Changes in extracellular osmolality, and thus in the cellular hydration sta
te, appear to directly influence cell metabolism. The metabolic changes ass
ociated with cell swelling are inhibition of glycogenolysis, glycolysis, an
d proteolysis. Recent studies in our laboratory demonstrated diminished who
re-body protein breakdown in humans during an acute hypoosmolar state. Beca
use of the close interrelationship between carbohydrate and fat metabolism
we speculated that adipose tissue lipolysis and fatty acid oxidation are re
gulated by changes in extracellular osmolality. Therefore, we investigated
the effect of artificially induced hypoosmolality on whole-body lipolysis a
nd fat oxidation in seven healthy young men. Hypoosmolality was induced by
intravenous administration of desmopressin, liberal ingestion of water, and
infusion of hypotonic (0.45%) saline solution. Lipolysis was assessed by a
stable-isotope method (2-[C-13]-glycerol infusion). The glycerol rate of a
ppearance (Ra), reflecting whole-body lipolysis, was higher under hypoosmol
ar compared with isoosmolar conditions (2.35 +/- 0.40 v 1.68 +/- 0.21 mu mo
l/kg/min, P = .03). This was even more pronounced when lipolysis was suppre
ssed during hyperinsulinemia and euglycemic clamping (0.90 +/- 0.08 v 0.61
+/- 0.03 mu mol/kg/min, P = .002). However, plasma free fatty acid (FFA), g
lycerol, ketone body, insulin, and glucagon concentrations and carbohydrate
and lipid oxidation measured by indirect calorimetry were not significantl
y altered by hypoosmolality. Plasma norepinephrine concentrations were lowe
r under hypoosmolar conditions (P < .01 v control), In conclusion, hypoosmo
larity in vivo results in increased whole-body lipolysis, which is not due
to changes in major lipolysis regulating hormones. Copyright (C) 1999 by W.
B. Saunders Company.