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Principal Investigator: DYMPNA GALLAGHER
Organization: COLUMBIA UNIVERSITY HEALTH SCIENCES
Fiscal Year: 2024
Award: $1,209,450
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Obesity is a major contributor to human illness and health care costs by virtue of its functional associations with
type 2 diabetes, hypertension, fatty liver, dyslipidemias, various cancers, degenerative brain disease and, very
recently, contribution to morbidity and mortality associated with SARS-CoV-2 infection. Modest weight loss can
mitigate the severity – or entirely reverse - many of these phenotypes. Maintenance of a 10% reduced body in
obese or lean individuals invokes homeostatic changes in energy expenditure (decreased) and hunger
(increased) that tend to restore body weight. These changes are conveyed by persistent complex molecular-
physiological processes in the brain and autonomic nervous systems, thyroid and leptin axes, skeletal muscle,
and adipose tissue. Individuals differ in the intensity of these responses, perhaps accounting for differences in
long-term success for weight loss maintenance. This study prospectively examines the behavioral and molecular
physiology of these systems following a lifestyle-mediated 10% weight reduction in individuals with overweight
or obesity, and examines the contributions of these factors to amount of weight regain in the one year period
following achievement of the weight reduction during a period of minimum clinical intervention. Our Specific
Experimental Aims are to:
1. Examine the behavioral, metabolic, and environmental impacts on success in sustaining 10% weight loss
by measuring the association of (a) ad lib energy intake (EI), (b) 24h energy expenditure (EE); and (c) the
individual’s food environment at reduced body weight on changes in body weight and fat mass one year
following achievement of 10% weight reduction.
2. Assess the physiology of the weight-reduced state in dynamic circumstances in order to provide predictors
of weight outcome at 12 months after 10% weight loss. EI and EE will be measured: (a) in response to a
single dose of leptin administered after achievement of reduced body weight; (b) 6 months following weight
loss.
3. Generate mechanistically-informed regression equations predicting change in body weight in the 12
months following 10% weight loss. “Endophenotypes” related to EI and EE will be measured in the weight-
reduced state: food-choice task performance associated with food intake and fMRI activity in the dorsal
striatum; sleep/circadian rhythms; skeletal muscle contractile efficiency (in vivo and ex vivo), plasma
metabolomics /exposomics and endocrines, urinary catecholamines, gene expression and epigenetics of
adipose tissue and muscle, and peripheral blood mononuclear cells. These endophenotypes, EI and EE,
will be used to generate predictive equations that will quantify the relative contributions of these factors and
suggest possible interventions to assist in long-term maintenance of reduced body weight.
Terms: <Accounting><Achievement><Achievement Attainment><Adipocytes><Adipose Cell><Adipose tissue><Adult-Onset Diabetes Mellitus><Autonomic nervous system><Autoregulation><Behavioral><Biochemical><Blood Plasma><Body Composition><Body Weight><Body Weight decreased><Body fat><Brain><Brain Diseases><Brain Disorders><Brain Nervous System><COVID-19 infection><COVID-19 virus infection><COVID19 infection><Calibration><Caloric Intake><Cancers><Cardiac Diseases><Cardiac Disorders><Catecholamines><Circadian Rhythms><Clinical><Communities><Complex><Consensus><Corpus Striatum><Corpus striatum structure><Data><Development><Diabetes Mellitus><Dorsal><Dose><Dyslipidemias><Eating><Eating Behavior><Ecological impact><Encephalon><Encephalon Diseases><Endocrine><Energy Expenditure><Energy Intake><Energy Metabolism><Environment><Environmental Impact><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Equation><Expenditure><Fat Cells><Fatty Liver><Fatty Tissue><Food><Food Intake><Functional MRI><Functional Magnetic Resonance Imaging><Gene Expression><Health Care Costs><Health Costs><Healthcare Costs><Heart Diseases><Home environment><Homeostasis><Human><Hunger><Hypertension><Individual><Individual Differences><Intermediary Metabolism><Intervention><Intervention Strategies><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Ketosis-Resistant Diabetes Mellitus><Leanness><Leptin><Life Style><Lifestyle><Lipocytes><Liver Steatosis><Maintenance><Malignant Neoplasms><Malignant Tumor><Math Models><Mature Lipocyte><Mature fat cell><Maturity-Onset Diabetes Mellitus><Measures><Mediating><Medical><Metabolic><Metabolic Processes><Metabolism><Mitochondria><Modern Man><Molecular><Morbidity><Morbidity - disease rate><Muscle><Muscle Tissue><NEMS><NIDDM><Neuroendocrine><Neuroendocrine System><Neurosecretory Systems><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Nyctohemeral Rhythm><Ob Gene Product><Ob Protein><Obese Gene Product><Obese Protein><Obesity><Organism-Level Process><Organismal Process><Outcome><Over weight><Overweight><PBMC><Peptides><Peripheral Blood Mononuclear Cell><Persons><Phenotype><Physiologic><Physiologic Processes><Physiological><Physiological Adaptation><Physiological Homeostasis><Physiological Processes><Physiology><Plasma><Plasma Serum><Procedures><Prospective Studies><Protocol><Protocols documentation><Respiration><Reticuloendothelial System, Serum, Plasma><Role><SARS-CoV-2 infection><SARS-CoV2 infection><Severe acute respiratory syndrome coronavirus 2 infection><Severities><Site><Skeletal Muscle><Sleep><Slow-Onset Diabetes Mellitus><Stable Diabetes Mellitus><Standardization><Striate Body><Striatum><Survey Instrument><Surveys><Sympathins><System><T2 DM><T2D><T2DM><Task Performances><Thinness><Thyroid><Thyroid Gland><Thyroid Head and Neck><Time><Training><Twenty-Four Hour Rhythm><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Voluntary Muscle><Weight><Weight Loss><Weight Reduction><adipose><adiposity><adult onset diabetes><base><bases><body weight loss><caloric dietary content><circadian process><coronavirus disease 2019 infection><corpulence><daily biorhythm><design><designing><developmental><diabetes><endophenotype><energy balance><epigenetically><fMRI><food environment><heart disorder><hepatic steatosis><hepatosteatosis><high blood pressure><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><in vivo><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><instrument><interventional strategy><ketosis resistant diabetes><malignancy><mathematic model><mathematical model><mathematical modeling><maturity onset diabetes><metabolism measurement><metabolomics><metabonomics><mitochondrial><mortality><muscular><nano electromechanical system><nanoelectromechanical system><neoplasm/cancer><novel><nutrition><physiologic model><prospective><recidivism><respiratory mechanism><response><skeletal tissue><social role><striatal><success><type 2 DM><type II DM><type two diabetes><urinary><weight maintenance><weights><white adipose tissue><wt-loss><yellow adipose tissue>