of the SF and PUF in the meals were 0.40 and 2.49, respectively. The mean P/S of TG in TG-rich lipoproteins (1.43) and circulating FFA (1.46) in 4 h PP plasma of PUF were significantly higher than those in PP plasma of SF (0.44 and 0.59, respectively) in fasting plasma (0.52 and 0.53, respectively). In vitro lipolysis of fasting and PP serum by purified bovine milk lipoprotein lipase (LpL) resulted in a marked (8.8-12.3-fold) increase in the serum FFA level. The P/S of serum FFA in postlipolysis fasting and PP serum were consistently higher than that of FFA or that of TG associated with TG-rich lipoproteins in prelipolysis fasting and PP serum, indicating that polyunsaturated TG in VLDL and/or chylomicrons is more susceptible than saturated TG to lipolysis. When postlipolysis serum was interacted with cultured endothelial cells and mouse peritoneal macrophages (MPM), the lipolytically-released FFA in PP serum of SF and PUF disrupted the barrier function of endothelial cells and were cytotoxic to cultured MPM; FFA in postlipolysis fasting serum was not cytotoxic. FFA in postlipolysis PP serum of PUF were consistently more potent than that in postlipolysis PP serum of SF. Further study showed that all long-chain monounsaturated FFA and polyunsaturated FFA, but not saturated FFA, incorporated into lipoproteins (LDL) were cytotoxic to cultured MPM. In conclusion, despite the generally well-accepted belief that SF is more atherogenic than PUF, the present study provides in vitro evidence that the lipolytic remnant products of TG-rich lipoproteins produced after a meal rich in PUF are more injurious to arterial wall cells than those produced after a meal rich in SF.

Medium Chain Triglyceride Oil Consumption as Part of a Weight Loss Diet Does Not Lead to an Adverse Metabolic Profile When Compared to Olive Oil

Objective: Medium chain triglyceride (MCT) consumption may have a beneficial impact on weight management, however, some studies point to a negative impact of MCT oil consumption on cardiovascular disease risk. This study examined the effects of MCT oil consumption, as part of a weight loss diet, on metabolic risk profile compared to olive oil. Design: Thirty-one men and women, age 19–50 y and body mass index 27–33 kg/m2, completed this randomized, controlled, 16-week weight loss program. Oils were consumed at a level of ∼12% of the subjects’ prescribed energy intakes in the form of muffins and liquid oil. Results: After controlling for body weight, there was a significant effect of time on fasting serum glucose (P = 0.0177) and total cholesterol (P = 0.0386) concentrations, and on diastolic blood pressure (P = 0.0413), with reductions in these variables occurring over time; there was no time-by-diet interaction for any of the parameters studied. Two of the 3 subjects in the MCT oil group with evidence of the metabolic syndrome at baseline did not have metabolic syndrome at endpoint. In the olive oil group, 6 subjects had the metabolic syndrome at baseline; 2 subjects no longer had metabolic syndrome at endpoint, 1 person developed metabolic syndrome, and 4 subjects did not have any change in their metabolic syndrome status. Conclusions: Our results suggest that MCT oil can be incorporated into a weight loss program without fear of adversely affecting metabolic risk factors. Distinction should be made regarding chain length when it comes to discussing the effects of saturated fats on metabolic risk factors.

Fasting and postprandial markers of inflammation in lean and overweight children

BACKGROUND Overweight children have greater circulating concentrations of markers of inflammation (MOI) than do lean children. Whether adiposity influences the postprandial MOI response is unknown. OBJECTIVE We aimed to evaluate the relations of fasting and postprandial MOI with total and regional adiposity and insulin sensitivity in children. DESIGN Fifty-nine children aged 7-12 y were assessed for C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptor-2 (sTNF-R2) in the fasted state and after a mixed meal. Insulin sensitivity, body composition, and abdominal adipose tissue distribution were assessed with a frequently sampled intravenous-glucose-tolerance test, dual-energy X-ray absorptiometry, and computed tomography, respectively. RESULTS Central adipose measures were not independently associated with fasting MOI, although they were independently inversely associated with the postprandial sTNF-R2 response (r = -0.30 to -0.37, P = 0.02-0.006). The inverse association between intraabdominal adipose tissue and the postprandial CRP response was nearly significant (r = -0.27, P = 0.05). Insulin sensitivity was not associated with fasting or postprandial CRP or sTNF-R2; however, there was a positive relation between insulin sensitivity and fasting IL-6 (r = 0.27, P = 0.03), which was attenuated after adjustment for lean body mass (r = 0.25, P = 0.08). CONCLUSIONS Excess adiposity is associated with both fasting and postprandial MOI. The postprandial MOI response may be influenced by central adiposity in children. The positive association of insulin sensitivity with IL-6 warrants further study.

