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Stolzenberg-Solomon R.Z.,U.S. National Institutes of Health | Falk R.T.,U.S. National Institutes of Health | Stanczyk F.,Mission Research | Hoover R.N.,U.S. National Institutes of Health | And 8 more authors.
Breast Cancer Research | Year: 2012

Introduction: Changes in sex hormones with weight loss might have implications for breast cancer prevention but have not been examined extensively, particularly in African-American (AA) women.Methods: We conducted a prospective study of 278 overweight/obese postmenopausal women (38% AA) not taking hormone therapy within the Weight Loss Maintenance Trial. All participants lost at least 4 kg after a 6-month weight-loss phase and attempted to maintain weight loss during the subsequent 12 months. We evaluated the percentage changes in estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) using generalized estimating equations.Results: In all study phases, AA women had higher levels of estrogen and testosterone concentrations, independent of adiposity. On average, participants lost 7.7 kg during the weight-loss phase, and concentrations of estrone (-5.7%, P = 0.006), estradiol (-9.9%, P <0.001), free estradiol (-13.4%, P <0.0001), and free testosterone (-9.9%, P <0.0001) decreased, while the SHBG concentration (16.2%, P <0.001) increased. Weight change did not significantly affect total testosterone or other androgen concentrations. Compared with non-AA women, AA women experienced less change in estrogens per kilogram of weight change (that is, per 1 kg weight loss: estrone, -0.6% vs. -1.2%, P-interaction = 0.10; estradiol, -1.1% vs. -1.9%, P-interaction = 0.04; SHBG, 0.9% vs. 1.6%, P-interaction = 0.006; free estradiol, -1.4% vs. -2.1%, P-interaction = 0.01).Conclusion: To the best of our knowledge this is the first study to examine and compare the effects of intentional weight loss and maintenance on a panel of sex hormones in AA women and non-AA women. Although speculative, these data suggest hormonal differences may contribute to different racial patterns of breast cancer incidence and mortality and encourage further investigations to understand the long-term effects of weight loss on sex hormones in obese postmenopausal women.Trial Registration: ClinicalTrials.gov: NCT00054925. © 2012 Stolzenberg-Solomon et al.; licensee BioMed Central Ltd.

Malloy C.R.,Advanced Imaging Research Center | Malloy C.R.,University of Texas Southwestern Medical Center | Newgard C.B.,Sarah edman Nutrition And Metabolism Center | Podgoreanu M.V.,Duke University
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2010

Purpose of review: Profound abnormalities in myocardial energy metabolism occur in heart failure and correlate with clinical symptoms and survival. Available comprehensive human metabolic data come from small studies, enrolling patients across heart failure causes, at different disease stages, and using different methodologies, and is often contradictory. Remaining fundamental gaps in knowledge include whether observed shifts in cardiac substrate utilization are adaptive or maladaptive, causal or an epiphenomenon of heart failure. Recent findings: Recent studies have characterized the temporal changes in myocardial substrate metabolism involved in progression of heart failure, the role of insulin resistance, and the mechanisms of mitochondrial dysfunction in heart failure. The concept of metabolic inflexibility has been proposed to explain the lack of energetic and mechanical reserve in the failing heart. Summary: Despite current therapies, which provide substantial benefits to patients, heart failure remains a progressive disease, and new approaches to treatment are necessary. Developing metabolic interventions would be facilitated by systems-level integration of current knowledge on myocardial metabolic control. Although preliminary evidence suggests that metabolic modulators inducing a shift towards carbohydrate utilization seem generally beneficial in the failing heart, such interventions should be matched to the stage of metabolic deregulation in the progression of heart failure. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Corsino L.,Duke University | Corsino L.,Sarah edman Nutrition And Metabolism Center | Batch B.C.,Duke University | Batch B.C.,Sarah edman Nutrition And Metabolism Center | And 5 more authors.
Ethnicity and Disease | Year: 2012

