Reduced Carbohydrate Versus Fat in Obese Subjects
Reduced Carbohydrate Versus Fat in Obese Subjects
Popular weight loss strategies often involve reducing an individual's consumption of
 carbohydrates or fat. However, no controlled study has been carried out to evaluate the
 effects of reducing carbohydrate versus fat consumption while keeping the other nutrients at
 standard levels to maintain an individual's weight. Researchers are interested in
 investigating how different restrictions of carbohydrates or fats affect the many processes
 involved in weight loss, including brain activity and blood and brain chemical composition.
Popular weight loss strategies often prescribe a targeted reduction of dietary carbohydrate
 or fat. But surprisingly, no controlled human feeding study has ever investigated the effects
 of a selective reduction of dietary carbohydrate versus fat while keeping the other dietary
 macronutrients at their baseline weight-maintenance values. The present study was designed to
 address this knowledge gap and improve our understanding of how selective reduction of
 dietary fat versus carbohydrate may differentially impact the many feedback control processes
 that act to resist weight loss.

 Objectives:

 - To determine the comparative effects of two controlled fat- or carbohydrate-restricted
 diets and an outpatient weight loss program on blood and brain chemical composition, weight
 loss (fat and lean body mass), and regional brain activity in lean and obese individuals.

 Eligibility:

 - Healthy individuals between 18 and 45 years of age who are either lean (body mass index
 between 18.5 kg/m(2) and 25 kg/m(2)) or obese (body mass index above 30.0 kg/m(2), weight
 less than 350 pounds) and are right-handed.

 Design:

 -  Lean participants: Participants will be screened with a medical history, physical
 examination, blood and urine tests, and weight maintenance observations (food diaries
 and physical activity monitors). For the scanning visit, participants will receive
 balanced meals from the National Institutes of Health to consume for 2 days before the
 visit. During the scanning visit, participants will continue to eat the weight
 maintenance diet, complete questionnaires, and have a series of imaging studies
 (including positron emission tomography and magnetic resonance imaging tests) to
 evaluate brain response to food and other stimuli.

 -  Obese participants: Participants will be screened with a medical history, physical
 examination, blood and urine tests, and weight maintenance observations (food diaries
 and physical activity monitors). During the first inpatient visit, obese participants
 will eat a weight-maintenance diet for 5 days to establish baseline measurements. After
 several days of eating a weight-maintenance diet, 20 obese adult volunteers (BMI above
 30 kg/m2) will be admitted to the metabolic clinical research unit (MCRU) and, after 5
 additional days of the baseline diet, their diets will be modified to result in either
 85% reduction of the baseline dietary fat or a 60% reduction of the baseline dietary
 carbohydrate for the next 6 days. These diet modifications produce an equivalent caloric
 reduction. The primary outcome measurements will be changes of metabolism, brain reward
 circuitry and regional brain activity in response to food stimuli measured during the
 baseline and reduced calorie diet phases. Immediately following each controlled diet, we
 will measure 3 days of ad-libitum food intake using a computerized vending machine
 system. The subjects will return to the MCRU after a 2-10 week washout period to receive
 the opposite reduced calorie diet. Twenty control subjects with normal body weight (BMI
 between 18.5 - 25 kg/m2) will have measurements of brain reward circuitry and regional
 brain activity in response to food stimuli while on a balanced, weight-maintenance diet.
 Immediately following the second in-patient visit, all of the obese subjects will be
 assigned to a 12 week out-patient weight loss program with the goal of achieving at
 least 5% weight loss. We will investigate the relationship between short-term fat
 imbalances measured during the in-patient phases, and the body weight and fat changes
 during the weight loss program. We will evaluate the effects of weight loss on
 metabolism, brain reward circuitry, and regional brain activity in response to food
 stimuli. Finally, if the subjects are available for long-term follow-up, then we will
 investigate their metabolic phenotype, brain reward circuitry, and regional brain
 activity in response to food stimuli yearly over the subsequent 5 years following the
 weight loss intervention. This study will result in an improved understanding of the
 physiological mechanisms that sense and respond to negative energy balance acutely,
 after several weeks, and after several years, and may eventually lead to increased
 long-term success of obesity treatment.
-  INCLUSION CRITERIA:

 -  Age 18-45 years, male or female

 -  Body mass less than 350 lbs. (max. weight dictated by table limit for functional
 magnetic resonance imaging (fMRI) scanner) when acquisition of large bore fMRI is
 complete, max. wt. limit will increase to 400 lbs.

