RELATIONSHIPS OF PLASMA LEPTIN LEVELS TO CHANGES IN PLASMA-FREE FATTY-ACIDS IN WOMEN WHO ARE LEAN AND WOMEN WHO ARE ABDOMINALLY OBESE

Regulation of leptin production by the hormonal and metabolic milieu i s poorly understood, Because abdominal obesity is commonly associated with elevated plasma free fatty acid (FFA) flux, we examined the effec ts of augmenting FFA on plasma leptin levels in women who were lean an d of suppressing FFA in women with abdominal obesity, In study 1, nine subjects who were lean, after a 12-hour overnight fast, received eith er intravenous saline or Intralipid plus heparin to increase the plasm a FFA. concentration to approximately 1000 mu mol/L. After 3 hours of additional fasting, subjects underwent 3-hour hyperglycemic clamps, In study 2, seven subjects with abdominal obesity were evaluated by a si milar protocol, but lipolysis and plasma FFA flux were instead maximal ly suppressed by acipimox. In the individuals who were lean, leptin le vels were unchanged during clamping, Increasing plasma FFA reduced pla sma leptin from 7.66 +/- 0.66 to 7.05 +/- 0.66 (p=0.03), but 3 hours o f hyperglycemia plus hyperinsulinemia had no additional effect on lept in levels (7.15 +/- 0.71). Basal leptin levels, 4-fold higher in the s ubjects with obesity, were reduced from 34.6 +/- 2.4 mu g/L to 32.3 +/ - 1.1 mu g/L (p=0.004) during the clamp period, When plasma FFA flux w as suppressed, however, plasma leptin levels after clamped hyperglycem ia/hyperinsulinemia were increased to 38.9 +/- 1.2 mu g/L (p=0.014 vs, time 0 and 0.001 vs, saline protocol), Changes in leptin concentratio ns are not correlated with changes in FFA. These results suggest that plasma FFA concentration does not regulate plasma leptin levels in bas al, extended fasting, or hyperglycemic/hyperinsulinemic states.