Objective: To pilot test a culturally adapted behavioral weight loss intervention in obese and overweight Latino adults. Design: Pilot study. Setting: Latino community organization in Durham, North Carolina. Participants: Overweight and obese, selfidentified Latinos ≥18 years old. Intervention: Intervention consisted of 20 weekly group sessions (90-120 minutes each) incorporating motivational interviewing techniques. The intervention goal was weight loss by adopting the Dietary Approach to Stop Hypertension (DASH) dietary pattern, increasing physical activity, and reducing caloric intake. The cultural adaptation included foods and physical activities commonly used in the Latino culture, using a Spanishspeaking interventionist, and conducting the intervention at a local Latino community organization. Main outcome measures: Weight, body mass index (BMI), blood pressure, dietary pattern, and physical activity were measured at baseline and at 20 weeks. Results: A total of 56 participants are included in the final analysis. The average weight loss was 5.1 lbs (95% CI -8.7 to -1.5; P=.006); and there was a reduction in BMI of 1.3 kg/m 2(95% CI -2.2 to -0.5; P=.002) at 20 weeks. Systolic blood pressure decreased by 2.6 mm Hg (95% CI -4.7 to -0.6; P=.013). Conclusion: A culturally adapted behavioral intervention for the treatment of overweight and obesity is potentially effective in a diverse group of Latino adults.

Green M.F.,Sarah edman Nutrition And Metabolism Center | Hirschey M.D.,Sarah edman Nutrition And Metabolism Center | Hirschey M.D.,Duke University
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2013

Eating a "Western diet" high in fat and sugars is associated with accelerated development of age-related metabolic diseases such as obesity, insulin resistance, and diabetes while incidences of these diseases are decreased on a low-calorie diet. The mitochondrial NAD(+)-dependent protein deacetylase SIRT3 has previously been shown to be important in adapting to metabolic stress brought on by fasting and calorie restriction. During times of metabolic stress, SIRT3 is upregulated and maintains homeostasis following nutrient deprivation by turning on pathways such as fatty acid oxidation, antioxidant production, and the urea cycle. New studies now demonstrate that SIRT3 is regulated during nutrient excess. During high-fat diet feeding, SIRT3 is downregulated leading to mitochondrial protein hyperacetylation. The consequence of this hyperacetylation is the accelerated development of metabolic syndrome. Thus, SIRT3 is emerging as an important metabolic sensor working to restore metabolic homeostasis during times of stress. © 2012 The Author. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

Tai E.S.,National University of Singapore | Tan M.L.S.,Singapore Health Services | Stevens R.D.,Sarah edman Nutrition And Metabolism Center | Low Y.L.,Singapore Institute of Clinical Science | And 10 more authors.
Diabetologia | Year: 2010

Aims/hypothesis: Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. Methods: We selected 263 non-obese (BMI approximately 24 kg/m2) Asian-Indian and Chinese men from a large cross-sectional study carried out in Singapore. Individuals taking medication for diabetes or hyperlipidaemia were excluded. Participants were separated into lower and upper tertiles of IR based on HOMA indices of ≥1.06 or ≤1.93, respectively. MS-based metabolic profiling of acylcarnitines, amino acids and organic acids was combined with hormonal and cytokine profiling in all participants. Results: After controlling for BMI, commonly accepted risk factors for IR, including circulating fatty acids and inflammatory cytokines, did not discriminate the upper and lower quartiles of insulin sensitivity in either Asian-Indian or Chinese men. Instead, IR was correlated with increased levels of alanine, proline, valine, leucine/isoleucine, phenylalanine, tyrosine, glutamate/glutamine and ornithine, and a cluster of branched-chain and related amino acids identified by principal components analysis. These changes were not due to increased protein intake by individuals in the upper quartile of IR. Increased abdominal adiposity and leptin, and decreased adiponectin and IGF-binding protein 1 were also correlated with IR. Conclusions/interpretation: These findings demonstrate that perturbations in amino acid homeostasis, but not inflammatory markers or NEFAs, are associated with IR in individuals of relatively low body mass. © 2009 Springer-Verlag.

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