Adrenergic control of proteolysis in brown adipocytes
Date
2002
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Masters
Abstract
Brown adipose tissue (BAT) is a sympathetically innervated tissue
involved in control of thermoregulation and energy balance. BAT growth and/or
atrophy occur in response to the need for energy dissipation. Fasting, deacclimation,
and lactation result in tissue atrophy by loss of cells, mitochondrial proteins, and
uncoupling protein 1 (UCP1), the molecular basis for thermogenesis. The overall
objective is to gain a better understanding of the control and the mechanisms
underlying BAT atrophy. Specific objectives are: (1) whether in vivo patterns of BAT
atrophy can be reproduced in culture. (2) whether the loss of mitochondrial proteins is
due to lysosomal proteolysis or proteolysis within mitochondria, under adrenergic
influence. Mouse pre-adipocytes in culture differentiated to brown adipocytes.
Increased expression of UCP1 was induced by norepinephrine (NE). NE was then
removed and the pattern of change in thermogenic capacity evaluated. The number of
cells and their protein content did not change, whereas the cell UCP1 content was
decreased. Expression of cathepsin D (a lysosomal protease) was differentiation-dependent,
but was not affected by NE. Direct estimates of turnover rates of UCP1 as
well as mitochondrial translation products indicated that NE reduces the degradation
of mitochondrial proteins as a whole. Addition of autophagic blockers reduced the
loss of UCP1 upon NE removal. Therefore, in vitro cultures of brown adipocytes
mimic some aspects of brown fat atrophy seen in vivo. Brown pre-adipocytes gain a
large capacity for lysosomal protein degradation during differentiation. The activity
of lysosomal proteases seems under the inhibitory control of NE, as its removal
causes net loss of UCP1 preventable by inhibitors of autophagy.
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Citation
Degree
Master of Science (M.Sc.)
Department
Physiology
Program
Physiology