# ADIPOSE DISTRIBUTION AND ADRENERGIC MECHANISMS IN AGING

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1991 · $198,184

## Abstract

Many of the detrimental metabolic consequences of obesity are closely
related to a central or intraabdominal (IA) distribution of fat.  Aging
is associated with increased "fatness', increased central/IA adiposity
and frequent metabolic abnormalities similar to those observed in younger
obese patients.  The regulation of fat cell size in specific fat depots
and thus the distribution of adiposity in the elderly has not been
previously investigated.  Of the important regulators of fat cell size,
the sympathetic nervous system (SNS) activity, may play the most critical
role.  There is strong evidence that differential adrenergic
responsiveness (beta vs alpha2) in specific fat depots plays an important
role in the regulation of fat cell lipolysis.  Furthermore, there is some
in vitro evidence that adipose tissue lipoprotein lipase (AT-LPL), the
rate limiting enzyme for triglyceride (TG) storage, is also regulated by
adrenergic mechanisms in a manner inverse to lipolysis.

Both young obese and elderly subjects appear to have a chronic increase
in SNS activity.  We hypothesize that this chronic increase in adrenergic
tone produces a desensitization of beta, but not alpha2, adrenergic
mechanisms in fat cells.  The fat cells in which this change would
produce the greatest impact are those with the highest beta
responsiveness under normal conditions (Central/IA depots, see Appendix,
Fig 1).  Beta adrenergic desensitization would reduce hormone sensitive
lipase (HSL) mediated lipolysis and possibly increase AT-LPL mediated TG
storage (see Appendix, Fig 2) preferentially in these normally very beta
responsive central/IA depots, thus promoting an accumulation of fat.  We
hypothesize that with weight loss the associated decline in SNS activity
will reverse the beta adrenergic desensitization and cause a preferential
loss of central/IA adiposity.

In this proposal we will prospectively study central (abdominal) and
peripheral (gluteal) fat depots in obese elderly subjects before and
after dietary weight loss in order to attempt to elucidate the mechanisms
by which increased SNS activity may regulate fat distribution.  We will
measure: 1) SNS activity as reflected by both arterialized plasma
catecholamine concentrations and nonepinephrine (NE) kinetics; 2) fat
cell (and peripheral blood cell) beta and alpha2 adrenergic receptor
concentrations and activity (including adenylate cyclase activity); 3)
adrenergically stimulated fat cell lipolytic rates; 4) AT-LPL
activity,mass and messenger RNA (m-RNA); 5) fat cell size on frozen
section; 6) insulin sensitivity using the Bergman minimal model; and 7)
lipoprotein profiles.

## Key facts

- **NIH application ID:** 3120398
- **Project number:** 1R01AG008673-01A2
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** Robert S Schwartz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $198,184
- **Award type:** 1
- **Project period:** 1991-05-01 → 1994-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120398

## Citation

> US National Institutes of Health, RePORTER application 3120398, ADIPOSE DISTRIBUTION AND ADRENERGIC MECHANISMS IN AGING (1R01AG008673-01A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120398. Licensed CC0.

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