Impaired Adipocyte Lipolysis in Nonobese Women with the Polycystic Ovary Syndrome: A Possible Link to Insulin Resistance?1
Ingvar Ek,
Peter Arner,
Agneta Bergqvist,
Kjell Carlström and
Hans Wahrenberg
Departments of Medicine and Gynecology and Obstetrics, and the
Research Center, Huddinge University Hospital, Karolinska Institute,
Huddinge, Sweden
Address all correspondence and requests for reprints to: Hans Wahrenberg, M.D., Division of Endocrinology and Metabolism, Department of Medicine M63, Huddinge Hospital, Karolinska Institute, S-141 86 Huddinge, Sweden.
The polycystic ovary syndrome (PCOS) is the most common hyperandrogenic
disorderamong women and is characterized by metabolic and
cardiovascularaberrations similar to those seen in the so-called
insulin resistancesyndrome. The regulation of lipolysis was
investigated in isolatedabdominal sc adipocytes from 10 nonobese women
with PCOS andin 11 age- and body mass index-matched healthy women.
EightPCOS women were reinvestigated after 3 months of treatment with
combinedoral contraceptives containing ethinyl estradiol and
norethisterone,which normalized hyperandrogenicity. The PCOS women
showed amarked resistance to the lipolytic effect of noradrenaline due
todefects at two different levels in the lipolytic cascade: first,a
7-fold reduction in sensitivity to the ß2-selective
agonistterbutaline (P < 0.005), which could be
ascribed to a 50%lower ß2-adrenoceptor density
(P < 0.02) as determinedwith radioligand binding;
there was no difference with regardto dobutamine (ß1) or
clonidine (2-sensitivity) or
ß1-adrenoceptordensity; second, the maximum lipolytic
response was also 35%lower (P < 0.02) in the
PCOS women compared to that in thehealthy women. This was seen with
all ß-adrenergic agonistsand the postreceptor-acting agents
forskolin (activating adenylylcyclase) and dibutyryl cAMP (activating
protein kinase). Neitherß2-adrenoceptor sensitivity or
density nor the reducedlipolytic responsiveness was restored by 3
months of oral contraceptivestreatment. The results indicate the
existence of a marked impairmentof catecholamine-induced lipolysis in
nonobese PCOS women displayingearly features of the insulin resistance
syndrome due to multiplelipolysis defects as a lower
ß2-adrenoceptor density andreduced function of the
protein kinase, hormone-sensitive lipasecomplex. These lipolysis
defects are identical to those observedin the insulin resistance
(metabolic) syndrome and could bea primary pathogenic mechanism for
the development of thesedisorders.
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2-sensitivity) or
ß1-adrenoceptor density; second, the maximum lipolytic
response was also 35% lower (P < 0.02) in the
PCOS women compared to that in the healthy women. This was seen with
all ß-adrenergic agonists and the postreceptor-acting agents
forskolin (activating adenylyl cyclase) and dibutyryl cAMP (activating
protein kinase). Neither ß2-adrenoceptor sensitivity or
density nor the reduced lipolytic responsiveness was restored by 3
months of oral contraceptives treatment. The results indicate the
existence of a marked impairment of catecholamine-induced lipolysis in
nonobese PCOS women displaying early features of the insulin resistance
syndrome due to multiple lipolysis defects as a lower
ß2-adrenoceptor density and reduced function of the
protein kinase, hormone-sensitive lipase complex. These lipolysis
defects are identical to those observed in the insulin resistance
(metabolic) syndrome and could be a primary pathogenic mechanism for
the development of these disorders. 
