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 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.
Leibowitz
S F
SF
The Rockefeller University, 1230 York Ave., New York, NY, USA. leibow@rockefeller.edu
Chang
G-Q
GQ
Dourmashkin
J T
JT
Yun
R
R
Julien
C
C
Pamy
P P
PP
D000818:Animals; D001835:Body Weight; D004041:Dietary Fats / Q000378:metabolism*; D004198:Disease Susceptibility / Q000503:physiopathology; D007113:Immunity, Innate; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D019518:Postprandial Period; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*
D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D014280:Triglycerides