Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial.

Abstract

OBJECTIVES: To determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (S(I)). METHODS: Forty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). S(I) was measured with an intravenous glucose tolerance test. RESULTS: Over three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying S(I) (P<0.05 for both). CONCLUSIONS: Based on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in S(I). TRIAL REGISTRATION: ClinicalTrials.gov NCT00099151.

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Citation

Published Version (Please cite this version)

10.1371/journal.pone.0028190

Publication Info

Huffman, Kim M, Leanne M Redman, Lawrence R Landerman, Carl F Pieper, Robert D Stevens, Michael J Muehlbauer, Brett R Wenner, James R Bain, et al. (2012). Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial. PLoS One, 7(4). p. e28190. 10.1371/journal.pone.0028190 Retrieved from https://hdl.handle.net/10161/10872.

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Scholars@Duke

Huffman

Kim Marie Huffman

Associate Professor of Medicine

Determining the role of physical activity in modulating health outcomes (cardiovascular disease risk) in persons with rheumatologic diseases (rheumatoid arthritis, gout, osteoarthritis)

Integrating clinical rheumatology, basic immunology, metabolism, and exercise science in order to reduce morbidity in individuals with arthritis

Evaluating relationships between circulating and intra-muscular metabolic intermediates and insulin resistance in sedentary as well as individuals engaging in regular exercise

Addressing the role of physical activity in modulating inflammation, metabolism, and functional health in aging populations

Stevens

Robert David Stevens

Adjunct Assistant Professor of Medicine
Bain

James R. Bain

Professor in Medicine
Kraus

Virginia Byers Kraus

Mary Bernheim Distinguished Professor of Medicine

Virginia Byers Kraus, MD, PhD, is the Mary Bernheim Distinguished Professor of Medicine, Professor of Orthopaedic Surgery, Professor of Pathology and a faculty member of the Duke Molecular Physiology Institute in the Duke University School of Medicine. She is a practicing Rheumatologist with over 30 years’ experience in translational musculoskeletal research focusing on osteoarthritis, the most common of all arthritides. She trained at Brown University (ScB 1979), Duke University (MD 1982, PhD 1993) and the Duke University School of Medicine (Residency in Internal Medicine and Fellowship in Rheumatology). Her career has focused on elucidating osteoarthritis pathogenesis and translational research into the discovery and validation of biomarkers for early osteoarthritis detection, prediction of progression, monitoring of disease status, and facilitation of therapeutic developments. She is co-PI of the Foundation for NIH Biomarkers Consortium Osteoarthritis project. Trained as a molecular biologist and a Rheumatologist, she endeavors to study disease from bedside to bench.

Newgard

Christopher Bang Newgard

W. David and Sarah W. Stedman Distinguished Professor of Nutrition in the School of Medicine

Over its 16 year history, our laboratory has investigated mechanisms of metabolic regulation and fuel homeostasis in mammalian systems. Major projects include: 1) Mechanisms involved in regulation of insulin secretion from pancreatic islet β-cells by glucose and other metabolic fuels; 2) Development of methods for protection of β-cells against immune-mediated damage; 3) Studies on spatial organization and regulation of systems controlling hepatic glucose balance; 4) Studies on the mechanisms involved in lipid-induced impairment of insulin secretion and action in diabetes.

Kraus

William Erle Kraus

Richard and Pat Johnson University Distinguished Professor

My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation.  My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I practice as a preventive cardiologist with a focus on cardiometabolic risk and exercise physiology for older athletes.  My research space has both a basic wet laboratory component and a human integrative physiology one.

One focus of our work is an integrative physiologic examination of exercise effects in human subjects in clinical studies of exercise training in normal individuals, in individuals at risk of disease (such as pre-diabetes and metabolic syndrome; STRRIDE), and in individuals with disease (such as coronary heart disease, congestive heart failure and cancer).

A second focus of my research group is exploration of genetic determinates of disease risk in human subjects.  We conduct studies of early onset cardiovascular disease (GENECARD; CATHGEN), congestive heart failure (HF-ACTION), peripheral arterial disease (AMNESTI), and metabolic syndrome.  We are exploring analytic models of predicting disease risk using established and innovative statistical methodology.

A third focus of my group’s work is to understand the cellular signaling mechanisms underlying the normal adaptive responses of skeletal muscle to physiologic stimuli, such as occur in exercise conditioning, and to understand the abnormal maladaptive responses that occur in response to pathophysiologic stimuli, such as occur in congestive heart failure, aging and prolonged exposure to microgravity.

Recently we have begun to investigate interactions of genes and lifestyle interventions on cardiometabolic outcomes.  We have experience with clinical lifestyle intervention studies, particularly the contributions of genetic variants to interventions responses.  We call this Lifestyle Medicopharmacogenetics.

KEY WORDS:

exercise, skeletal muscle, energy metabolism, cell signaling, gene expression, cell stretch, heart failure, aging, spaceflight, human genetics, early onset cardiovascular disease, lifestyle medicine


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