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Biomedical subjects

Barbara A Gower

Publications and source records attributed to Barbara A Gower.

34 records · Page 2Linked to original sources

Ability of the actiwatch accelerometer to predict free-living energy expenditure in young children.

OBJECTIVE: To determine whether activity counts obtained with the Actiwatch monitor are associated with total expenditure and body composition in young children. RESEARCH METHODS AND PROCEDURES: Actiwatch activity monitors were tested in 29 children 4 to 6 years old under field conditions over eight days. Total energy expenditure (TEE) was assessed with the doubly labeled water (DLW) technique. Correlation analyses were used to identify variables related to energy expenditure and percentage body fat. Multiple linear regression analyses were used to examine the variance in TEE and percentage body fat explained by activity counts after adjusting for relevant covariates. RESULTS: Both average total daily activity counts (658,816 +/- 201,657) and the pattern of activity were highly variable among subjects. TEE was significantly related to lean body mass (r = 0.45) and age (r = 0.48; p < 0.05 for both). Activity counts alone were not associated with TEE. In multiple linear regression analyses, TEE was independently associated with only lean body mass. Percentage fat mass was independently associated with body weight, being a girl, and being white, but not with average total activity counts. DISCUSSION: Activity counts obtained with the Actiwatch under free-living conditions do not reflect TEE in 4- to 6-year-old children and are not correlated with percentage fat mass. Therefore, average total activity counts obtained with the Actiwatch may be of limited value in identifying children at risk for becoming obese.

Adipose Tissue↗

Comparison of self-reported with objectively assessed energy expenditure in black and white women before and after weight loss.

BACKGROUND: Weight maintenance is less successful in black women than in white women after weight loss. OBJECTIVE: We compared objectively assessed total energy expenditure (TEE) with estimates of energy expenditure (EE) from self-reported physical activity (PA) in overweight black and white women before and after weight loss. We also compared those values with values in never-overweight control subjects. DESIGN: A total of 20 white and 21 black premenopausal women were evaluated while overweight and weight reduced; 20 white and 14 black control subjects (matched with women in the weight-reduced state) were evaluated once. Weight loss of >/=10 kg was achieved by energy restriction in the overweight subjects. The evaluations were as follows: body composition (dual-energy X-ray absorptiometry), free-living TEE (doubly labeled water), Tecumseh Occupational Activity Questionnaire, Minnesota Leisure Time PA Questionnaire, and Baecke Activity Questionnaire. RESULTS: Questionnaire estimates of TEE were overestimated when compared with TEE (P < 0.001). Overweight women overestimated TEE 49% more than did never-overweight control subjects. After weight loss, white women reduced overestimation of EE 48% (P < 0.05), so that their overestimation of EE was not different from that of black and white control subjects. Black women overestimated to the same extent both before and after weight loss. CONCLUSIONS: Premenopausal women overestimate PA estimates on questionnaires. Overestimation of PA in weight-reduced black women is greater than in weight-reduced white women and never-overweight black and white women.

Adult↗

Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long-chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians.

BACKGROUND: Indian Asians in Western countries have a higher rate of coronary artery disease than do the indigenous white populations, and this higher rate may be influenced by a dietary imbalance of n-6 and n-3 polyunsaturated fatty acids (PUFAs). OBJECTIVE: The objective of the study was to test the hypothesis that a high background dietary intake of n-6 PUFA attenuates the effects of fish-oil supplementation on insulin sensitivity and associated blood lipids of the metabolic syndrome. DESIGN: Twenty-nine Indian Asian men were recruited to participate in a 12-wk dietary intervention trial. Volunteers were randomly assigned to receive either a moderate or a high n-6 PUFA diet featuring modified oils and spreads over a 6-wk period. After this 6-wk period, both groups were supplemented with 4.0 g fish oil/d (2.5 g eicosapentaenoic acid + docosahexaenoic acid) for an additional 6 wk in combination with the dietary treatment. Volunteers participated in a postprandial study and an insulin sensitivity test after the 6-wk dietary intervention and again after the fish-oil supplementation period. RESULTS: There was no significant time x treatment interaction for blood lipids or insulin action after dietary intervention with the moderate or high n-6 PUFA diets in combination with fish oil. After the 6-wk period of fish oil supplementation, fasting and postprandial plasma triacylglycerol concentrations decreased significantly. CONCLUSION: The background dietary n-6 PUFA concentration did not modulate the effect of fish-oil supplementation on blood lipids or measures of insulin sensitivity in this ethnic group.