Obesity-related hypertension: Evaluation of the separate effects of energy restriction and weight reduction on hemodynamic and neuroendocrine status☆

PURPOSE Although weight reduction generally lowers blood pressure, it is unclear whether the response is due to concurrent dietary changes or to reduced body mass itself. In this study, the independent effects of energy restriction and weight reduction were examined prospectively in 24 obese, hypertensive, normoglycemic women whose dietary intake was tightly controlled. SUBJECTS AND METHODS Sodium, potassium, and calcium intake, the polyunsaturated/saturated fat ratio, and the proportional composition of carbohydrate, fat, and protein were constant throughout the 5-month protocol. Hemodynamic and neuroendocrine status was evaluated in four 10-day hospital phases: two prior to weight loss (energy balance and then 800-kcal intake), and two after an average loss of 13 kg to normal body weight (800 kcal and then return to energy balance). RESULTS Fasting serum insulin, triiodothyronine:reverse triiodothyronine ratio, resting metabolic rate, and heart rate declined, and sodium and potassium balances were negative during energy restriction. Catecholamines, renin, aldosterone, plasma volume, cardiac output, and blood pressure showed no consistent response to changes in energy intake. By contrast, weight reduction independently lowered blood pressure, plasma volume, cardiac output, and plasma renin activity. Body fat pattern remained unchanged. CONCLUSION These results demonstrate that weight loss has a blood pressure-lowering effect that is distinct from energy restriction and that is related to changes in blood volume and cardiac output.

Physical activity may facilitate diabetes prevention in adolescents.

OBJECTIVE—The aim of this study was to examine the association of physical activity with glucose tolerance and resting energy expenditure (REE) among adolescents. RESEARCH DESIGN AND METHODS—Subjects were 32 male and female adolescents aged 12–18 years. Intravenous glucose tolerance (Kg) and REE were assessed under inpatient conditions after an overnight fast. Kg was determined as the inverse slope of time versus (ln) glucose over minutes 8–19 of an intravenous glucose tolerance test. Physical activity was assessed over 8 days using accelerometry (counts per minute). RESULTS—In multiple linear regression analysis, Kg was positively associated with total physical activity (TPA), moderate physical activity (MPA), and 5-min bouts of MPA. Similarly, REE was positively associated with TPA, MPA, and 5-min bouts of MPA. CONCLUSIONS—In this population, physical activity was positively related to both glucose tolerance and REE. These results suggest that moderate activity may be beneficial in the prevention of diabetes in adolescent populations both through promoting efficient glucose disposal and through increasing energy expenditure.

Vitamin D intake is associated with insulin sensitivity in African American, but not European American, women.

BackgroundThe prevalence of type 2 diabetes is higher among African Americans (AA) vs European Americans (EA), independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women.MethodsSubjects were 115 African American (AA) and 137 European American (EA) healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (SI) with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry.ResultsVitamin D intake was positively associated with SI (standardized β = 0.18, P = 0.05) and inversely associated with HOMA-IR (standardized β = -0.26, P = 0.007) in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized β = 0.03, P = 0.74 and standardized β = 0.02, P = 0.85 for SI and HOMA-IR, respectively). Similar to vitamin D, dietary calcium was associated with SI and HOMA-IR among AA but not EA.ConclusionsThis study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.

Potencies of Lipoproteins in Fasting and Postprandial Plasma to Accept Additional Cholesterol Molecules Released From Cell Membranes

