Differential modulation of arcuate nucleus and mesolimbic gene expression levels by central leptin in rats on short-term high-fat high-sugar diet

José K van den Heuvel; Leslie Eggels; Eric Fliers; Andries Kalsbeek; Roger A H Adan; Susanne E la Fleur

doi:10.1371/journal.pone.0087729

Differential modulation of arcuate nucleus and mesolimbic gene expression levels by central leptin in rats on short-term high-fat high-sugar diet

PLoS One. 2014 Jan 31;9(1):e87729. doi: 10.1371/journal.pone.0087729. eCollection 2014.

Authors

José K van den Heuvel¹, Leslie Eggels¹, Eric Fliers¹, Andries Kalsbeek², Roger A H Adan³, Susanne E la Fleur¹

Affiliations

¹ Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
² Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.
³ Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, Utrecht, The Netherlands.

Abstract

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.

Design and 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.

Conclusion: 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arcuate Nucleus of Hypothalamus / metabolism*
Dietary Carbohydrates / pharmacology*
Dietary Fats / pharmacology*
Feeding Behavior / drug effects
Gene Expression Regulation / drug effects*
Leptin / metabolism
Leptin / pharmacology*
Male
Nerve Tissue Proteins / biosynthesis*
Rats
Rats, Wistar

Substances

Dietary Carbohydrates
Dietary Fats
Leptin
Nerve Tissue Proteins

Grants and funding

This research was supported by the Netherlands Organization for Scientific Research (ZonMw VIDI 91796331); LE was supported by a grant from ZonMw (TOP 91207036). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.