Adult↗

Dietary phytoestrogens increase metabolic resistance (cold tolerance) in long-chain acyl-CoA dehydrogenase-deficient mice.

We evaluated the role of dietary phytoestrogens (PE) in the disease phenotype of cold intolerance that characterizes long-chain acyl-CoA dehydrogenase-deficient (LCAD-/-) mice, a model of inborn errors of mitochondrial fatty acid beta-oxidation. Male LCAD-/- mice were fed a standard diet containing endogenous PE, a PE-free diet, or a PE-free diet that was supplemented with genistein (250 microg/g diet). The standard diet did not restore complete cold tolerance, but it provided more resistance (P = 0.004) to cold challenge than the PE-free diet. There was a nonsignificant difference (P < 0.07) between LCAD-/- mice fed the genistein-supplemented diet and those fed the PE-free diet. There were no differences in end-point serum glucose concentrations among the 3 groups. Serum FFA were decreased in LCAD-/- mice fed the standard diet compared with those fed the PE-free diet (P = 0.005) and the diet supplemented with genistein (P < 0.001). Serum triglyceride concentrations were greater (P < 0.05) only in LCAD-/- mice fed the genistein-supplemented diet than those fed the standard diet. These results demonstrate the beneficial effects of dietary PE on metabolic tolerance in LCAD-/- mice. Furthermore, they suggest changes that could improve pediatric formula constituents, especially with regard to management of children with inborn errors of fatty acid oxidation.

Acclimatization↗

HIV protease inhibitor ritonavir induces lipoatrophy in male mice.

We investigated the effects of the HIV protease inhibitor ritonavir on body composition, serum lipids, and gene expression in C57BL/6 mice. Dual-energy X-ray absorptiometry measurements in ritonavir-treated male mice revealed whole-body lipoatrophy. In female mice fat reduction was restricted to the gonadal depot. A histopathological analysis showed no visible abnormalities in liver or adipose tissue from ritonavir-treated mice, although adipocytes were significantly smaller in diameter. Serum triglyceride levels were increased in ritonavir-treated male mice. Ritonavir was coadministered with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist gemfibrozil and the PPARgamma agonist rosiglitazone for 8 weeks. Neither drug alleviated the hypertriglyceridemia or lipoatrophy in ritonavir-treated male mice. Rather, gemfibrozil exacerbated the lipoatrophy. Ritonavir reduced basal expression of two PPARalpha target genes in liver, as well as the PPARgamma target gene phosphoenolpyruvate carboxykinase (PEPCK) in adipose tissues. Ritonavir partially inhibited induction of PPAR target genes by gemfibrozil and rosiglitazone. Gemfibrozil induced expression of fatty acid oxidation genes in liver, and this induction was less substantial when ritonavir was coadministered. Similarly, rosiglitazone induced expression of uncoupling protein-1, uncoupling protein-2, and PEPCK in adipose tissues, and this effect was partially inhibited by ritonavir. Thus, the effects of ritonavir on serum triglycerides and body composition may be due, at least in part, to an inhibition of PPAR function.

Animals↗

Gender differences in resistance-training-induced myofiber hypertrophy among older adults.