To investigate the role of various lipoproteins in plasma to promote cholesterol efflux from cell membranes, potencies of lipoproteins in normolipidemic fasting and postprandial (PP) plasmas to accept additional cholesterol molecules from cell membranes were determined. We used red blood cells (RBCs) and lipoproteins in fresh blood as donors and acceptors of cell membrane cholesterol, respectively. When fresh fasting plasma (n=24) containing active lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer proteins (CETP) was incubated with a 3-fold excess of autologous RBCs at 37 degrees C for 18 hours, plasma cholesterol levels increased by 19.6% (38.5+/-14.2 mg/dL) owing to an exclusive increase in the CE level. Very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions retained 48.1%, 26.3%, and 25.6% of the net cholesterol mass increase in fasting plasma, resulting in 91%, 8%, and 21% increases in their cholesterol contents, respectively. The PP plasma was 1.3-fold more potent than fasting plasma in promoting cholesterol efflux from RBCs by associating excess cholesterol with chylomicrons, resulting in a 356% increase in the cholesterol content of chylomicrons. These increases in lipoprotein cholesterol content indicate that chylomicrons were about 3.9x, 44x, and 17x more potent than fasting VLDL, LDL, and HDL, respectively, in accepting additional cholesterol molecules released from RBCs. The capacity of PP plasma to promote cholesterol efflux from RBCs was significantly correlated with plasma cholesterol levels (r=0.60, P<0.005), triglycerides (r=0.68, P<0.001), chylomicrons (r=0.90, P<0.001), VLDL (r=0.65, P<0.001), and LDL (r=0.47, P<0.025) but not with the levels of HDL (r= -0.34, P<0.20). In fasting plasma containing a low level of VLDL and HDL, isolated chylomicrons supplemented to the plasma were approximately 9x more potent than HDL in boosting the capacity of plasma to promote cholesterol efflux from RBCs. This study indicates that chylomicrons in PP plasma are the most potent ultimate acceptors of cholesterol released from cell membranes and that a low HDL level is not a factor that limits the ability of PP plasma to promote cholesterol efflux from cell membranes. Our data obtained from an in-vitro system suggest that PP chylomicrons may play a major role in promoting reverse cholesterol transport in vivo, since the transfer of cholesterol from cell membranes to chylomicrons will lead to the rapid removal of this cholesterol by the liver. HDL in vivo may promote reverse cholesterol transport by enhancing the rapid removal of chylomicrons from the circulation, since the rate of clearance of chylomicrons is positively correlated with the HDL level in plasma.

Longitudinal associations of the endocrine environment on fat partitioning in postmenopausal women

Among postmenopausal women, declining estrogen may facilitate fat partitioning from the periphery to the intra‐abdominal space. Furthermore, it has been suggested that excess androgens contribute to a central fat distribution pattern in women. The objective of this longitudinal study was to identify independent associations of the hormone milieu with fat distribution in postmenopausal women. Fifty‐three healthy postmenopausal women, either using or not using hormone replacement therapy (HRT) were evaluated at baseline and 2 years. The main outcomes were intra‐abdominal adipose tissue (IAAT), subcutaneous abdominal adipose tissue, and total thigh fat analyzed by computed tomography scanning and leg fat and total body fat mass measured by dual‐energy X‐ray absorptiometry. Serum estradiol, estrone, estrone sulfate, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate), sex hormone‐binding globulin (SHBG), and cortisol were assessed. On average, in all women combined, IAAT increased by 10% (10.5 cm2) over 2 years (P < 0.05). Among HRT users, estradiol was inversely associated with, and estrone was positively associated with, 2‐year gain in IAAT. Among HRT nonusers, free testosterone was inversely associated with, and SHBG was positively associated with, 2‐year gain in IAAT. These results suggest that in postmenopausal women using HRT, greater circulating estradiol may play an integral role in limiting lipid deposition to the intra‐abdominal cavity, a depot associated with metabolically detrimental attributes. However, a high proportion of weak estrogens may promote fat partitioning to the intra‐abdominal cavity over time. Furthermore, among postmenopausal women not using HRT, greater circulating free testosterone may limit IAAT accrual.

Associations of Free Fatty Acids With Insulin Secretion and Action Among African-American and European-American Girls and Women

Ethnic differences in insulin secretion and action between African Americans (AAs) and European Americans (EAs) may influence mobilization of free fatty acids (FFAs). We tested the hypotheses that FFA concentrations would be associated with measures of insulin secretion and action before and during a glucose challenge test. Subjects were 48 prepubertal girls, 60 premenopausal women, and 46 postmenopausal women. Fasting insulin (insulin0), the acute insulin response to glucose (AIRg), the insulin sensitivity index (SI), basal and nadir FFA (FFA0, FFAnadir), and nadir time (TIMEnadir) were determined during an intravenous glucose tolerance test (IVGTT). Stepwise multiple linear regression (MLR) analysis was conducted to identify associations of FFA0, FFAnadir, and TIMEnadir with ethnicity, age group, insulin measures, indexes of body composition from dual‐energy X‐ray absorptiometry, and measures of fat distribution from computed tomography scan. In this population, insulin0 and AIRg were higher among AAs vs. EAs, whereas SI was lower, independent of age group. MLR analyses indicated that FFA0 was best predicted by lean tissue mass (LTM), leg fat mass, ethnicity (lower in AAs), SI, and insulin0. FFAnadir was best predicted by FFA0, age group, and intra‐abdominal adipose tissue (IAAT). TIMEnadir was best predicted by leg fat mass, AIRg, and SI. In conclusion, indexes of insulin secretion and action were associated with FFA dynamics in healthy girls and women. Lower FFA0 among AAs was independent of insulin0 and SI. Whether lower FFA0 is associated with substrate oxidation or risk for obesity remains to be determined.