Leptin secretion after a high-fat meal in normal-weight rats: strong predictor of long-term body fat accrual on a high-fat diet

The Rockefeller University, New York, New York Submitted 27 December 2004 ; accepted in final form 12 September 2005 The objective of this study was to investigate meal-related endocrine changes that permit one to identify Sprague-Dawley rats at normal weight that are prone (OP) vs. resistant (OR) to obesity. In blood collected via chronic cardiac catheters, a 2-h high-fat meal (HFM, 50% fat, 40 kcal) at dark onset caused a significant increase in leptin, insulin, and triglycerides compared with premeal levels. Similar to patterns in already obese compared with lean rats on a high-fat diet, these meal-induced endocrine changes in normal-weight rats on lab chow were almost twofold larger in OP rats that, compared with OR rats, subsequently accumulated 100% more fat mass on a chronic high-fat diet. These exaggerated endocrine changes were similarly observed in blood collected using a simpler tail vein puncture procedure. In three separate experiments, the HFM-induced rise in leptin was found to be the strongest, positive correlate ( r = +0.58, +0.62 and +0.64) of long-term body fat accrual. The lowest (2–5 ng/ml) vs. highest (6–9 ng/ml) scores for this post-HFM leptin measurement identified distinct OR and OP subgroups, respectively, when they were similar in body weight (340–350 g), premeal leptin (2.6–3.4 ng/ml), and meal size (40 kcal). Subsequent tests in these normal-weight OP rats revealed a distinct characteristic compared with OR rats, namely, exaggerated HFM-induced rise in expression of the orexigenic peptide galanin in the paraventricular nucleus. Thus, with this HFM-induced leptin measurement, OP rats can be identified while still at normal weight and then investigated for mechanisms that contribute to their excessive body fat accrual on a high-fat diet. insulin; triglycerides; galanin; neuropeptide Y Address for reprint requests and other correspondence: S. F. Leibowitz, The Rockefeller University, 1230 York Ave., New York, NY (e-mail: leibow{at}rockefeller.edu )