We tested the hypothesis that older men (n = 9, 69 +/- 2 years) would experience greater resistance-training-induced myofiber hypertrophy than older women (n = 5, 66 +/- 1 years) following knee extensor training 3 days per week at 65-80% of one-repetition maximum for 26 weeks. Vastus lateralis biopsies were analyzed for myofiber areas, myosin heavy chain isoform distribution, and levels of mRNA for insulin-like growth factor 1 (IGF-1), IGFR1, and myogenin. Gender x Training interactions (p <.05) indicate greater myofiber hypertrophy for all three primary fiber types (I, IIa, IIx) and enhanced one-repetition maximum strength gain in men compared with women (p <.05). Covarying for serum IGF-1, dehydroepiandrosterone sulfate, or each muscle mRNA did not negate these interactions. In both genders, type IIx myofiber area distribution and myosin heavy chain type IIx distribution decreased with a concomitant increase in type IIa myofiber area distribution (p <.05). In summary, gender differences in load-induced myofiber hypertrophy among older adults cannot be explained by levels of circulating IGF-1 or dehydroepiandrosterone sulfate, or by expression of the myogenic transcripts examined.

Aged↗

Influence of family history of type 2 diabetes on insulin sensitivity in prepubertal children.

The objective of this study was to examine the influence of positive family history (FH) of type 2 diabetes (T2D) on aspects of insulin resistance in prepubertal children. Twenty-one children (Tanner stage I or II) with a positive FH were compared with children with no FH. FH was defined by presence of T2D in a parent or grandparent as assessed by interview. The two groups of children were matched for age, gender, Tanner stage, ethnicity, geographical location, and body fat mass using a pair-matched design. These 21 pairs of children included Caucasian, African American, and Hispanic children who were studied either in Birmingham, Alabama, or Los Angeles, California, using similar techniques. Insulin sensitivity (S(I)) and the acute insulin response to glucose (AIR) were determined by an iv glucose tolerance test and minimal modeling, and body composition was determined by dual-energy x-ray absorptiometry. There were no significant differences in fasting glucose or insulin, S(I), AIR, the disposition index (product of S(I) and AIR), or body composition between children with a FH vs. those without a FH of T2D, and there were no significant differences in these parameters when the data were analyzed separately in each ethnic group. In conclusion, a positive FH for T2D does not seem to have any significant effect on insulin sensitivity, as assessed by the minimal model and associated risk factors for T2D in young children.

Adipose Tissue↗

Relationship between serum leptin concentration and low-density muscle in postmenopausal women.

The accretion of fat within skeletal muscle has been associated with metabolic abnormalities. Leptin increases muscle fatty acid oxidation and triglyceride hydrolysis. Therefore, leptin concentrations may affect muscle fat content. The objective of this study was to determine if serum leptin concentrations were associated with im lipid content, as reflected in the mid-thigh low-density skeletal muscle area (LDMA). In addition, we evaluated whether hormone replacement therapy (HRT) or ethnicity affected this relationship. Our study population consisted of 80 postmenopausal women aged 45-55 yr, (72 Caucasian and 8 African-American). Both HRT users (n = 50) and nonusers (n = 30) were recruited. Total fat mass was estimated using total body dual-energy x-ray absorptiometry. Fat and muscle areas at the mid-thigh were measured using computed tomography scanning. Results showed that, after adjusting for total fat mass, higher-density muscle area, and ethnicity, higher serum leptin concentration was associated with lower LDMA (P < 0.05). African-American women had greater LDMA than Caucasian women, after controlling for leptin concentration (P < 0.05). Use of HRT did not significantly influence LDMA. These results support the hypothesis that leptin decreases skeletal muscle lipid content, promoting lipid oxidation.

Black People↗

Using genetic admixture to explain racial differences in insulin-related phenotypes.

