Differential modulation of arcuate nucleus and mesolimbic gene expression levels by central leptin in rats on short-term high-fat high-sugar diet.
OBJECTIVE
Leptin resistance is a common hallmark of obesity. Rats on a free-choice high-fat high-sugar (fcHFHS) diet are resistant to peripherally administered leptin. The aim of this study was to investigate feeding responses to central leptin as well as the associated changes in mRNA levels in hypothalamic and mesolimbic brain areas.


METHODS
Rats on a CHOW or fcHFHS diet for 8 days received leptin or vehicle intracerebro(lateral)ventricularly (ICV) and food intake was measured 5 h and 24 h later. Four days later, rats were sacrificed after ICV leptin or vehicle and mRNA levels were quantified for hypothalamic pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) and for preproenkephalin (ppENK) in nucleus accumbens and tyrosine hydroxylase (TH) in ventral tegmental area (VTA).


RESULTS
ICV leptin decreased caloric intake both in CHOW and fcHFHS rats. In fcHFHS, leptin preferentially decreased chow and fat intake. Leptin increased POMC and decreased NPY mRNA in CHOW, but not in fcHFHS rats. In CHOW rats, leptin had no effect on ppENK mRNA and decreased TH mRNA. In fcHFHS, leptin decreased ppENK mRNA and increased TH mRNA.


CONCLUSIONS
Despite peripheral and arcuate leptin resistance, central leptin suppresses feeding in fcHFHS rats. As the VTA and nucleus accumbens are still responsive to leptin, these brain areas may therefore, at least partly, account for the leptin-induced feeding suppression in rats on a fcHFHS diet.
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
José K
JK
van den Heuvel
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Leslie
L
Eggels
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Eric
E
Fliers
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.
Andries
A
Kalsbeek
Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Roger A H
RA
Adan
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Susanne E
SE
la Fleur
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D020738:Leptin; D009419:Nerve Tissue Proteins