 -  Weight stable (less than plus or minus 5 kg over past 6 months)

 -  Body mass index greater than or equal to 30.0 kg/m(2)

 -  Premenopausal (women only)

 -  Healthy, as determined by medical history and laboratory tests

 -  Able to complete daily bouts of walking at a moderate rate

 -  Written informed consent

 EXCLUSION CRITERIA:

 -  Body mass greater than 350 lbs. (max. weight dictated by table limit for fMRI scanner)
 when acquisition of large bore fMRI is complete, max. wt. limit will increase to 400
 lbs.

 -  BMI less than 30.0 kg/m(2)

 -  Evidence of metabolic or cardiovascular disease, or disease that may influence
 metabolism (e.g. cancer, diabetes, thyroid disease)

 -  Taking any prescription medication (except birth control) or other drug that may
 influence metabolism (e.g. diet/weight-loss medication)

 -  Hematocrit less than 34% (women only)

 -  Hematocrit less than 40% (men only)

 -  Pregnancy, lactation (women only)

 -  Allergy to lidocaine or ethanol

 -  Participating in a regular exercise program (greater than 2h/week of vigorous
 activity)

 -  Caffeine consumption greater than 150 mg/day (will be clamped at baseline intake
 during study)

 -  Regular use of alcohol (greater than 2 drinks per day), tobacco (smoking or chewing),
 amphetamines, cocaine, heroin, or marijuana over past 6 months

 -  Past or present history of eating disorder (including binge eating) or psychiatric
 disease

 -  Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, multiple food
 allergies)

 -  Are claustrophobic to a degree that they would feel uncomfortable in the MRI machine.

 -  Having any metal in their body (for example, pacemakers, metallic prostheses such as
 cochlear implants or heart valves, shrapnel fragments, etc.).

 -  Left-handedness

 -  Non-native English speakers

 -  Volunteers unwilling or unable to give informed consent

 Control Subjects

 INCLUSION CRITERIA:

 -  Age 18-45 years, male or female

 -  18.5 kg/m(2) less than BMI less than 25.0 kg/m(2)

 -  Weight stable (less than plus or minus 5 kg over past 6 months)

 -  Premenopausal (women only)

 -  Healthy, as determined by medical history and laboratory tests

 -  Written informed consent

 EXCLUSION CRITERIA:

 -  BMI less than 18.5 or greater than 25.0 kg/m(2)

 -  Evidence of metabolic or cardiovascular disease, or disease that may influence
 metabolism (e.g. cancer or diabetes)

 -  Taking any prescription medication (except birth control) or other drug that may
 influence metabolism (e.g. diet/weight-loss medication)

 -  Hyperlipidemia (fasting plasma triglyceride concentration greater than 150 mg/dl)

 -  Hematocrit less than 34% (women only)

 -  Hematocrit less than 40% (men only)

 -  Pregnancy, lactation (women only)

 -  Participating in a regular exercise program (greater than 2h/week of vigorous
 activity)

 -  Caffeine consumption greater than 150 mg/day

 -  Regular use of alcohol (greater than 2 drinks per day), tobacco (smoking or chewing),
 amphetamines, cocaine, heroin, or marijuana over the past 6 months

 -  Past or present history of eating disorder (including binge eating) or psychiatric
 disease

 -  Volunteers with strict dietary concerns (e.g vegetarian or kosher diet, multiple food
 allergies)

 -  Are claustrophobic to a degree that they would feel uncomfortable in the MRI machine.

 -  Having any metal in their body (for example, pacemakers, metallic prostheses such as
 cochlear implants or heart valves, shrapnel fragments, etc.).

 -  Left-handedness

 -  Non-native English speakers

 -  Volunteers unwilling or unable to give informed consent