Documented differences in measures of insulin secretion and action between African Americans and European Americans may be due to either genetic or environmental factors. This study used genetic admixture (ADM), determined from approximately 20 ancestry informative markers, and a questionnaire designed to assess socioeconomic status (SES) to examine potential genetic and environmental contributions to minimal model-derived measures of insulin sensitivity (S(I)), fasting insulin, and the acute insulin response to glucose (AIR(g)) in 125 children residing in Birmingham, Alabama. The study was longitudinal in design and yielded multiple outcome measures on each subject. Mixed models analysis was used to determine if ADM and SES were independently related to S(I), fasting insulin, and AIR(g) after adjusting for confounding factors (pubertal status, adiposity, age) and for repeated testing of individuals. In this cohort, African ADM ranged from 0% (individuals with no markers reflecting African ancestry) to 100% (individuals with all 20 markers reflecting African ancestry). Results indicated that ADM was independently related to S(I) (P < 0.001) and fasting insulin (P < 0.01), with individuals having greater African ADM having a lower S(I) and a higher fasting insulin concentration. Both ADM (P < 0.001) and SES (P < 0.05) were independently related to AIR(g); children with greater African ADM or lower SES had a higher AIR(g), even after adjusting for S(I). These observations suggest that use of ADM can replace assignment of individuals to categorical racial groups; that lower S(I) and higher fasting insulin among African Americans compared with European Americans may have a genetic basis; and that higher AIR(g) among African Americans may be due to both genetic factors and to environmental factors that remain to be identified.

Adipose Tissue↗

Evaluation of liver fatty acid oxidation in the leptin-deficient obese mouse.

We hypothesized that liver fatty acid oxidation (FAO) is compromised in the leptin-deficient obese (Lep(ob)/Lep(ob)) mouse model, and that this would be further challenged when these mice were fed a high-fat diet. Obese mice had a 3.8-fold increased body fat content and a 9-fold increased liver fat content as compared to control mice when both groups were fed a low-fat diet. The expression of liver FAO enzymes, carnitine palmitoyltransferase-1a, long-chain acyl-CoA dehydrogenase, medium-chain acyl-CoA dehydrogenase, and short-chain acyl-CoA dehydrogenase, was not affected in obese mice as compared to controls on either a low-fat or a high-fat diet. The expression of very-long-chain acyl-CoA dehydrogenase was elevated in obese mice on the control diet, as compared to control mice. For all measures evaluated, increasing the level of fat in the diet had a smaller effect than leptin deficiency. In summary, despite obese mice having an excess of fat available for mitochondrial beta-oxidation in liver, overall energy balance appeared to dictate that the net liver FAO remained at control levels.

Acyl-CoA Dehydrogenase↗

Effect of changes in fat distribution on the rates of change of insulin response in children.

OBJECTIVE: To develop mixed models for examining longitudinal associations between rates of change in visceral, subcutaneous abdominal, and total body fat with rates of change in fasting insulin (FI) and insulin sensitivity (SI) over 3 years in children. RESEARCH METHODS AND PROCEDURES: Seventy-seven children (mean age, 8.3 years at baseline) from Birmingham, Alabama, with three or more annual measures of FI and SI were included. Abdominal fat was measured by computed tomography, and total body fat and lean tissue mass were measured by DXA. Mixed models examined the longitudinal associations between the baseline level/rate of change of different fat compartments and the rate of change in FI or SI. RESULTS: An annual increase of approximately 5% in FI was associated with 1 cm(2)/yr of visceral fat gain per year (p < 0.05), independent of subcutaneous abdominal fat. A 1-cm(2) difference in initial subcutaneous abdominal fat was associated with an approximately 0.2% increase per year in FI (p < 0.02), independent of visceral fat. None of the rates of change in any of the fat measures was associated with the rate of change of SI. DISCUSSION: The rate of change in visceral fat was positively associated with the rate of change in FI, independent of increasing subcutaneous abdominal fat; however, subcutaneous abdominal fat may be more predictive of the rate of change of FI than visceral or total fat. Therefore, growth-related increases in abdominal fat, particularly subcutaneous abdominal fat, may contribute to accelerating increases in FI, but have no effect on SI.

Absorptiometry, Photon↗

Estradiol may limit lipid oxidation via Cpt 1 expression and hormonal mechanisms.

