Our previous studies have shown that the dopaminergic D1 receptor agonist
SKF38393 (SKF) plus the D2 receptor agonist
bromocriptine (BC) act synergistically to reduce
obesity in obese C57BL/6J (ob/ob) mice. The present study investigated the effects of this combination on
dyslipidemia in ob/ob mice. Female ob/ob mice were treated daily with vehicle or SKF (20 mg/kg
body weight [BW]) plus BC (16 mg/kg BW [BC/SKF]) for 14 days. The animals were then used for the characterization of plasma
lipoprotein profiles, hepatic
triacylglycerol synthesis and secretion, adipocyte lipolysis, adipose and muscle
lipoprotein lipase (LPL) activity, and muscle
triglyceride (TG) content. The treatment significantly reduced plasma
glucose 54%, TG 41%,
cholesterol 21%,
phospholipid 20%, and
free fatty acid (FFA) 36% (P < .01). Hepatic
triacylglycerol synthesis was 55% lower in treated mice versus control mice (P < .01). The cell size of isolated adipocytes was significantly reduced (41%) by treatment. LPL activity was increased in soleus skeletal muscle (25%, P < .05) but was sharply reduced in adipose tissue (91%, P < .01) in treated versus control mice. The TG content of hindlimb muscle was about 49% lower in treated versus control mice (P < .05). The basal and
isoproterenol-stimulated lipolytic rate was decreased (approximately 53%) in adipocytes from treated animals compared with the control (P < .01). In conclusion, BC/SKF normalized the
hypertriglyceridemia likely via its simultaneous antilipogenic action in liver tissue and antilipolytic action in adipose tissue. Decreased plasma flux of FFA partially contributed to the reduced hepatic lipogenesis, plasma
very-low-density lipoprotein (VLDL)-TG, and TG in skeletal muscle. The above-described effects of BC/SKF treatment are largely independent of its effect to normalize
hyperphagia in ob/ob mice.