Water Deprivation Protocol

Study Description:

The percentage of people with overweight / obesity in the United States has reached very high levels, with 65% of adults over the age of 20 being overweight. Recently, there have been a number of advances in our understanding of the underlying causes of obesity, including greater understanding of both the effects of the environment and effects that are hereditary (i.e., genetic).

One area in which obese versus lean individuals may be different is how their bodies handle water balance and thirst. Studies done in animals suggest that individuals with greater body fat may tolerate periods without water better than lean animals. Thus, at least in animals, others have found a link between ability to tolerate periods without water and increased body weight.

We are studying whether the ability to tolerate periods without water and ability to feel thirst might differ in lean versus obese individuals. To do so, we will ask lean and obese individuals to undergo tests that include a period of approximately 24 hours without drinking any water, and on a separate day a shorter period of an intravenous high salt solution infusion. We will be looking at how the ability to withstand thirst (dehydration), subsequent water intake (rehydration), changes in hormone levels during these periods, and behavioral and physiological responses to thirst and rehydration differ in lean versus obese individuals. We hope that the data gathered from this study will give us more information about important differences in how water balance is regulated in lean versus obese individuals. Understanding these questions may provide new insights into differences between lean and obese individuals.

Objectives:

Primary Objective: to determine if obese versus lean individuals differ in their response (as measured by objective measurement of water intake) to water deprivation and hyperosmolality (dehydration).

Secondary Objective: to determine if during these challenges there are differences in hormonal responses to dehydration and subsequent rehydration, and how these changes are related to adiposity and adipose tissue metabolism.

• INCLUSION CRITERIA:
• Male.
• Age 18-50 yrs to minimize hormonal influences on thirst perception in aging men.
• BMI<25 kg/m^2 for the lean group and BMI >=35 kg/m^2 for obese group (but weigh less than 350 pounds to accommodate the DXA scanner) for the obese group.
• Healthy, as determined by medical history and physical examination, without the exclusions listed below:

Exclusion criteria

History or Clinical Manifestation of:

• Currently smoking
• Any medications
• Weight <50kg (as the blood withdrawal limit would be exceeded)
• Hemoglobin concentration < 12mg/dl on screening labs
• Type 1 or type 2 diabetes (according to World Health Organization diagnostic criteria (59))
• Endocrine disorders (Cushing's disease, pituitary diseases, hypo- or hyperthyroidism, diabetes insipidus, SIADH)
• Hypertension as diagnosed and treated by an outside physician or by sitting blood pressure measurement, using an appropriate cuff, >140/90 mmHg on two or more occasions
• Fasting triglyceride concentrations >= 500 mg/dl
• Cardiovascular disease, including coronary heart disease, heart failure, arrhythmias and peripheral arterial disease
• Liver disease, including cirrhosis, active hepatitis B or C and AST or ALT >= 3x normal
• Renal disease, as defined by serum creatinine concentrations >= 1.5 mg/dl and / or proteinuria >300 mg/day (200 (micro)g/min)
• Central nervous system disease, including previous history of cerebrovascular accidents, dementia, and neurodegenerative disorders
• Cancer requiring treatment in the past five years, except for non-melanoma skin cancers or cancers that have been clearly cured or, in the opinion of the investigator, carry an excellent prognosis
• Infectious diseases such as active tuberculosis, HIV (by self report), chronic coccidioidomycoses or other chronic infections
• Alcohol and/or current use of drugs (more than 2 drinks per day and regular use of drugs such as amphetamines, cocaine, heroin, or marijuana)
• Psychiatric conditions or behaviors that would be incompatible with safe and successful participation in this study, including claustrophobia and eating disorders such as anorexia or bulimia nervosa

All subjects will be fully informed of the aim, nature, and risks of the study prior to giving written informed consent. Subjects will also be specifically advised that the results of testing for drug usage will be filed in the medical record and would, therefore, be available as part of this record.