OBJECTIVE: Evidence indicates that estrogen depresses hepatic lipid oxidation. We tested the hypothesis that estradiol (E(2)) treatment depresses transcription of carnitine palmitoyltransferase-1 (Cpt 1) mRNA and increases adiposity. RESEARCH METHODS AND PROCEDURES: Six ovariectomized female rats were given a subcutaneous pellet of E(2) (5 mg/d), and six were given placebo. Rats were pair-fed by group for 18 days. Body composition was assessed chemically: mRNA for liver Cpt 1, adipose tissue uncoupling protein-2 (Ucp 2), and quadriceps Ucp 3 by Northern analysis; serum glucose, triglycerides (TGs), and free fatty acids by standard techniques; and serum insulin and glucagon by radioimmunoassay. RESULTS: E(2)-treated rats lost more weight than placebo-treated rats (37.3 +/- 6.0 vs. 16.2 +/- 2.6 g, p < 0.01), but did not differ in final carcass composition (adjusted for eviscerated body mass). E(2)-treated rats had lower liver Cpt 1 (p < 0.001) and skeletal muscle Ucp 3 (p < 0.05) mRNA and lower concentrations of glucose, glucagon, and free fatty acids (p < 0.05). E(2)-treated rats tended to have higher insulin (p = -0.067) and TG (p = 0.097). TG tended to be correlated with Cpt 1 mRNA (r = -0.56 and p = 0.07). DISCUSSION: These results suggest that, although E(2) is likely to suppress lipid oxidation and promote TG synthesis, these effects are not manifested in a relative increase in carcass adiposity after 18 days of treatment, at least under conditions of negative energy balance. The possible role of E(2)-mediated changes in insulin and glucagon secretion on hepatic substrate metabolism warrants further study.

Animals↗

Fat distribution and insulin sensitivity in postmenopausal women: influence of hormone replacement.

OBJECTIVE: To examine cross-sectionally the influence of hormone replacement therapy (HRT) on the relationship between body composition and insulin sensitivity (Si). RESEARCH METHODS AND PROCEDURES: Subjects were 57 early postmenopausal white women, 33 receiving HRT and 24 controls. Body composition was estimated using DXA and computed tomography scans at the abdomen and mid-thigh. Si was assessed by a frequently sampled intravenous glucose tolerance test with minimal model analysis. RESULTS: Compared with nonusers, HRT users had lower visceral adipose tissue, fasting serum glucose, and fasting insulin. Total body fat and unadjusted Si did not differ between groups. Visceral adipose tissue mass (VATM) was the only body-fat compartment significantly associated with Si (r(2) = 0.43, p < 0.0001) in a model including total-body fat, upper-trunk fat, subcutaneous abdominal fat mass, leg fat, and mid-thigh low-density lean tissue. Lean body mass was positively correlated with Si among HRT users and tended to be negatively correlated among nonusers. HRT status also affected the relationship between VATM and Si such that, relative to nonusers, HRT users had lower Si across lower VATM levels, but higher Si across higher VATM. DISCUSSION: These results suggest that in postmenopausal women, VATM is uniquely related to Si. HRT affects the relationship between VATM and Si and between lean body mass and Si. These interactions should be considered in future studies.

Absorptiometry, Photon↗

Effects of weight loss on changes in insulin sensitivity and lipid concentrations in premenopausal African American and white women.

BACKGROUND: Few studies have tested the hypothesis that changes in disease risk factors are more closely associated with changes in visceral fat than with changes in other adipose tissue depots, particularly in subjects with different ethnic or racial backgrounds. OBJECTIVE: We describe changes in triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, insulin sensitivity (S(i)), visceral fat, and subcutaneous abdominal adipose tissue (SAAT) with weight loss in premenopausal, overweight [body mass index (in kg/m(2)): 27-30], African American (n = 19) and white (n = 18) women. DESIGN: Assessments were performed before and after diet-induced weight loss to a BMI < 25. Body composition and body fat distribution were assessed with dual-energy X-ray absorptiometry and computed tomography, respectively; S(i) was assessed with an intravenous-glucose-tolerance test and minimal modeling. RESULTS: White women lost significantly more visceral fat and less SAAT than did African American women despite similar weight losses (approximately 13 kg). Mixed-model analysis indicated significant effects of time (ie, weight loss) on S(i), triacylglycerol, HDL cholesterol, and LDL cholesterol and of race on triacylglycerol. Time x race interaction terms were not significant. After adjustment for either total body or visceral fat, time was not related to any outcome variable; however, race remained significantly related to triacylglycerol. CONCLUSIONS: With weight loss, moderately overweight African American and white women experienced significant improvements in S(i) and lipids. The beneficial effects of weight loss did not differ with race and could not be attributed to a specific body fat depot. Lower triacylglycerol concentrations among African American women are independent of both obesity status and body fat distribution.

