Aging, Exercise, and Hormonal Influences of Fat Metabolism
Condition: Cardiovascular Disease
MeSH terms: Cardiovascular Diseases
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether exercise alters the way in which the body
      stores and breaks down fat. A second objective is to evaluate how these effects are
      influenced by your age and gender. These studies are important because aging, male gender,
      and menopause are associated with an increased storage of abdominal fat which is frequently
      accompanied by diabetes, a high blood cholesterol level, high blood pressure and greater
      risks of heart attack, stroke, and death. Increasing evidence suggests that these
      abnormalities and many other effects of aging may be partly due to lack of exercise.
    

Detailed description: 
      The physiologic cause(s) of the age-related increase in total body and abdominal fat mass are
      not well-understood. The purpose of this study is to determine whether aging is associated
      with decreased whole body lipolytic and other metabolic responses to epinephrine and insulin,
      whether these responses may be augmented by exercise training or in older women by estrogen
      administration and to investigate whether such metabolic changes are related to reductions in
      abdominal adiposity. Our objectives in this project are as follows: (1) to characterize age
      and gender differences in lipolysis and other aspects of metabolism at rest and during graded
      dose epinephrine infusion with or without a pancreatic islet clamp in healthy non-obese men
      and women aged 20-40 and 55-75 years, (2) to evaluate relationships between metabolic
      responses to epinephrine or insulin and portally and nonportally-drained visceral and
      subcutaneous adipose tissue mass in these individuals, (3) to delineate the effects of acute
      and chronic exercise on lipolytic and other metabolic responses to epinephrine and insulin
      and on adipose tissue distribution in healthy younger and older men and women, and (4) to
      investigate whether 7 days and 12 months or estrogen and cyclic progesterone replacement
      therapy or placebo in healthy 55-75 year old women alter lipolytic and other metabolic
      responses to epinephrine and insulin and adipose tissue distribution.

      The rates of lipolysis, oxygen uptake, fat and carbohydrate oxidation, and total
      triglyceride-free fatty acid (FFA) substrate cycling will be determined by indirect
      calorimetry and by gas chromatography-mass spectrometric analyses of blood samples obtained
      during infusions of the stable isotope tracers [D5] glycerol and [1 -13C] palmitate in the
      baseline state, during a pancreatic islet clamp in half of all male and female participants,
      and in all participants during a subsequent 4-stage graded dose epinephrine infusion. These
      data will be expressed in relation to total body wieght, fat mass, and fat-free mass,
      assessed from measurements of body density made by hydrostatic weighing. Adipose tissue
      distribution will be characterized by determination of the cross-sectional area and volume of
      portally and nonportally-drained visceral and subcutaneous fat deposits identified by
      radiographic density criteria on computed tomographic scans obtained at the level of the
      nipple, umbilicus, gluteal region, and midthigh. Insulin action on glucose disposal will be
      assessed during a hyperinsulinemic euglycemic clamp. Age and gender differences and their
      interactions with exercise and the plasma epinephrine concentration in the baseline state and
      during submaximally and maximally stimulating rates of epinephrine infustion will be
      evaluated by analysis of variance and covariance. Relationships between effects of estrogen
      treatment or exercise of adipose tissue distribution and responses to epinephrine and insulin
      will be assessed by multiple regression analysis.

      We hypothesize that increased age will be associated with lower epinephrine-induced rates of
      lipolysis, fat oxidation, and triglyceride-FFA substrate cycling and decreased insulin action
      in both men and women when expressed in relation to total fat mass. We further hypothesize
      that these age-related differences will be at least partly ameliorated by exercise training
      and by treatment with estrogen in conjunction with a decrease in visceral abdominal and total
      body adiposity.
    

Intervention name(s): exercise
Intervention type(s): Procedure
Primary purpose: Treatment
Keywords: Adipose tissue; Aging; Exercise; Lipolysis; Estrogens