Abdomen↗

Insulin sensitivity and blood pressure in black and white children.

Although insulin sensitivity is correlated with high blood pressure in adults, it is unclear whether such a relationship exists in children across ethnic groups. Therefore, the aims of the study were to establish (1) if body composition and insulin sensitivity were related to blood pressure in children, and (2) if any differences in blood pressure between white and black children were explained by body composition and/or insulin sensitivity. Insulin sensitivity and the acute insulin response were established by the minimal model and body composition by dual-energy X-ray absorptiometry. Blood pressure was recorded in the supine position. Body composition, fasting insulin (P<0.01), and the acute insulin response (P<0.05) were positively related to systolic blood pressure but not to diastolic blood pressure, and insulin sensitivity (P<0.001) was negatively related to systolic blood pressure but not to diastolic blood pressure. Insulin sensitivity was negatively associated with systolic and diastolic blood pressure after adjustment for body composition (P<0.01). Black children had higher systolic (110+/-9.2 versus 105+/-8.5 mm Hg, P=0.01) and diastolic (59+/-7.0 versus 54+/-8.0 mm Hg, P<0.01) blood pressure than did white children. The ethnic difference in blood pressure was not explained by body composition, fasting insulin, acute insulin response, or insulin sensitivity. In conclusion, the relationship between insulin sensitivity and systolic blood pressure is evident early in life. Black ethnicity and low insulin sensitivity contribute independently to higher blood pressure in children.

Analysis of Variance↗

Contribution of insulin secretion and clearance to glucose-induced insulin concentration in african-american and caucasian children.

Relative to Caucasians (C), African-American (AA) children and adults have lower indices of insulin sensitivity (S(i)) and a higher acute insulin response to glucose (AIR(g)). Among AA children, AIR(g) is greater than that which would be predicted based on lower S(i). The objectives of the present study were 1) to determine whether insulin secretory parameters differ in AA vs. C children and adolescents using C-peptide modeling, 2) to determine whether hepatic insulin extraction differs with ethnicity/race using the C-peptide to insulin molar ratio, and 3) to determine whether the relatively greater AIR(g) among African-Americans is due to greater insulin secretion or lesser clearance. Subjects (n = 76) were AA and C children (mean age, approximately 11 yr). A 3-h tolbutamide-modified iv glucose tolerance test and minimal modeling were used to determine S(i) and AIR(g). First phase C-peptide/insulin secretion and basal, first, and second phase beta-cell sensitivity to glucose were determined using C-peptide modeling with standard kinetic parameters developed in adults. The incremental C-peptide to insulin molar ratio over the 3-h test period, an index of hepatic insulin extraction, was calculated with the trapezoidal method. S(i) was lower and AIR(g) was higher in AA vs. C children. First phase C-peptide/insulin secretion and first phase beta-cell sensitivity to glucose were approximately 2-fold greater in AA vs. C children (P < 0.001); there were no between-group differences in basal or second phase beta-cell sensitivity to glucose. Hepatic insulin extraction was lower in AA vs. C (3.77 +/- 1.78% vs. 5.99 +/- 2.18%; P < 0.001). Multiple linear regression modeling indicated that first phase C-peptide/insulin secretion and hepatic insulin extraction contributed independently to AIR(g); however, it was only first phase C-peptide/insulin secretion that explained the significant independent contribution of ethnicity/race to AIR(g) after adjusting for S(i). The results of this study suggest that greater AIR(g) among AA is due to both greater insulin secretion and lesser hepatic insulin extraction, and that AIR(g) above that predicted based on lower S(i) is due to greater insulin secretion. The insulin secretion data await verification that the kinetic parameters used apply to children and AA.

Adolescent↗